440 publications from this institution
Summary: Background: Progress in gene therapy depends on establishing the appropriate gene transfer methods. The most efficient vehicles for the delivery of foreign genes to the target tissues are modified adenoviruses. Methods: Adenoviral vectors of the first generation despite the high infection efficiency, have an essential drawback: They induce a strong immune response, which excludes them from clinical trials. Results: In the past few years, there have been substantial efforts to improve adenoviral vectors with particular emphasis on reducing immunological effects in the host organism. Conclusions: In this review we describe the preparation and application of gutless vectors, the most advanced and promising type of adenoviral vehicles so far. Zusammenfassung: Grundlagen: Der Erfolg einer Gentherapie hängt von der Etablierung geeigneter Gentransfermethoden ab. Die effektivsten Transportmittel für Fremdgene zum Zielgewebe vermitteln modifizierte Adenoviren. Methodik: Die erste Generation von adenoviralen Vektoren haben ungeachtet der hohen Infektiosität einen essentiellen Nachteil: sie induzieren eine starke Immunantwort, die sie von klinischen Versuchen ausschließt. Ergebnisse: In den letzten Jahren gab es verstärkte Bemühungen, die adenoviralen Vektoren zu verbessern und im Besonderen die immunologischen Effekte an dem Empfängerorganismus zu reduzieren. Schlußfolgerungen: Hier beschreiben wir die Präparation und Applikation von „Gutless”-Vektoren, den bisher bestentwickelten und vielversprechendsten adenoviralen Vektoren.
<b><i>Significance:</i></b> Skeletal muscles have a robust regenerative capacity in response to acute and chronic injuries. Muscle repair and redox homeostasis are intimately linked; increased generation of reactive oxygen species leads to cellular dysfunction and contributes to muscle wasting and progression of muscle diseases. In exemplary muscle disease, Duchenne muscular dystrophy (DMD), caused by mutations in the <i>DMD</i> gene that encodes the muscle structural protein dystrophin, the regeneration machinery is severely compromised, while oxidative stress contributes to the progression of the disease. The nuclear factor erythroid 2-related factor 2 (NRF2) and its target genes, including heme oxygenase-1 (HO-1), provide protective mechanisms against oxidative insults. <b><i>Recent Advances:</i></b> Relevant advances have been evolving in recent years in understanding the mechanisms by which NRF2 regulates processes that contribute to effective muscle regeneration. To this end, pathways related to muscle satellite cell differentiation, oxidative stress, mitochondrial metabolism, inflammation, fibrosis, and angiogenesis have been studied. The regulatory role of NRF2 in skeletal muscle ferroptosis has been also suggested. Animal studies have shown that NRF2 pathway activation can stop or reverse skeletal muscle pathology, especially when endogenous stress defence mechanisms are imbalanced. <b><i>Critical Issues:</i></b> Despite the growing recognition of NRF2 as a factor that regulates various aspects of muscle regeneration, the mechanistic impact on muscle pathology in various models of muscle injury remains imprecise. <b><i>Future Directions:</i></b> Further studies are necessary to fully uncover the role of NRF2 in muscle regeneration, both in physiological and pathological conditions, and to investigate the possibilities for development of new therapeutic modalities. <i>Antioxid. Redox Signal.</i> 38, 619-642.
Heme oxygenase-1 (HO-1) is an enzyme degrading heme to three products - ferrous ions, carbon monoxide and biliverdin. Its function extends, however, far beyond removal of pro-oxidative heme from microenvironment. During the last few decades it was proven that apart from cytoprotective and antioxidative properties HO-1 regulates also a variety of cellular processes. It exerts an impact on both innate and adaptive immune response. HO-1 accelerates development of new blood vessels in a process called angiogenesis. Moreover, it controls cell cycle and depending on a cell type increases or decreases the rate of cell division. Finally, the most recent data indicate, that HO-1 regulates also differentiation of various stem and progenitor cells. Interestingly, that aspect of HO-1 function seems also to depend on cell type. In this review, both effects and mechanisms of above-mentioned processes in different cell types are discussed.
Not only double, Janus face, but numerous appearances characterize heme oxygenase-1 (HO-1), an inducible enzyme which main role is to degrade heme. Recently, the noncanonical functions of HO-1 have particularly attracted researchers' attention. Indeed, understanding the enzyme-independent activities of HO-1 can provide additional chances for translational application of research on HO-1. In this Forum, eight reviews and two original articles describe a plethora of mechanisms in which this pleiotropic protein is involved. Further understanding of HO-1 functions is of particular significance for elucidating the pathology of various human diseases and providing rationale for novel therapies.
