The hair metabolome has been recognized as a valuable source of information in pregnancy research, as it provides stable metabolite information that could assist with studying biomarkers or metabolic mechanisms of pregnancy and its complications. We tested the hypothesis that hair segments could be used to reflect a metabolite profile containing information from both endogenous and exogenous compounds accumulated during the nine months of pregnancy. Segments of hair samples corresponding to the trimesters were collected from 175 pregnant women in New Zealand. The hair samples were analysed using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. In healthy pregnancies, 56 hair metabolites were significantly different between the first and second trimesters, while 62 metabolites were different between the first and third trimesters (p < 0.05). Additionally, three metabolites in the second trimester hair samples were significantly different between healthy controls and women who delivered small-for-gestational-age infants (p < 0.05), and ten metabolites in third trimester hair were significantly different between healthy controls and women with gestational diabetes mellitus (p < 0.01). The findings from this pilot study provide improved insight into the changes of the hair metabolome during pregnancy, as well as highlight the potential of the maternal hair metabolome to differentiate pregnancy complications from healthy pregnancies.
Background: Oral uptake of lycopene has been shown to be beneficial for preventing myocardial ischemia-reperfusion (I/R) injury. However, the strong first-pass metabolism of lycopene influences its bioavailability and impedes its clinic application. In this study, we determined an intravenous (IV) administration dose of lycopene protects against myocardial infarction (MI) in a mouse model, and investigated the effects of acute lycopene administration on reactive oxygen species (ROS) production and related signaling pathways during myocardial I/R. Methods: In this study, we established both in vitro hypoxia/reoxygenation (H/R) cell model and in vivo regional myocardial I/R mouse model by ligating left anterior artery descending. TTC dual staining was used to assess I/R induced MI in the absence and presence of acute lycopene administration via tail vein injection. Results: Lycopene treatment (1 μM) before reoxygenation significantly reduced cardiomyocyte death induced by H/R. Intravenous administration of lycopene to achieve 1 μM concentration in circulating blood significantly suppressed MI, ROS production, and JNK phosphorylation in the cardiac tissue of mice during in vivo regional I/R. Conclusion: Elevating circulating lycopene to 1 μM via IV injection protects against myocardial I/R injury through inhibition of ROS accumulation and consequent inflammation in mice.
Breast cancer is characterized by overexpression of superoxide dismutase (SOD) and downregulation of catalase and more resistance to hydrogen peroxide (H2O2) than normal cells. Thus, relatively high H2O2 promotes breast cancer cell growth and proliferation. However, excessive intracellular H2O2 leads to death of breast cancer cells. In cancer cells, high level ascorbic acid (Asc) is able to be autoxidized and thus provides an electron to oxygen to generate H2O2. In the present study, we demonstrated that triethylenetetramine (TETA) enhances Asc autoxidation and thus elevates H2O2 production in MCF-7 cells. Furthermore, Asc/TETA combination significantly impaired cancer cell viability, while having much milder effects on normal cells, indicating Asc/TETA could be a promising therapy for breast cancer. Moreover, SOD1 and N-acetyl-L-cysteine failed to improve MCF-7 cells viability in the presence of Asc/TETA, while catalase significantly inhibited the cytotoxicity of Asc/TETA to breast cancer cells, strongly suggesting that the selective cytotoxicity of Asc/TETA to cancer cells is H2O2-dependent. In addition, Asc/TETA induces RAS/ERK downregulation in breast cancer cells. Animal studies confirmed that Asc/TETA effectively suppressed tumor growth in vivo. In conclusion, TETA synergizes pharmacologic Asc autoxidation and H2O2 overproduction in breast cancer cells, which suppresses RAS/ERK pathway and results in apoptosis.
The fetus undergoes a crucial period of neurodevelopment in utero. The maternal hair metabolome provides an integrated record of the metabolic state of the mother prior to, and during pregnancy. We investigated whether variation in the maternal hair metabolome was associated with neurodevelopmental differences across infants. Maternal hair samples and infant neurocognitive assessments (using the Bayley III Scales of Infant Development at 24 months) were obtained for 373 infant-mother dyads between 26–28 weeks’ gestation from the Growing Up in Singapore Towards Healthy Outcomes cohort. The hair metabolome was analysed using gas chromatography-mass spectrometry. Intensity measurements were obtained for 276 compounds. After controlling for maternal education, ethnicity, and infant sex, associations between metabolites and expressive language skills were detected, but not for receptive language, cognitive or motor skills. The results confirm previous research associating higher levels of phthalates with lower language ability. In addition, scores were positively associated with a cluster of compounds, including adipic acid and medium-chain fatty acids. The data support associations between the maternal hair metabolome and neurodevelopmental processes of the fetus. The association between phthalates and lower language ability highlights a modifiable risk factor that warrants further investigation.
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