11 research outputs found
Occurrence and Partitioning of Bisphenol Analogues in Adults’ Blood from China
Widespread human exposure and associated
adverse health effects
led to regulations on the usage of bisphenol A (BPA). Several bisphenol
analogues (BPs) have been introduced as BPA alternatives in various
applications. However, these BPs have been shown to exhibit similar
or even stronger endocrine-disrupting activities compared with that
of BPA. Currently, information on the human exposure to BPA alternatives
remains limited. In this study, nine BPs were quantified in 81 pairs
of plasma and red blood cell (RBC) samples from Chinese participants.
In human plasma, the predominant BPs was BPA, bisphenol S (BPS), and
bisphenol AF (BPAF), with the mean concentrations of 0.40, 0.15, and
0.073 ng/mL, respectively. BPA (accounting for 63% of total BPs) and
BPS (18%) were the major BPs in the RBC fraction. Mass fractions in
plasma (<i>F</i><sub>p</sub>) were found to be highest for
BPS (mean, 0.78), followed by BPAF (0.71) and BPA (0.67), indicating
strong partitioning to the plasma fraction. However, bisphenol AP
was more frequently detected in the RBC fraction. Estimated total
daily intake (EDI) of BPA was in the range of 0.0048–0.75 μg/kg
bw/day for the participants, and adults aged >50 years had comparatively
lower EDI. To our knowledge, this is the first study to assess the
occurrence and partitioning of BPA alternatives in paired human plasma
and RBCs from the Chinese general population
PLS-DA score plot and validation plot for lysate samples.
<p>(A) PLS-DA score plot of vehicle-treated CHO-wt and CHO-AβPP<sub>695</sub> lysate samples (R<sup>2</sup>X = 0.474; R<sup>2</sup>Y = 0.985; Q<sup>2</sup> (cum) = 0.808; LV = 2); (B) Validation plot of the PLS-DA model obtained from 100 permutation tests for vehicle-treated lysate samples; (C) PLS-DA score plot of DHA-treated CHO-wt and CHO-AβPP<sub>695</sub> lysate samples (R<sup>2</sup>X = 0.645; R<sup>2</sup>Y = 0.993; Q<sup>2</sup> (cum) = 0.971; LV = 2); (D) Validation plot of the PLS-DA model obtained from 100 permutation tests for DHA-treated lysate samples.</p
DHA treatment increases pyruvate dehydrogenase enzyme concentration in CHO-wt and CHO-AβPP<sub>695</sub> cells.
<p>Pyruvate dehydrogenase activity in CHO-wt and CHO-AβPP<sub>695</sub> cells treated with vehicle or 25 µM DHA. Values are means ± SEM from three independent experiments. **<i>p</i><0.01 and ***<i>p</i><0.001 as compared to CHO-AβPP<sub>695</sub> vehicle treated. Analysis was done via ANOVA with Bonferroni’s post-hoc analysis.</p
Model validation for CHO-wt and CHO-AβPP<sub>695</sub> cells and effect of DHA on Aβ<sub>40</sub> release.
<p>(A) Conditioned medium was collected from CHO-wt and CHO-AβPP<sub>695</sub> cells with and without DHA treatment and subjected to ELISA immunoassays for Aβ<sub>40.</sub> There was negligible release of Aβ<sub>40</sub> from CHO-wt cells as compared to CHO-AβPP<sub>695</sub> cells at 24 and 48 h. A significant decrease was observed in the release of Aβ<sub>40</sub> in CHO-AβPP<sub>695</sub> cells after treatment with 25 µM DHA for 24 h and 48 h. <sup>#</sup><i>p</i><0.001 as compared to CHO-wt vehicle treated cells, <sup>φ</sup><i>p</i><0.05 compared to CHO-AβPP<sub>695</sub> 24 h vehicle treatment and <sup>§</sup><i>p</i><0.001 as compared to CHO-AβPP<sub>695</sub> 48 h vehicle treatment. Analysis was done via ANOVA with Bonferroni’s post-hoc analysis. (B) Western blot analysis of the cell lysates confirm AβPP<sub>695</sub> plasmid overexpression in CHO-AβPP<sub>695</sub> cells compared to CHO-wt.</p
Discriminatory marker metabolites identified from medium and lysate samples of DHA-treated and vehicle-treated CHO-wt and CHO-AβPP<sub>695</sub> cells.
a<p>Metabolite identification using standard compound.</p>b<p>Metabolite identification using NIST library search.</p>c<p>Normalized peak area values expressed as mean ± S.E.M.</p>d<p>Fold change (Δ): CHO-AβPP<sub>695 (treatment)/</sub>CHO-wt <sub>(treatment)</sub>.</p><p>*<i>p</i><0.05 and <sup>ns</sup> not significant when calculated using the independent <i>t</i>-test with Welch’s correction for normalized peak area of CHO-AβPP<sub>695</sub> cells compared to CHO-wt cells for respective treatment groups.</p><p>Abbreviations: DHA – docosahexaenoic acid, TCA – tricarboxylic acid.</p
Metabolites, their associated metabolic pathways and biological relevance in AD.
a<p>Metabolites are grouped together on the basis of their biological relevance. (↑) elevated in AD and (↓) reduced in AD.</p>b<p>Related to metabolites using KEGG database.</p><p>Abbreviations: DHA – docosahexaenoic acid, TCA – tricarboxylic acid.</p
Overlay of GC/TOFMS chromatograms.
<p>(A) Representative GC/TOFMS chromatogram of DHA-treated and vehicle-treated CHO-AβPP<sub>695</sub> cells – lysate (L) and medium (M) samples (B) Representative chromatogram demonstrating discriminatory metabolites between vehicle-treated and DHA-treated CHO-wt cells and CHO-AβPP<sub>695</sub> cells.</p
PLS-DA score plot and validation plot for medium samples.
<p>(A) PLS-DA score plot of vehicle-treated CHO-wt and CHO-AβPP<sub>695</sub> medium samples (R<sup>2</sup>X = 0.679; R<sup>2</sup>Y = 0.994; Q<sup>2</sup> (cum) = 0.929; LV = 3); (B) Validation plot of the PLS-DA model obtained from 100 permutation tests for vehicle-treated medium samples; (C) PLS-DA score plot of DHA-treated CHO-wt and CHO-AβPP<sub>695</sub> medium samples (R<sup>2</sup>X = 0.745; R<sup>2</sup>Y = 0.992; Q<sup>2</sup> (cum) = 0.885; LV = 3); (D) Validation plot of the PLS-DA model obtained from 100 permutation tests for DHA-treated medium samples.</p
Metabonomic Profiling of Bladder Cancer
Early diagnosis and life-long surveillance
are clinically important
to improve the long-term survival of bladder cancer patients. Currently,
a noninvasive biomarker that is as sensitive and specific as cystoscopy
in detecting bladder tumors is lacking. Metabonomics is a complementary
approach for identifying perturbed metabolic pathways in bladder cancer.
Significant progress has been made using modern metabonomic techniques
to characterize and distinguish bladder cancer patients from control
subjects, identify marker metabolites, and shed insights on the disease
biology and potential therapeutic targets. With its rapid development,
metabonomics has the potential to impact the clinical management of
bladder cancer patients in the future by revolutionizing the diagnosis
and life-long surveillance strategies and stratifying patients for
diagnostic, surgical, and therapeutic clinical trials. An introduction
to metabonomics, typical metabonomic workflow, and critical evaluation
of metabonomic investigations in identifying biomarkers for the diagnosis
of bladder cancer are presented
Urinary Metabotyping of Bladder Cancer Using Two-Dimensional Gas Chromatography Time-of-Flight Mass Spectrometry
Cystoscopy
is the gold standard clinical diagnosis of human bladder
cancer (BC). As cystoscopy is expensive and invasive, it compromises
patients’ compliance toward surveillance screening and challenges
the detection of recurrent BC. Therefore, the development of a noninvasive
method for the diagnosis and surveillance of BC and the elucidation
of BC progression become pertinent. In this study, urine samples from
38 BC patients and 61 non-BC controls were subjected to urinary metabotyping
using two-dimensional gas chromatography time-of-flight mass spectrometry
(GC×GC–TOFMS). Subsequent to data preprocessing and chemometric
analysis, the orthogonal partial least-squares discriminant analysis
(OPLS-DA, R<sup>2</sup>X = 0.278, R<sup>2</sup>Y = 0.904 and Q<sup>2</sup>Y (cumulative) = 0.398) model was validated using permutation
tests and receiver operating characteristic (ROC) analysis. Marker
metabolites were further screened from the OPLS-DA model using statistical
tests. GC×GC–TOFMS urinary metabotyping demonstrated 100%
specificity and 71% sensitivity in detecting BC, while 100% specificity
and 46% sensitivity were observed via cytology. In addition, the model
revealed 46 metabolites that characterize human BC. Among the perturbed
metabolic pathways, our clinical finding on the alteration of the
tryptophan-quinolinic metabolic axis in BC suggested the potential
roles of kynurenine in the malignancy and therapy of BC. In conclusion,
global urinary metabotyping holds potential for the noninvasive diagnosis
and surveillance of BC in clinics. In addition, perturbed metabolic
pathways gleaned from urinary metabotyping shed new and established
insights on the biology of human BC