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Extracellular vesicles (EVs), a class of heterogeneous membrane vesicles, are generally divided into exosomes and microvesicles on basis of their origination from the endosomal membrane or the plasma membrane, respectively. EV-mediated bidirectional communication among various cell types supports cancer cell growth and metastasis. EVs derived from different cell types and status have been shown to have distinct RNA profiles, comprising messenger RNAs and non-coding RNAs (ncRNAs). Recently, ncRNAs have attracted great interests in the field of EV-RNA research, and growing numbers of ncRNAs ranging from microRNAs to long ncRNAs have been investigated to reveal their specific functions and underlying mechanisms in the tumor microenvironment and premetastatic niches. Emerging evidence has indicated that EV-RNAs are essential functional cargoes in modulating hallmarks of cancers and in reciprocal crosstalk within tumor cells and between tumor and stromal cells over short and long distance, thereby regulating the initiation, development and progression of cancers. In this review, we discuss current findings regarding EV biogenesis, release and interaction with target cells as well as EV-RNA sorting, and highlight biological roles and molecular mechanisms of EV-ncRNAs in cancer biology.

Long non-coding RNAs (lncRNAs) are extensively intricate in the tumorigenesis and metastasis of various cancer types. Nevertheless, the detailed molecular mechanisms of lncRNA in non-small cell lung cancer (NSCLC) still remain mainly undetermined. qPCR was performed to verify LINC00301 expression in NSCLC clinical specimens or cell lines. Fluorescence in situ hybridization (FISH) was conducted to identify the localization of LINC00301 in NSCLC cells. Chromatin immunoprecipitation (ChIP) was subjected to validate the binding activity between FOXC1 and LINC00301 promoters. RNA immunoprecipitation (RIP) was performed to explore the binding activity between LINC00301 and EZH2. RNA pull-down followed by dot-blot, protein domain mapping, and RNA electrophoresis mobility shift assay (EMSA) were conducted to identify the detailed binding regions between LINC00301 and EZH2. Alpha assay was conducted to quantitatively assess the interaction between LINC00301 and EZH2. LINC00301 is highly expressed in NSCLC and closely corelated to its prognosis by analyzing the relationship between differentially expressed lncRNAs and prognosis in NSCLC samples. in vitro and in vivo experiments revealed that LINC00301 facilitates cell proliferation, releases NSCLC cell cycle arrest, promotes cell migration and invasion, and suppresses cell apoptosis in NSCLC. In addition, LINC00301 increases regulatory T cell (Treg) while decreases CD8+ T cell population in LA-4/SLN-205-derived tumors through targeting TGF-β. The transcription factor FOXC1 mediates LINC00301 expression in NSCLC. Bioinformatics prediction and in vitro experiments indicated that LINC00301 (83–123 nucleotide [nt]) can directly bind to the enhancer of zeste homolog 2 (EZH2) (612–727 amino acid [aa]) to promote H3K27me3 at the ELL protein-associated factor 2 (EAF2) promoter. EAF2 directly binds and stabilizes von Hippel–Lindau protein (pVHL), so downregulated EAF2 augments hypoxia-inducible factor 1 α (HIF1α) expression by regulating pVHL in NSCLC cells. Moreover, we also found that LINC00301 could function as a competing endogenous RNA (ceRNA) against miR-1276 to expedite HIF1α expression in the cytoplasm of NSCLC cells. In summary, our present research revealed the oncogenic roles of LINC00301 in clinical specimens as well as cellular and animal experiments, illustrating the potential roles and mechanisms of the FOXC1/LINC00301/EZH2/EAF2/pVHL/HIF1α and FOXC1/LINC00301/miR-1276/HIF1α pathways, which provides novel insights and potential theraputic targets to NSCLC.

miRNAs are a class of single-stranded noncoding RNAs, which have no coding potential, but modulate many molecular mechanisms including cancer pathogenesis. miRNAs participate in cell proliferation, differentiation, apoptosis, as well as carcinogenesis or cancer progression, and their involvement in lung cancer has been recently shown. They are suggested to have bidirectional functions on important cancer-related genes so as to enhance or attenuate tumor genesis. Epithelial–mesenchymal transition (EMT) is a fundamental process which contributes to integrity of organogenesis and tissue differentiation as well as tissue repair, organ fibrosis and the progression of carcinoma, and several miRNAs were suggested to form the network regulating EMT in lung cancer, among which, miR-200 family members (miR-200a, miR-200b, miR-200c, miR-429 and miR-141) play crucial roles in the suppression of EMT.

Ambient air pollutants have been linked to adverse health outcomes, but evidence is still relatively rare in college students. Upper respiratory tract infection (URTI) is a common disease of respiratory system among college students. In this study, we assess the acute effect of air pollution on clinic visits of college students for URTI in Wuhan, China. Data on clinic visits due to URTI were collected from Wuhan University Hospital, meteorological factors (including daily temperature and relative humidity) provided by Wuhan Meteorological Bureau, and air pollutants by Wuhan Environmental Protection Bureau. In the present study, generalized additive model with a quasi-Poisson distribution link function was used to examine the association between ambient air pollutants (fine particulate matter (PM2.5), particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3)) and the daily number of clinic visits of college students for URTI at Wuhan University Hospital in Wuhan, China. In the meantime, the model was adjusted for the confounding effects of long-term trends, seasonality, day of the week, public holidays, vacation, and meteorological factors. The best degrees of free in model were selected based on AIC (Akaike Information Criteria). The effect modification by gender was also examined. A total of 44,499 cases with principal diagnosis of URTI were included from January 1, 2016, to December 31, 2018. In single-pollutant models, the largest increment of URTI visits were found at lag 0 day in single-day lags, and the effect values in cumulative lags were greater than those in single-day lags. PM2.5 (0.74% (95%CI: 0.05, 1.44)) at lag 0 day, PM10 (0.61% (95%CI: 0.12, 1.11)) and O3 (1.01% (95%CI: 0.24, 1.79)) at lag 0–1 days, and SO2 (9.18% (95%CI: 3.27, 15.42)) and NO2 (3.40% (95% CI:1.64, 5.19)) at lag 0–3 days were observed to be strongly and significantly associated with clinic visits for URTI. PM10 and NO2 were almost still significantly associated with URTI after controlling for the other pollutants in our two-pollutant models, where the effect value of SO2 after inclusion of O3 appeared to be the largest and the effects of NO2 were also obvious compared with the other pollutants. Subgroups analysis demonstrated that males were more vulnerable to PM10 and O3, while females seemed more vulnerable to exposure to SO2 and NO2. This study implied that short-term exposure to ambient air pollution was associated with increased risk of URTI among college students at Wuhan University Hospital in Wuhan, China. And gaseous pollutants had more negative health impact than solid pollutants. SO2 and NO2 were the major air pollutants affecting the daily number of clinic visits on URTI, to which females seemed more vulnerable than males.

Objectives In order to identify the clinical characteristics of patients with Corona Virus Disease 2019 (COVID-19) and find out the characteristic effects of 2019 New Coronavirus (SARS-CoV-2) infection on changes in clinical and laboratory data. Patients and methods From January 22 to February 13, 2020, we enrolled consecutive patients with acute respiratory tract symptoms admitted to a hospital (Ezhou, Hubei, China). For different data types t-test, the variables associated with the diagnosis of COVID-19 were compared by chi-square test and u-test, the statistically significant variables (P-valueResults 62 (77.5%) confirmed cases and 18 (22.5%) negative cases were confirmed by SARS-CoV-2 nucleic acid test. Epidemiological investigation and statistical analysis were carried out on the clinical and laboratory data of all suspected cases of COVID-19, the specific indicators were found, and the clinical characteristics of COVID-19 were described. Compared with the patients with negative nucleic acid test, the patients with positive nucleic acid test showed shorter time of onset of symptoms, higher plasma CO2 level, lower eosinophil ratio, lower platelet count and hematocrit, lower serum sodium level, higher serum creatinine, higher blood urea and plasma albumin levels (all PConclusions we argue that the SARS-CoV-2 infection can cause multiple organ damage to the heart, liver, kidney and bone marrow other than lung injury.

Additional file 1. Supplementary Tables S1-S5 and Figs. S1-S13.

Background Long non-coding RNAs (lncRNAs) are extensively intricate in the tumorigenesis and metastasis of various cancer types. Nevertheless, the detailed molecular mechanisms of lncRNA in non-small cell lung cancer (NSCLC) still remain mainly undetermined. Methods qPCR was performed to verify LINC00301 expression in NSCLC clinical specimens or cell lines. Fluorescence in situ hybridization (FISH) was conducted to identify the localization of LINC00301 in NSCLC cells. Chromatin immunoprecipitation (ChIP) was subjected to validate the binding activity between FOXC1 and LINC00301 promoters. RNA immunoprecipitation (RIP) was performed to explore the binding activity between LINC00301 and EZH2. RNA pull-down followed by dot-blot, protein domain mapping, and RNA electrophoresis mobility shift assay (EMSA) were conducted to identify the detailed binding regions between LINC00301 and EZH2. Alpha assay was conducted to quantitatively assess the interaction between LINC00301 and EZH2. Results LINC00301 is highly expressed in NSCLC and closely corelated to its prognosis by analyzing the relationship between differentially expressed lncRNAs and prognosis in NSCLC samples. in vitro and in vivo experiments revealed that LINC00301 facilitates cell proliferation, releases NSCLC cell cycle arrest, promotes cell migration and invasion, and suppresses cell apoptosis in NSCLC. In addition, LINC00301 increases regulatory T cell (Treg) while decreases CD8+ T cell population in LA-4/SLN-205-derived tumors through targeting TGF-β. The transcription factor FOXC1 mediates LINC00301 expression in NSCLC. Bioinformatics prediction and in vitro experiments indicated that LINC00301 (83–123 nucleotide [nt]) can directly bind to the enhancer of zeste homolog 2 (EZH2) (612–727 amino acid [aa]) to promote H3K27me3 at the ELL protein-associated factor 2 (EAF2) promoter. EAF2 directly binds and stabilizes von Hippel–Lindau protein (pVHL), so downregulated EAF2 augments hypoxia-inducible factor 1 α (HIF1α) expression by regulating pVHL in NSCLC cells. Moreover, we also found that LINC00301 could function as a competing endogenous RNA (ceRNA) against miR-1276 to expedite HIF1α expression in the cytoplasm of NSCLC cells. Conclusions In summary, our present research revealed the oncogenic roles of LINC00301 in clinical specimens as well as cellular and animal experiments, illustrating the potential roles and mechanisms of the FOXC1/LINC00301/EZH2/EAF2/pVHL/HIF1α and FOXC1/LINC00301/miR-1276/HIF1α pathways, which provides novel insights and potential theraputic targets to NSCLC.

E2F transcription factors (E2Fs), a group of genes that encode a family of transcription factors, have been identified as being involved in the tumor progression of various cancer types. Increasing experimental evidence indicates that E2Fs are implicated in breast cancer tumorigenesis. However, the diverse expression patterns and prognostic values of eight E2Fs have yet to be analyzed. Herein we investigated the transcriptional and survival data of E2Fs in patients with breast cancer from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, and cBioPortal databases. We found that the expression levels of E2F1–3 and 5–8 were higher in breast cancer tissues than in normal breast tissues, whereas the expression level of E2F4 was lower in the former than in the latter. The expression levels of E2F2, 5, 7, and 8 were correlated with advanced tumor stage. Survival analysis using the Kaplan-Meier Plotter database revealed that the high transcription levels of E2F1–3, 5, 7, and 8 were associated with low relapse-free survival in all of the patients with breast cancer. Conversely, high E2F4 and E2F6 levels predicted high relapse-free survival in these patients. This study implied that E2F1–3, 5, 7, and 8 are potential targets of precision therapy for patients with breast cancer and that E2F4 and 6 are new biomarkers for the prognosis of breast cancer.

Background and Aims Maternal obesity predispose offspring to metabolic disorders and obesity, but the mechanisms are not fully understood, especially during early life. Circular RNA (circRNA) can regulate the expression of target genes through the regulatory pathways of competing endogenous RNA (ceRNA). We hypothesized that the offspring of obese dams exhibit impaired metabolic health through the dysregulated expression of hepatic circRNA. Methods and Results A high-fat diet (HFD) or standard chow diet (CD) were randomized to dams for 12 weeks before mating. Specific diets continued for each dam throughout pregnancy and lactation. Then, lipid metabolic parameters were assessed in dams and female offspring. We performed liver RNA sequencing (RNA-seq) for the offspring of HFD- and CD-dams to comprehensively identify differentially expressed (DE) circRNA and messenger RNA (mRNA). Further, ceRNA networks combining DE circRNA, mRNA, and microRNA were predicted based on MiRanda and TargetScan databases combined with the lipid metabolism-related pathway. As a result, the circRNA_0000660-miR_693-Igfbp1 regulatory pathway was selected from liver and AML12 cell line. Quantitative real-time polymerase chain reaction, dual luciferase reporter gene system, and Small interfering RNA for circRNA_0000660 transfection experiment were applied to validate. Conclusions Our work investigated new mechanisms of the effect of maternal obesity on offspring’s lipid metabolism. Several novel targets were uncovered to reverse the effect.

E2F is a group of genes that encode a family of transcription factors (TFs) in higher eukaryotes and participate in cell cycle regulation and DNA synthesis in mammalian cells. Evidence from cell lines, mouse models, and human tissues indicates that TFs are implicated in lung cancer (LC) tumorigenesis. However, the diverse expression patterns and prognostic values of eight E2Fs have yet to be elucidated. In the current study, we examined the transcriptional and survival data of E2Fs in patients with LC from ONCOMINE, GEPIA, Kaplan-Meier Plotter, and cBioPortal databases. We found that the expression levels of E2F1/2/3/5/6/7/8 were higher in lung adenocarcinoma and squamous cell lung carcinoma tissues than in lung tissues, whereas the expression level of E2F4 was lower in the former than in the latter. The expression levels of E2F2/4/5/7/8 were correlated with advanced tumor stage. Survival analysis using the Kaplan-Meier Plotter database revealed that the high transcription levels of E2F1/2/4/5/7/8 were associated with low relapse-free survival (RFS) in all of the patients with LC. Conversely, high E2F3/6 levels predicted high RFS in these patients. This study implied that E2F3/6/7 are potential targets of precision therapy for patients with LC and that E2F1/2/4/5/8 are new biomarkers for the prognosis of LC.

Lung cancer, the leading cause of cancer deaths worldwide, is characterized with malignant cell growth. Advances in next-generation sequencing has helped us further understand RNA and identify novel circular RNAs (circRNAs) that may be useful in the early diagnosis and treatment of lung cancer. Similar to other noncoding RNAs, circRNAs present diverse biological functions in normal and disease states, including various types of cancers. This review focuses mainly on the poorly understood functions of circRNA in lung cancer. This paper also summarizes the recent advances in circRNA biogenesis, analyzes the role of circRNAs in cancers, and discusses the potential mechanisms of circRNAs in lung cancer.

A novel method for the determination of peroxynitrite using folic acid as a fluorescent probe is described. The method is based on the oxidation of the reduced, low-fluorescent folic acid by peroxynitrite to produce a high-fluorescent emission product. The fluorescence increase is linearly related to the concentration of peroxynitrite in the range of 3x10(-8) to 5.0x10(-6)molL(-1) with a correlation coefficient of 0.998, and the detection limit is 1x10(-8)molL(-1). Interferences from some metal ions normally seen in biological samples, and also some anions structurally similar to peroxynitrite were studied. The optimal conditions for the detection of peroxynitrite were evaluated.

Sulforaphane (SFN) possesses powerful chemo-preventive effects and plays a crucial role on oxidative stress and inflammatory. In our recent study, SFN treatment could relieve muscular dystrophy in mdx mice by activating Nrf2 (NF-E2 related factor 2). Moreover, our findings indicated that SFN-activated Nrf2 alleviated muscle inflammation in dystrophin-deficient mdx mice through suppressing NF-κB signaling pathway. Collectively, SFNinduced Nrf2 molecular pathway might be a promising approach for treatment of the patients with Duchenne muscular dystrophy.

In this work, the reactions of nitrite (NO2-) and peroxynitrite (ONOO-) with organic molecules as well as with hemoglobin (Hb) were examined and the potential interference with the detection of hydrogen peroxide and Hb was investigated. ONOO- at low concentrations (35-140 microM) induced a concentration-dependent oxidation of o-phenylenediamine and guaiacol, and this process can be improved by the addition of Hb in a concentration-dependent manner. This enhancing effect of Hb was possibly due to the formation of such highly reactive species as ferrylHb during the reaction of ONOO- and Hb. NO2- also oxidized the aromatic amine o-phenylenediamine, but its efficiency was much lower than that of ONOO-. A 300-fold excess of NO2- over hydrogen peroxide inhibited the oxidation of Pyrogallol Red mediated by hydrogen peroxide and Hb, which was due in part to the reaction of NO2- with Hb ferryl species compound I and compound II and the phenoxyl radical. These data suggest that ONOO- and NO2- can interfere with the detection of hydrogen peroxide. The overestimation or underestimation of the hydrogen peroxide detected is dependent upon the organic molecule utilized for detection and the relative rate of NO2-, superoxide, and ONOO- generation.

In aqueous neutral sodium dodecyl sulfate (SDS) solution, as meso-tetra(4-hydroxyphenyl)porphyrin (THPP) monomers insert SDS aggregation, a strong porphyrin–porphyrin interaction is observed, and then the porphyrin J-aggregates form slowly. The concentration of SDS necessary to give the maximum amount of J-aggregates is 5.0 mM. The J-aggregates have been studied by optical absorption, fluorescence, and resonance light scattering spectroscopies. The J-aggregates have two strong exciton bands corresponding to the B-band and Q-bands of THPP monomers. The total fluorescence of THPP is quenched due to the aggregate formation. A strong and sharply peaked resonance light scattering signal (at 490 nm) which suggests a delocalized excitonic state is observed just slightly to the red of the J-aggregates absorption maximum. The J-aggregates are still very steady even if the solutions were stored in the dark for more than a year.

Methemoglobin (metHb) was used as a mimetic enzyme for peroxidase to catalyze the oxidation reaction of o-phenylenediamine (OPDA) with H2O2 functioning as an oxidant. A reaction intermediate was obtained in two-phase aqueous-organic system and an absorption peak at 710 nm was confirmed to be that of the intermediate in relation to OPDA. The isolated product and intermediate were characterized by UV-V is and IR spectrophotometry and HPLC-tandem mass spectrometry. The results showed that the product is 2,3-diaminophenazine, the molecular mass of the intermediate is 212 daltons, and a conceivable structure of the intermediate is suggested. Combining the catalyzed reaction mechanism of peroxidase and our experimental results, a conceivable oxidation reaction mechanism of OPDA and H2O2 using metHb as catalyst is proposed.

In the present study, a novel spectrophotometric method for the determination of peroxynitrite using, o‐phenylenediamine as a probe is described. The method is based on the oxidation of o‐phenylenediamine, a colorless substance, by peroxynitrite to give a colored product. The absorbance increase of the reaction system is linearly related to the concentration of peroxynitrite in the range of 4.4 × 10−7–8.0 × 10−6 mol l−1 with a detection limit of 1.7 × 10−7 mol l−1 (3σ). The optimal conditions for the detection of peroxynitrite were evaluated and the possible detection mechanism was also discussed in this paper.

Superoxide anion and NO can react to form the highly oxidizing species peroxynitrite (ONOO − ) which can react directly with hemoglobin (Hb) even in the presence of physiological concentration CO 2 . This research was to determine the ONOO − -mediated oxidation damage to the heme of oxyhemoglobin (oxyHb) under conditions expected in blood. Results showed that 8-10 mol ONOO − was needed to quickly and completely convert 1 mol oxyHb to methemoglobin (metHb). ONOO − (20-140 μM) caused rapid and extensive formation of metHb from oxyHb (50 μM) mainly occurring within first 5-20 min of incubation. The conversion efficiency reached 16%, 48%, 60%, 79% and 88% output of metHb after 90 min of incubation at 0, 20, 40, 100, and 140 μM ONOO − respectively. 1 mM CO 2 caused a small decrease in the ability of ONOO − to oxidize oxyHb, and ONOO − -promoted conversion of oxyHb to metHb increased when pH decreased from 8.0 to 6.0. Relatively lower temperature in blood condition will inhibit this reaction in some degree. We postulate that ONOO − can mediate oxidation damage to the heme, and cause heme loss from the hydrophobic cavity of Hb when its concentration exceeded 90 μM. These results indicated that ONOO − could convert oxyHb to metHb under the conditions expected in blood, and this reaction was regulated by CO 2 concentration, reaction time, temperature and pH value.