5 research outputs found
Development and Application of an LC-MS/MS Untargeted Exposomics Method with a Separated Pooled Quality Control Strategy
Pooled quality controls (QCs) are usually implemented within untargeted methods to improve the quality of datasets by removing features either not detected or not reproducible. However, this approach can be limiting in exposomics studies conducted on groups of exposed and nonexposed subjects, as compounds present at low levels only in exposed subjects can be diluted and thus not detected in the pooled QC. The aim of this work is to develop and apply an untargeted workflow for human biomonitoring in urine samples, implementing a novel separated approach for preparing pooled quality controls. An LC-MS/MS workflow was developed and applied to a case study of smoking and non-smoking subjects. Three different pooled quality controls were prepared: mixing an aliquot from every sample (QC-T), only from non-smokers (QC-NS), and only from smokers (QC-S). The feature tables were filtered using QC-T (T-feature list), QC-S, and QC-NS, separately. The last two feature lists were merged (SNS-feature list). A higher number of features was obtained with the SNS-feature list than the T-feature list, resulting in identification of a higher number of biologically significant compounds. The separated pooled QC strategy implemented can improve the nontargeted human biomonitoring for groups of exposed and nonexposed subjects
Functionalization of kaolinite for removal of phosphate from urban sewage
The PO43− widespread in urban sewages promotes eutrophication of water sources, with harmful effects to natural life and endanger human health. The removal of PO43− from urban sewage requires treatment at tertiary level, with high costs and low efficiency in most cases. Thus, a functionalization method for surface modification of kaolinite was proposed to improve the removal of PO43− from urban sewage. The kaolinite commercial did not remove PO43- from aqueous solution. However, the functionalized kaolinite (FK) was efficient, with a maximum removal capacity of 8.4 ± 0.1 mg PO43−/L, within less than 1 min of reaction. The removal of PO43- is associated with precipitation of pyromorphite, a mineral with low solubility (Ksp < 10−79,6). Finally, real urban sewage samples (raw and treated) were also tested for removal of PO43- using FK, confirming its effectiveness. The central aspects of this development are: • Functionalized kaolinite (FK), with Pb(II), for removal of PO43− from urban sewage was studied. • The FK was efficient for removal of up to 8.4 mg PO43−/L from aqueous solution, within a short reaction time. • The precipitation of pyromorphite was the mechanism responsible for removal of PO43- and FK efficiency have been confirmed for real urban sewage samples
Global DNA hypomethylation in peripheral blood mononuclear cells as a biomarker of cancer risk
Background:Global DNA hypomethylation is an early molecular event in carcinogenesis. Whether methylation measured in peripheral blood mononuclear cells(PBMCs) DNA is a clinically reliable biomarker for early detection or cancer risk assessment is to be established. Methods:From an original sample-set of 753 male and female adults(aged 64.8\ub17.3years),PBMCs DNA methylation was measured in 68 subjects with history of cancer at time of enrollment and 62 who developed cancer during follow-up. Age-and sex-matched controls for prevalent and incident cancer cases(n=68 and n=58,respectively)were also selected. Global DNA methylation was assessed by LC/MS. Methylenetetrahydrofolate reductase(MTHFR) 677C>T genotype and plasma folate concentrations were also determined for the known gene-nutrient interaction affecting DNA methylation. Results:Cancer subjects had significantly lower PBMCs-DNA methylation than controls [4.39(95%CIs 4.25-4.53) vs. 5.13(95%CIs 5.03-5.21)%mCyt/(mCyt+Cyt),PT genotype and folate interact for determining DNA methylation,so that MTHFR677TT carriers with low folate had the lowest DNA methylation and
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concordantly showed a higher prevalence of cancer history (OR=7.04,95%CIs 1.52- 32.63,P=0.013). Conclusions:Genomic PBMCs-DNA methylation may be a useful epigenetic biomarker for early detection and cancer risk estimation.
Impact:This study identifies a threshold for PBMCs-DNA methylation to detect cancer- affected from cancer\u2013free subjects and an at-risk condition for cancer based on genomic DNA methylation and MTHFR677C>T-folate status
Global DNA hypomethylation in peripheral blood mononuclear cells as a biomarker of cancer risk
DNA methylation is a reversible epigenetic phenomenon that can be modified by nutrients such as folate and influenced by the MTHFR677C>T polymorphism in a gene-nutrient interaction manner. In human cancer, global DNA hypomethylation is an almost universal finding.Cancer subjects had lower plasma folate concentrations (P=0.003), higher frequency of MTHFR677TT (P=0.013) and lower PBMCs-DNA methylation than controls (P<0.0001). A DNA methylation threshold of 4.74% categorized cancer patients from controls. Subjects with cancer at follow-up had at enrollment lower DNA methylation than controls (P<0.0001).
The association of MTHFR677TT and low plasma folate showed the lowest DNA methylation levels (4.39%). Cancer deaths had a lower DNA methylation compared with other cause deaths (P=0.015) and the survivors had an increased DNA methylation compared to cancer (P=0.004).
Low global DNA methylation in PBMCs may be a useful predictive biomarker of cancer
Global DNA Hypomethylation in Peripheral Blood Mononuclear Cells as a Biomarker of Cancer Risk
BACKGROUND: Global DNA hypomethylation is an early molecular event in carcinogenesis. Whether methylation measured in peripheral blood mononuclear cells(PBMCs) DNA is a clinically reliable biomarker for early detection or cancer risk assessment is to be established. METHODS: From an original sample-set of 753 male and female adults(aged 64.8±7.3years),PBMCs DNA methylation was measured in 68 subjects with history of cancer at time of enrollment and 62 who developed cancer during follow-up. Age-and sex-matched controls for prevalent and incident cancer cases(n=68 and n=58,respectively)were also selected. Global DNA methylation was assessed by LC/MS. Methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype and plasma folate concentrations were also determined for the known gene-nutrient interaction affecting DNA methylation. RESULTS: Cancer subjects had significantly lower PBMCs-DNA methylation than controls [4.39(95%CIs 4.25–4.53) vs. 5.13(95%CIs 5.03–5.21)%mCyt/(mCyt+Cyt), P<0.0001]. A DNA methylation threshold of 4.74% clearly categorized cancer patients from controls so that those with DNA methylation <4.74% showed an increased prevalence of cancer than those with higher levels (91.5% vs. 19%;P <0.001). Subjects with cancer at follow-up had, already at enrollment, reduced DNA methylation compared to controls [4.34(95%CIs 4.24–4.51) vs. 5.08(95%CIs 5.05–5.22)%mCyt/(mCyt+Cyt),P<0.0001].Moreover, MTHFR677C>T genotype and folate interact for determining DNA methylation, so that MTHFR677TT carriers with low folate had the lowest DNA methylation and concordantly showed a higher prevalence of cancer history (OR=7.04,95%CIs 1.52–32.63, P=0.013). CONCLUSIONS: Genomic PBMCs-DNA methylation may be a useful epigenetic biomarker for early detection and cancer risk estimation. IMPACT: This study identifies a threshold for PBMCs-DNA methylation to detect cancer-affected from cancer–free subjects and an at-risk condition for cancer based on genomic DNA methylation and MTHFR677C>T-folate status