Gut Microbiome Was Highly Related to the Regulation of Metabolism in Lung Adenocarcinoma Patients.

Background: Lung adenocarcinoma (LUAD) is one of the most predominant subtypes of lung cancer. The gut microbiome plays a vital role in the pathophysiological processes of various diseases, including cancers. Methods: In the study, 100 individuals were enrolled. In total 75 stool and blood samples were analyzed with 16s-rRNA gene sequencing and metabolomics (30 from healthy individuals (H); 45 from LUAD patients). In addition, 25 stool samples were analyzed with metagenomics (10 from H; 15 from LUAD). The linear discriminant analysis (LDA) effect size (LefSe) and logistic regression analysis were applied to identify biomarkers' taxa and develop a diagnostic model. The diagnostic power of the model was estimated with the receiver operating characteristic curve (ROC) by comparing the area under the ROC (AUC). The correlation between biomarker's taxa and metabolites was calculated using the Spearman analysis. Results: The α and ß diversity demonstrated the composition and structure of the gut microbiome in LUAD patients were different from those in healthy people. The top three abundance of genera were Bacteroides (25.06%), Faecalibacterium (11.00%), and Prevotella (5.94%). The LefSe and logistic regression analysis identified three biomarker taxa (Bacteroides, Pseudomonas, and Ruminococcus gnavus group) and constructed a diagnostic model. The AUCs of the diagnostic model in 16s-rRNA gene sequencing and metagenomics were 0.852 and 0.841, respectively. A total of 102 plasma metabolites were highly related to those three biomarkers' taxa. Seven metabolic pathways were enriched by 102 plasma metabolites, including the Pentose phosphate pathway, Glutathione metabolism. Conclusions: In LUAD patients, the gut microbiome profile has significantly changed. We used three biomarkers taxa to develop a diagnostic model, which was accurate and suitable for the diagnosis of LUAD. Gut microbes, especially those three biomarkers' taxa, may participate in regulating metabolism-related pathways in LUAD patients, such as the pentose phosphate pathway and glutathione metabolism.

DNMT1 promotes cell proliferation via methylating hMLH1 and hMSH2 promoters in EGFR-mutated non-small cell lung cancer.

Aberrant DNA methylation is a common form of epigenetic alterations and it has been proved to be closely related to many cancers, while its role in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) is not clear. This study focuses on the role of DNA methyltransferase 1 (DNMT1) in EGFR-mutated NSCLC pathogenesis. First, the expression of DNMT1 was up-regulated, while the expressions of human mutL homolog 1(hMLH1) and human mutS homolog 2 (hMSH2) were down-regulated in EGFR-mutated NSCLC patients and cell line HCC827. The results of the correlation analysis showed that DNMT1 expression was inversely correlated with the expressions of hMLH1 and hMSH2. Then, we found that DNMT1 enhanced the promoter methylation levels of hMLH1 and hMSH2, thus suppressing their expressions. DNMT1 knockdown inhibited the proliferation of HCC827 cells, while both hMLH1 knockdown and hMSH2 knockdown could eliminate its inhibitory effect on cell proliferation. In xenograft mouse models, lentiviral vector-sh-DNMT1 could significantly reduce tumor volumes, confirmed that DNMT1 inhibited tumor cell proliferation in vivo. In conclusion, DNMT1 suppressed the expressions of hMLH1 and hMSH2 via elevating their promoter methylation, thus promoting cell proliferation in EGFR-mutated NSCLC.

Effects of atmospheric-plasma system on energy efficiency improvement and emissions reduction from a diesel engine.

Efficient energy usage and energy saving is one of the nowadays necessity for all scientists of IC engine. This is because of the current environmental challenges that have tremendously increased concerning air pollution, particularly pollutant emissions from vehicles. Yet, industries and governments alike have disregarded this phenomenon which has been considerably contributing to climate change. It is against this background that, the research works carried out in this present study is predominantly focusing on improving energy efficiency and reducing emission levels from diesel engines. This can be achieved with the help of atmospheric-plasma system which can offer a noble solution to the above-mentioned challenges due to its potential to improve combustion efficiency which leads to energy efficiency, while reducing emission levels from diesel engines. In this study, the performance and emissions of a diesel generator supplemented with an atmospheric-plasma system was examined. The diesel engine was used to examine the effects of fuel composition, or brake specific fuel consumption, thermal efficiency and pollutant emissions at different plasma system voltages. To this end, we equally examined the effects of atmospheric-plasma system on energy efficiency improvement and emissions reduction from diesel engine as the main purpose of this study. We do so by testing the diesel-fueled engine generator under the atmospheric-plasma system. The tests were carried out at a constant state condition with the engine running at 2200 rpm with torque and power outputs of 10.4 Nm (75% of the max load) and 2.1 kW, separately, for the tested fuels and this was used to increase the output voltage of the plasma system during this study. The plasma system ionized the intake air and improved the formation of free radicals upon combustion. During this study, the output voltage of the plasma was set within the range of 0-7 kV. The experimental results have indicated that formaldehyde, acetaldehyde and acrolein account for more than 75% of total carbonyl compounds emissions. Simultaneously, it was also observed from the results that higher plasma system voltage reduces pollutants emissions levels. Hence, such reduction is predominantly evident for nitrogen oxides, particulate matters and carbon monoxide. However, the marginal improvements of engine performance and emissions reduction become insignificant when the plasma system voltage reaches 6 kV. On the other hand, increasing the amount of plasma system voltages in diesel engine continues to significantly reduce pollutant emissions.

Pharmacology and pharmacokinetics of the antiviral agent beta-D-2',3'-dideoxy-3'-oxa-5-fluorocytidine in cells and rhesus monkeys.

Beta-D-2',3'-dideoxy-3'-oxa-5-fluorocytidine (D-FDOC) is an effective inhibitor of human immunodeficiency virus 1 (HIV-1) and HIV-2, simian immunodeficiency virus, and hepatitis B virus (HBV) in vitro. The purpose of this study was to evaluate the intracellular metabolism of d-FDOC in human hepatoma (HepG2), human T-cell lymphoma (CEM), and primary human peripheral blood mononuclear (PBM) cells by using tritiated compound. By 24 h, the levels of D-FDOC-triphosphate (D-FDOC-TP) were 2.8 +/- 0.4, 6.7 +/- 2.3, and 2.0 +/- 0.1 pmol/10(6) cells in HepG2, CEM, and primary human PBM cells, respectively. Intracellular D-FDOC-TP concentrations remained greater than the 50% inhibitory concentration for HIV-1 reverse transcriptase for up to 24 h after removal of the drug from cell cultures. In addition to d-FDOC-monophosphate (D-FDOC-MP), -diphosphate (D-FDOC-DP), and -TP, D-FDOC-DP-ethanolamine and d-FDOC-DP-choline were detected in all cell extracts as major intracellular metabolites. D-FDOC was not a substrate for Escherichia coli thymidine phosphorylase. No toxicity was observed in mice given D-FDOC intraperitoneally for 6 days up to a dose of 100 mg/kg per day. Pharmacokinetic studies in rhesus monkeys indicated that D-FDOC has a t(1/2) of 2.1 h in plasma and an oral bioavailability of 38%. The nucleoside was excreted unchanged primary in the urine, and no metabolites were detected in plasma or urine. These results suggest that further safety and pharmacological studies are warranted to assess the potential of this nucleoside for the treatment of HIV- and HBV-infected individuals.

Antiviral activity and pharmacokinetics of 1-(2,3-dideoxy-2-fluoro-beta-L-glyceropent-2-enofuranosyl)cytosine.

1-(2,3-Dideoxy-2-fluoro-beta-L-glyceropent-2-enofuranosyl)cytosine (L-2'-Fd4C) is an L-nucleoside analogue with both anti-human immunodeficiency virus (HIV) and anti-hepatitis B virus (HBV) activity with median effective concentrations of 0.12 microM in peripheral blood mononuclear cells and 0.002 microM in HepG2-2.2.15 cells, respectively. The purpose of this study was to examine the antihepadnavirus potency and pharmacokinetics of L-2'-Fd4C in vivo. HBV-transgenic mice treated intraperitoneally with L-2'-Fd4C showed a reduction of HBV levels in their blood comparable to that produced by lamivudine. The pharmacokinetics of L-2'-Fd4C in rhesus monkeys was evaluated after intravenous and oral administration. The concentrations in plasma declined in a biexponential manner after intravenous administration, with a long terminal-phase half-life of 5.02 h. The steady-state volumes of distribution and systemic clearance were 1.09 liter x kg(-1) and 0.25 liter x h(-1) x kg(-1), respectively, with a renal clearance of 0.16 liter x h(-1) x kg(-1). The oral bioavailability was approximately 44%. About 53% of the compound administered intravenously and 19% of that administered orally were recovered unchanged in the urine within the 24-h urine collection period, and no other metabolite was detected. The compound penetrated the central nervous system at concentrations that exceeded the median effective antiviral concentration against HIV in cell cultures. Based upon these observations, further testing to develop this agent for treatment of HIV and HBV infections is warranted.