Optimization of pineapple juice amount used as a negative oral contrast agent in magnetic resonance cholangiopancreatography

To evaluate the potential variability of Manganese (Mn2+) in commercial pineapple juice (PJ) produced in different years and to identify the optimal Mn2+ concentration in the correct amount of PJ to be administered prior to Magnetic Resonance Cholangiopancreatography (MRCP) in order to suppress the gastroduodenal (GD) liquid signal. The Mn2+ concentration in PJ produced in different years was defined using Atomic Absorption Spectrometry. The optimal Mn2+ concentration and the amount of PJ, were estimated in an in-vitro analysis, and were then prospectively tested in a population of patients who underwent MRCP. The results were compared with those achieved with the previous standard amount of PJ used in a similar population. The concentrations of Mn2+ in commercial PJ produced in different years did not differ. A total amount of 150 ml (one glass) of PJ having a high Mn2+ content (2.37 mg/dl) was sufficient for the suppression of the GD liquid signal, despite the additional dilution caused by GD liquids since it led to a final concentration of Mn2+ of 0.5–1.00 mg/dl. The optimized single-dose oral administration of 150 ml (approximately one glass) of PJ having a high Mn2+ concentration prior to MRCP was adequate to guarantee the correct amount of Mn2+ to suppress the GD signal.

Molecular insights into the unusually promiscuous and catalytically versatile Fe(II)/α-ketoglutarate-dependent oxygenase SptF

Non-heme iron and α-ketoglutarate-dependent (Fe/αKG) oxygenases catalyze various oxidative biotransformations. Due to their catalytic flexibility and high efficiency, Fe/αKG oxygenases have attracted keen attention for their application as biocatalysts. Here, we report the biochemical and structural characterizations of the unusually promiscuous and catalytically versatile Fe/αKG oxygenase SptF, involved in the biosynthesis of fungal meroterpenoid emervaridones. The in vitro analysis revealed that SptF catalyzes several continuous oxidation reactions, including hydroxylation, desaturation, epoxidation, and skeletal rearrangement. SptF exhibits extremely broad substrate specificity toward various meroterpenoids, and efficiently produced unique cyclopropane-ring-fused 5/3/5/5/6/6 and 5/3/6/6/6 scaffolds from terretonins. Moreover, SptF also hydroxylates steroids, including androsterone, testosterone, and progesterone, with different regiospecificities. Crystallographic and structure-based mutagenesis studies of SptF revealed the molecular basis of the enzyme reactions, and suggested that the malleability of the loop region contributes to the remarkable substrate promiscuity. SptF exhibits great potential as a promising biocatalyst for oxidation reactions.

Impact of circ-0000221 in the Pathogenesis of Hepatocellular via Modulation of miR-661–PTPN11 mRNA Axis

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in Egypt. A deep understanding of the molecular events occurring in HCC can facilitate the development of novel diagnostic and/or therapeutic approaches. In the present study, we describe a novel axis of hsa-circ-0000221–miR-661–PTPN11 mRNA proposed by in silico and in vitro analysis and its role in HCC pathogenesis. We observe a reduction in the expression levels of hsa-circ-0000221 and PTPN11 mRNA in HCC patients’ sera tested compared with control subjects. The reduction occurs with a concomitant increase in the expression of miR-661. Furthermore, the introduction of exogenous hsa-circ-0000221 into Hep-G2 or SNU449 cell lines results in detectable decrease in cellular viability and an increase in apoptotic manifestations that is associated with G1 accumulation and CCDN1 overexpression. Altogether, these findings indicate the tumor-suppressive role of hsa-circ-0000221 in HCC, which acts through miR-661 inhibition, along with a subsequent PTPN11 mRNA increase, where PTPN11 is known to inhibit cell proliferation in many forms of cancer. Our study encourages further investigation of the role of circRNAs in cancer and their potential use as molecular biomarkers.