Iron deposition in autopsied liver on patients receiving long-term TPN

Background Vitamins and minerals are routinely administered by total parenteral nutrition (TPN). However, in Japan, adjustments in iron dosage are difficult because blended mineral preparations are often used. It is therefore unclear whether the iron content is appropriate in cases of long-term TPN. The aim of the study was to assess the influence of iron administration by long-term TPN on iron deposition in post-mortem liver samples isolated from older deceased patients. Methods Liver tissues were collected from post-mortem autopsies of 187 patients over a period of 15 years. Samples were stained with Prussian blue and histologically evaluated from Grade 0–V by at least three different observers. Specimens with positive and negative iron staining were compared, and positive samples were grouped according to the level and distribution of the staining. Post-mortem blood obtained from the subclavian vein during autopsy was also analysed. Samples were collected for the measurement of unsaturated serum iron, serum iron, albumin, prealbumin, hepcidin, and IL-6 concentrations. Results Iron accumulation in the liver was significantly higher in male patients (p = 0.005) with a history of surgery (p = 0.044) or central vein administration of iron (p<0.001). Additionally, the duration of TPN in the iron-positive group was significantly longer than in the iron-negative group (p = 0.038). Serum analysis revealed that unsaturated serum iron was significantly higher in the iron-negative group and that ferritin and serum iron were significantly higher in the iron-positive group. No other statistically significant differences were observed between the two groups. Conclusions Chronic intravenous administration of iron was associated with iron deposition in the liver, even when given the minimum recommended dosage. In long-term TPN patients, the iron dose should therefore be carefully considered

A non-carboxylating pentose bisphosphate pathway in halophilic archaea

Bacteria and Eucarya utilize the non-oxidative pentose phosphate pathway to direct the ribose moieties of nucleosides to central carbon metabolism. Many archaea do not possess this pathway, and instead, Thermococcales utilize a pentose bisphosphate pathway involving ribose-1, 5-bisphosphate (R15P) isomerase and ribulose-1, 5-bisphosphate (RuBP) carboxylase/oxygenase (Rubisco). Intriguingly, multiple genomes from halophilic archaea seem only to harbor R15P isomerase, and do not harbor Rubisco. In this study, we identify a previously unrecognized nucleoside degradation pathway in halophilic archaea, composed of guanosine phosphorylase, ATP-dependent ribose-1-phosphate kinase, R15P isomerase, RuBP phosphatase, ribulose-1-phosphate aldolase, and glycolaldehyde reductase. The pathway converts the ribose moiety of guanosine to dihydroxyacetone phosphate and ethylene glycol. Although the metabolic route from guanosine to RuBP via R15P is similar to that of the pentose bisphosphate pathway in Thermococcales, the downstream route does not utilize Rubisco and is unique to halophilic archaea

Unveiling Molecular Recognition of Sialoglycans by Human Siglec-10

29 p.-6 fig.-2 tab.-7 fig. supl.-2 tab. supl.-1 graph. abst.Siglec-10 is an inhibitory I-type lectin selectively recognizing sialoglycans exposed on cell surfaces, involved in several patho-physiological processes. The key role Siglec-10 plays in the regulation of immune cell functions has made it a potential target for the development of immunotherapeutics against a broad range of diseases. However, the crystal structure of the protein has not been resolved for the time being and the atomic description of Siglec-10 interactions with complex glycans has not been previously unraveled. We present here the first insights of the molecular mechanisms regulating the interaction between Siglec-10 and naturally occurring sialoglycans. We used combined spectroscopic, computational and biophysical approaches to dissect glycans' epitope mapping and conformation upon binding in order to afford a description of the 3D complexes. Our outcomes provide a structural perspective for the rational design and development of high-affinity ligands to control the receptor functionality.This study was supported by the project ‘‘GLYTUNES’’ funded by MIUR Progetti di Ricerca di Rilevante Interesse Nazionale (PRIN 2017) (2017XZ2ZBK, 2019–2022) to A.S.; by progetto POR SATIN and Progetto POR CampaniaOncoterapia to A.M.; by the European Commission (H2020-MSCA- 814102-SWEET CROSSTALK project) to A.M., R.M., and A.S.. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program under grant agreement No 851356 to R.M. FSE,PON Ricerca e Innovazione 2014–2020, Azione I.1 ‘‘Dottorati Innovativi con caratterizzazione Industriale’’ is acknowledged for funding the PhD grant to R.E.F. Grants by the Spanish Ministry of Science MICINN (CTQ2017-88353-R and fellowship BES 2015–071588 to J.G.-C.) and Wellcome Trust 103744/Z/14/Z to P.R.C. are acknowledged.Peer reviewe