New graft copolymers of hyaluronic acid and polylactic acid: Synthesis and characterization

New graft copolymers have been synthesized, using hyaluronic acid (HA) as a hydrophilic backbone and polylactic acid (PLA) as an aliphatic polyester in order to obtain new polymeric derivatives of HA able to hydrophobically associate in an aqueous medium. Hyaluronic acid with low molecular weight was made soluble in organic solvent by transformation to its tetrabutylammonium (TBA) salt. Using the HA-TBA derivative, the reaction was performed in dimethylsulfoxide adding as a reagent the N-hydroxysuccinimide derivative of PLA. Two HA-PLA graft copolymers have been synthesized and characterized by FT-IR, H-1 NMR spectroscopy and gel permeation chromatography. The interaction between these samples and an aqueous medium has been evaluated by rheological measurements. The obtained data evidenced that both HA-PLA graft copolymers show in aqueous medium a clear tendency for hydrophobic interaction dependent on the amount of PLA chains linked to the HA backbone. (c) 2006 Elsevier Ltd. All rights reserved

Metabolic and mitochondria alterations induced by SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10

Antiviral signaling, immune response and cell metabolism are dysregulated by SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 accessory proteins ORF3a, ORF9b, ORF9c and ORF10 induce a significant mitochondrial and metabolic reprogramming in A549 lung epithelial cells. While ORF9b, ORF9c and ORF10 induced largely overlapping transcriptomes, ORF3a induced a distinct transcriptome, including the downregulation of numerous genes with critical roles in mitochondrial function and morphology. On the other hand, all four ORFs altered mitochondrial dynamics and function, but only ORF3a and ORF9c induced a marked alteration in mitochondrial cristae structure. Genome-Scale Metabolic Models identified both metabolic flux reprogramming features both shared across all accessory proteins and specific for each accessory protein. Notably, a downregulated amino acid metabolism was observed in ORF9b, ORF9c and ORF10, while an upregulated lipid metabolism was distinctly induced by ORF3a. These findings reveal metabolic dependencies and vulnerabilities prompted by SARS-CoV-2 accessory proteins that may be exploited to identify new targets for intervention

Obstetric Outcomes in Women on Lithium: A Systematic Review and Meta-Analysis

Background/Objectives: Lithium taken during pregnancy was linked in the past with increased risk for foetal/newborn malformations, but clinicians believe that it is worse for newborn children not to treat the mothers' underlying psychiatric illness. We set to review the available evidence of adverse foetal outcomes in women who received lithium treatment for some time during their pregnancy. Methods: We searched four databases and a register to seek papers reporting neonatal outcomes of women who took lithium during their pregnancy by using the appropriate terms. We adopted the PRISMA statement and used Delphi rounds among all the authors to assess eligibility and the Cochrane Risk-of-Bias tool to evaluate the RoB of the included studies. Results: We found 28 eligible studies, 10 of which met the criteria for inclusion in the meta-analysis. The studies regarded 1402 newborn babies and 2595 women exposed to lithium. Overall, the systematic review found slightly increased adverse pregnancy outcomes for women taking lithium for both the first trimester only and any time during pregnancy, while the meta-analysis found increased odds for cardiac or other malformations, preterm birth, and a large size for gestational age with lithium at any time during pregnancy. Conclusions: Women with BD planning a pregnancy should consider discontinuing lithium when euthymic; lithium use during the first trimester and at any time during pregnancy increases the odds for some adverse pregnancy outcomes. Once the pregnancy has started, there is no reason for discontinuing lithium; close foetal monitoring and regular blood lithium levels may obviate some disadvantages of lithium administration during pregnancy

Inulin as a multifaceted (active)substance and its chemical functionalization: From plant extraction to applications in pharmacy, cosmetics and food

This review is aimed at critically discussing a collection of research papers on Inulin (INU)in different scientific fields. The first part of this work gives an overview on the main characteristics of native INU, including production, applications in food or cosmetics industries, its benefits on human health as well as its main nutraceutical properties. A particular focus is dedicated to the extraction techniques and to the specific effects of INU on intestinal microbiota. Other than in food industry, the number of INU applications increases dramatically in the pharmaceutical field especially due to its simple chemical functionalization. Thus, aim of this review is also to give practical examples of chemical functionalization performed on INU also by including critical comments based on the direct experience of the Authors. With this aim, a full paragraph is dedicated to practical chemical experiences useful to reduce the efforts when establishing new experimental conditions. Moreover, the pharmaceutical technology is also taken in special consideration by underlining the aspects leading at the preparation of formulations based on INU. At the end of the review, a critical paragraph is intended to feed the scientists’ curiosity on this versatile polysaccharide