We produced an LRAT gene knock-out mouse strain and assessed whether LRAT-/- mice were more susceptible to vitamin A deficiency than wild type (WT) mice.
Our observation suggests an involvement of enhanced CYP26A1 expression causing a functional VAD state in skin that can potentially lead to neoplastic transformation of keratinocytes in an early phase during skin carcinogenesis.
Vitamin A deficiency is associated with carcinogenesis, and upregulation of CYP26A1, a major retinoic acid (RA)-catabolizing enzyme, has recently been shown in cancer.
Liver hepcidin and ferritin mRNA levels were upregulated by VAD; however, this condition did not promote any change on the expression of those genes that participate in the iron absorption.
Vitamin A deficiency increased liver hepcidin mRNA and iron spleen concentrations; however, iron deficiency in vitamin A-deficient rats deeply inhibits liver hepcidin mRNA expression and significantly increases divalent metal transporter-1 mRNA levels.
The IRP2 mRNA level of the rats in the test groups was approximately two times that of the control group, whereas the Fn mRNA level and the TfR mRNA level were downregulated and upregulated, respectively, by the vitamin A deficiency.
We report sensitivities of 88%, 100%, and 80% and specificities of 97%, 100%, and 97% for iron deficiency (ferritin <15 ng/mL or 32 pmol/L), vitamin A deficiency (retinol-binding protein <14.7 μg/mL or 0.70 μmol/L) and inflammation status (C-reactive protein >3.0 μg/mL or 120 nmol/L), respectively.
We compared five approaches to adjust RBP for inflammation and estimate VAD prevalence (defined as RBP < 0.7 µmol/L): (1) ignoring inflammation; (2) excluding individuals with inflammation (C-reactive protein (CRP) >5 mg/L or alpha1-acid glycoprotein (AGP) >1 g/)L; (3) multiplying each individual's RBP by an internal correction factor; (4) by an external correction factor; and (5) using regression (corrected RBP = exp(InRBP - β<sub>1</sub> (lnCRP<sub>obs</sub> -lnCRP<sub>ref</sub> ) - β<sub>2</sub> (lnAGP<sub>obs</sub> -lnAGP<sub>ref</sub> )).
There was no added effect of adjusting for malaria on the estimated VAD after adjusting for CRP and AGP.<b>Conclusions:</b> The use of regression correction (derived from internal data), which accounts for the severity of inflammation, to estimate the prevalence of VAD in PSC in regions with inflammation and malaria is supported by the analysis of the BRINDA data.
After excluding children with malaria parasitaemia, inflammation (CRP > 5 mg L(-1) ), iron deficiency (ferritin < 12 μg L(-1) ) or vitamin A deficiency (RBP < 0.7 μg L(-1) ), the prevalence of anaemia among those without α(+) -thalassaemia (43.0%) remained significantly lower than that among children who were either heterozygotes (53.5%) or homozygotes (67.7%, P = 0.03).
Taken together, our findings indicate that SULT1C2A enhanced Foxo4 expression by negatively modulating rno-miR-466c-5p expression via the PI3K-ATK signalling pathway in the rat model of VAD-CS.
Taken together, our findings indicate that SULT1C2A enhanced Foxo4 expression by negatively modulating rno-miR-466c-5p expression via the PI3K-ATK signalling pathway in the rat model of VAD-CS.
Taken together, our findings indicate that SULT1C2A enhanced Foxo4 expression by negatively modulating rno-miR-466c-5p expression via the PI3K-ATK signalling pathway in the rat model of VAD-CS.
Taken together, our findings indicate that SULT1C2A enhanced Foxo4 expression by negatively modulating rno-miR-466c-5p expression via the PI3K-ATK signalling pathway in the rat model of VAD-CS.
Relative to the VAD group, the VAN group also had increased mRNA and protein levels of RARα and PI3K, and upregulated phosphorylated Akt/Bad levels in vivo.