DNA is subjected to several modifications, resulting from endogenous and exogenous sources. The cell has developed a network of complementary DNA-repair mechanisms, and in the human genome, >130 genes have been found to be involved. Knowledge about the basic mechanisms for DNA repair has revealed an unexpected complexity, with overlapping specificity within the same pathway, as well as extensive functional interactions between proteins involved in repair pathways. Unrepaired or improperly repaired DNA lesions have serious potential consequences for the cell, leading to genomic instability and deregulation of cellular functions. A number of disorders or syndromes, including several cancer predispositions and accelerated aging, are linked to an inherited defect in one of the DNA-repair pathways. Genomic instability, a characteristic of most human malignancies, can also arise from acquired defects in DNA repair, and the specific pathway affected is predictive of types of mutations, tumor drug sensitivity, and treatment outcome. Although DNA repair has received little attention as a determinant of drug sensitivity, emerging knowledge of mutations and polymorphisms in key human DNA-repair genes may provide a rational basis for improved strategies for therapeutic interventions on a number of tumors and degenerative disorders.

The protein ERp57/GRP58 is a stress-responsive protein and a component of the protein disulfide isomerase family. Its functions in the endoplasmic reticulum are well known, concerning mainly the proper folding and quality control of glycoproteins, and participation in the assembly of the major histocompatibility complex class 1. However, ERp57 is present in many other subcellular locations, where it is involved in a variety of functions, primarily suggested by its participation in complexes with other proteins and even with DNA. While in some instances these roles need to be confirmed by further studies, a great number of observations support the participation of ERp57 in signal transduction from the cell surface, in regulatory processes taking place in the nucleus, and in multimeric protein complexes involved in DNA repair.

The ERp57/PDIA3 protein is a pleiotropic member of the PDIs family and, although predominantly located in the endoplasmic reticulum (ER), has indeed been found in other cellular compartments, such as the nucleus or the cell membrane. ERp57/PDIA3 is an important research target considering it can be found in various subcellular locations. This protein is involved in many different physiological and pathological processes, and our review describes new data on its functions and summarizes some ligands identified as PDIA3-specific inhibitors.

Self-assembled nanohydrogels based on hydrophobically modified polysaccharides have been extensively studied due to their wide potential applications as drug delivery systems. In the present study, we developed and characterized self-assembling nanohydrogels based on sonicated gellan gum chains. Prednisolone (Pred), a poorly water soluble anti-inflammatory drug, was chemically conjugated to the carboxylic groups of gellan (Ge–Pred) and it was the hydrophobic moiety responsible for the self-assembling process. Ge–Pred was characterized by proton nuclear magnetic resonance spectra ( ¹H-NMR) and the cellular cytotoxicity was assessed by the MTS assay. The self-aggregation behavior in aqueous media of Ge–Pred was evaluated by the pyrene fluorescence technique and the nanohydrogels (NHs), prepared by bath sonication in water, were analyzed by dynamic light scattering (DLS) and ζ-potential. The average size of the nanohydrogels was about 300 nm and their ζ-potential values were negative. Our results showed that Ge–Pred NHs are cytocompatible, that the drug is bioavailable and, consequently, they represent an interesting and innovative carrier for prednisolone.