The hypoxia-inducible factor (HIF) is a key regulator of the transcriptional response to hypoxia. While the mechanism underpinning HIF activation is well understood, little is known about its resolution. Both the protein and the mRNA levels of HIF-1α (but not HIF-2α) were decreased in intestinal epithelial cells exposed to prolonged hypoxia. Coincident with this, microRNA (miRNA) array analysis revealed multiple hypoxia-inducible miRNAs. Among these was miRNA-155 (miR-155), which is predicted to target HIF-1α mRNA. We confirmed the hypoxic upregulation of miR-155 in cultured cells and intestinal tissue from mice exposed to hypoxia. Furthermore, a role for HIF-1α in the induction of miR-155 in hypoxia was suggested by the identification of hypoxia response elements in the miR-155 promoter and confirmed experimentally. Application of miR-155 decreased the HIF-1α mRNA, protein, and transcriptional activity in hypoxia, and neutralization of endogenous miR-155 reversed the resolution of HIF-1α stabilization and activity. Based on these data and a mathematical model of HIF-1α suppression by miR-155, we propose that miR-155 induction contributes to an isoform-specific negative-feedback loop for the resolution of HIF-1α activity in cells exposed to prolonged hypoxia, leading to oscillatory behavior of HIF-1α-dependent transcription.

Alginate is an excellent biodegradable and renewable material that is already used for a broad range of industrial applications, including advanced fields, such as biomedicine and bioengineering, due to its excellent biodegradable and biocompatible properties. This biopolymer can be produced from brown algae or a microorganism culture. This review presents the principles, chemical structures, gelation properties, chemical interactions, production, sterilization, purification, types, and alginate-based hydrogels developed so far. We present all of the advanced strategies used to remarkably enhance this biopolymer’s physicochemical and biological characteristics in various forms, such as injectable gels, fibers, films, hydrogels, and scaffolds. Thus, we present here all of the material engineering enhancement approaches achieved so far in this biopolymer in terms of mechanical reinforcement, thermal and electrical performance, wettability, water sorption and diffusion, antimicrobial activity, in vivo and in vitro biological behavior, including toxicity, cell adhesion, proliferation, and differentiation, immunological response, biodegradation, porosity, and its use as scaffolds for tissue engineering applications. These improvements to overcome the drawbacks of the alginate biopolymer could exponentially increase the significant number of alginate applications that go from the paper industry to the bioprinting of organs.