Metabolomics workflow for lung cancer: Discovery of biomarkers.

Lung cancer is one of the most common cancers in the world. Due to the limitations of current diagnostic techniques and methods, most lung cancers are diagnosed at the advanced stage, which is not conducive to early treatment. The rise of metabolomics has provided new ideas for the early diagnosis of lung cancer. As a method for the comprehensive analysis of endogenous metabolites of the biological system, metabolomics has shown significant application potential for the early diagnosis and individualized treatment of various cancers including lung cancers. Via advanced analytical techniques and bioinformatics tools, the metabolome was excavated to find biomarkers related to cancer and its prognosis. In this review, the research methods and workflow of metabolomics are summarized, with an emphasis on the recent discovery of biomarkers and major metabolic pathways for lung cancers.

Application of Ultrasound-Targeted Microbubble Destruction-Mediated Exogenous Gene Transfer in Treating Various Renal Diseases.

Chronic renal disease or acute renal injury could result in end-stage renal disease or renal failure. Sonoporation, induced by ultrasound-targeted microbubble destruction (UTMD), has evolved as a new technology for gene delivery. It increases the transfection efficiency of the genes into target kidney tissues. Moreover, UTMD-mediated gene delivery can directly repair the damaged tissues or improve the recruitment and homing of stem cells in the recovery of injured tissues, which has the potential to act as a non-viral and effective method to current gene therapy. This article reviews the mechanisms and applications of UTMD in terms of renal disease, including diabetic nephropathy, renal carcinoma, acute kidney injury, renal interstitial fibrosis, nephrotoxic nephritis, urinary stones, and acute rejection.

Impact of ambient PM2.5 on adverse birth outcome and potential molecular mechanism.

PM2.5 (particulate matter ≤2.5 µm in aerodynamic diameter) refers to atmospheric particulate matter (PM) with an aerodynamic diameter of equal and less than 2.5 µm that tends to be suspended for long periods of time and travel over long distances in both outdoor and indoor atmospheres. PM2.5, along with the toxic compounds attached on it, may cause a wide range of disorders. The fetus is considered to be highly susceptible to a variety of toxicants including atmospheric pollutants such as PM2.5 through prenatal exposure. To better understand the relationship between maternal exposure to PM2.5 and adverse birth outcomes for reproduction and fetus development, we studied the published data on this issue including case-control studies, cohort studies and meta-analyses studies, and summarized the basic impact of ambient particulate matter on adverse birth outcomes. Research evidence indicates that PM2.5 has a potential to induce low birth weight (LBW), preterm birth (PTB), and stillbirth. A further in-depth analysis shows that oxidative stress, DNA methylation, mitochondrial DNA (mtDNA) content alteration, and endocrine disruptions may all play an important role in PM2.5 induced adverse effects to pregnant women and fetuses. In addition, PM2.5 exposure can cause male reproductive toxicity, leading to associated adverse pregnancy outcomes.

In vitro evaluation of the toxicity and underlying molecular mechanisms of Janus Fe3 O4 -TiO2 nanoparticles in human liver cells.

Recent studies show that Janus Fe3 O4 -TiO2 nanoparticles (NPs) have potential applications as a multifunctional agent of magnetic resonance imaging (MRI) and photodynamic therapy (PDT) for the diagnosis and therapy of cancer. However, little work has been done on their biological effects. To evaluate the toxicity and underlying molecular mechanisms of Janus Fe3 O4 -TiO2 nanoparticles, an in vitro study using a human liver cell line HL-7702 cells was conducted. For comparison, the Janus Fe3 O4 -TiO2 NPs parent material TiO2 NPs was also evaluated. Results showed that both Fe3 O4 -TiO2 NPs and TiO2 NPs decreased cell viability and ATP levels when applied in treatment, but increased malonaldehyde (MDA) and reactive oxygen species (ROS) generation. Mitochondria JC-1 staining assay showed that mitochondrial membrane permeability injury occurred in both NPs treated cells. Cell viability analysis showed that TiO2 NPs induced slightly higher cytotoxicity than Fe3 O4 -TiO2 NPs in HL7702 cells. Western blotting indicated that both TiO2 NPs and Fe3 O4 -TiO2 NPs could induce apoptosis, inflammation, and carcinogenesis related signal protein alterations. Comparatively, Fe3 O4 -TiO2 NPs induced higher signal protein expressions than TiO2 NPs under a high treatment dose. However, under a low dose (6.25 µg/cm2 ), neither NPs had any significant toxicity on HL7702 cells. In addition, our results suggest both Fe3 O4 -TiO2 NPs and TiO2 NPs could induce oxidative stress and have a potential carcinogenetic effect in vitro. Further studies are needed to elaborate the detailed mechanisms of toxicity induced by a high dose of Fe3 O4 -TiO2 NPs.

Hyperphosphorylation of microfilament-associated proteins is involved in microcystin-LR-induced toxicity in HL7702 cells.

Microcystin-LR (MC-LR) has been regarded as a hepatotoxin, which can cause cytoskeletal reorganization, especially of the actin filaments. However, the underlying mechanisms remain unclear. In this study, whether MC-LR could induce microfilaments disruption was verified in the normal human liver cell line HL7702; and then the transcription, translation, and phosphorylation levels of major microfilament-associated proteins were measured; finally, the underlying mechanisms was investigated. After treatment with MC-LR, the actin filaments lost their characteristic filamentous organization in the cells, demonstrating increased actin depolymerization. The mRNA and protein levels of ezrin, vasodilator-stimulated phosphoprotein (VASP), actin-related protein2/3, and cofilin remained unchanged. However, the phosphorylation levels of ezrin and VASP were increased, when treated with 10 µM MC-LR. Moreover, P38 and ERK1/2 were involved in MC-LR-induced hyperphosphorylation of microfilament-associated proteins. In summary, this study demonstrates that MC-LR can cause disruption of actin filaments in HL7702 cells due to MC-LR-induced mitogen-activated protein kinase pathway activation and hyperphosphorylation of different types of microfilament-associated proteins.

Association between polymorphisms in the renin-angiotensin-aldosterone system genes and essential hypertension in the Han Chinese population.

BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) is the most important endocrine blood pressure control mechanism in our body, genes encoding components of this system have been strong candidates for the investigation of the genetic basis of hypertension. However, previous studies mainly focused on limited polymorphisms, thus we carried out a case-control study in the Han Chinese population to systemically investigate the association between polymorphisms in the RAAS genes and essential hypertension. METHODS: 905 essential hypertensive cases and 905 normotensive controls were recruited based on stringent inclusion and exclusion criteria. All 41 tagSNPs within RAAS genes were retrieved from HapMap, and the genotyping was performed using the GenomeLab SNPstream Genotyping System. Logistic regression analysis, Multifactor dimensionality reduction (MDR), stratified analysis and crossover analysis were used to identify and characterize interactions among the SNPs and the non-genetic factors. RESULTS: Serum levels of total cholesterol (TC) and triglyceride (TG), and body mass index (BMI) were significantly higher in the hypertensive group than in the control group. Of 41 SNPs genotyped, rs3789678 and rs2493132 within AGT, rs4305 within ACE, rs275645 within AGTR1, rs3802230 and rs10086846 within CYP11B2 were shown to associate with hypertension. The MDR analysis demonstrated that the interaction between BMI and rs4305 increased the susceptibility to hypertension. Crossover analysis and stratified analysis further indicated that BMI has a major effect, and rs4305 has a minor effect. CONCLUSION: These novel findings indicated that together with non-genetic factors, these genetic variants in the RAAS may play an important role in determining an individual's susceptibility to hypertension in the Han Chinese.

Acute toxicity of intravenously administered titanium dioxide nanoparticles in mice.

BACKGROUND: With a wide range of applications, titanium dioxide (TiO2) nanoparticles (NPs) are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO2 nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. METHODS: In this study, mice were injected intravenously with a single dose of TiO2 NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg). Animal mortality, blood biochemistry, hematology, genotoxicity and histopathology were investigated 14 days after treatment. RESULTS: Death of mice in the highest dose (1387 mg/kg) group was observed at day two after TiO2 NPs injection. At day 7, acute toxicity symptoms, such as decreased physical activity and decreased intake of food and water, were observed in the highest dose group. Hematological analysis and the micronucleus test showed no significant acute hematological or genetic toxicity except an increase in the white blood cell (WBC) count among mice 645 mg/kg dose group. However, the spleen of the mice showed significantly higher tissue weight/body weight (BW) coefficients, and lower liver and kidney coefficients in the TiO2 NPs treated mice compared to control. The biochemical parameters and histological tissue sections indicated that TiO2 NPs treatment could induce different degrees of damage in the brain, lung, spleen, liver and kidneys. However, no pathological effects were observed in the heart in TiO2 NPs treated mice. CONCLUSIONS: Intravenous injection of TiO2 NPs at high doses in mice could cause acute toxicity effects in the brain, lung, spleen, liver, and kidney. No significant hematological or genetic toxicity was observed.