Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak emerged, countless efforts are being made worldwide to understand the molecular mechanisms underlying the coronavirus disease 2019 (COVID-19) in an attempt to identify the specific clinical characteristics of critically ill COVID-19 patients involved in its pathogenesis and provide therapeutic alternatives to minimize COVID-19 severity. Recently, COVID-19 has been closely related to sepsis, which suggests that most deceases in intensive care units (ICU) may be a direct consequence of SARS-CoV-2 infection-induced sepsis. Understanding oxidative stress and the molecular inflammation mechanisms contributing to COVID-19 progression to severe phenotypes such as sepsis is a current clinical need in the effort to improve therapies in SARS-CoV-2 infected patients. This article aims to review the molecular pathogenesis of SARS-CoV-2 and its relationship with oxidative stress and inflammation, which can contribute to sepsis progression. We also provide an overview of potential antioxidant therapies and active clinical trials that might prevent disease progression or reduce its severity.

Glutathione (GSH) is a linchpin of cellular defences in plants and animals with physiologically-important roles in the protection of cells from biotic and abiotic stresses. Moreover, glutathione participates in numerous metabolic and cell signalling processes including protein synthesis and amino acid transport, DNA repair and the control of cell division and cell suicide programmes. While it is has long been appreciated that cellular glutathione homeostasis is regulated by factors such as synthesis, degradation, transport, and redox turnover, relatively little attention has been paid to the influence of the intracellular partitioning on glutathione and its implications for the regulation of cell functions and signalling. We focus here on the functions of glutathione in the nucleus, particularly in relation to physiological processes such as the cell cycle and cell death. The sequestration of GSH in the nucleus of proliferating animal and plant cells suggests that common redox mechanisms exist for DNA regulation in G1 and mitosis in all eukaryotes. We propose that glutathione acts as "redox sensor" at the onset of DNA synthesis with roles in maintaining the nuclear architecture by providing the appropriate redox environment for the DNA replication and safeguarding DNA integrity. In addition, nuclear GSH may be involved in epigenetic phenomena and in the control of nuclear protein degradation by nuclear proteasome. Moreover, by increasing the nuclear GSH pool and reducing disulfide bonds on nuclear proteins at the onset of cell proliferation, an appropriate redox environment is generated for the stimulation of chromatin decompaction. This article is part of a Special Issue entitled Cellular functions of glutathione.

Lafora disease (LD) is a rare, fatal form of progressive myoclonus epilepsy. The molecular basis of this devastating disease is still poorly understood and no treatment is available yet, which leads to the death of the patients around 10 years from the onset of the first symptoms. The hallmark of LD is the accumulation of insoluble glycogen-like inclusions in the brain and peripheral tissues, as a consequence of altered glycogen homeostasis. In addition, other determinants in the pathophysiology of LD have been suggested, such as proteostasis impairment, with the reduction in autophagy, and oxidative stress, among others. In order to gain a general view of the genes involved in the pathophysiology of LD, in this work, we have performed RNA-Seq transcriptome analyses of whole-brain tissue from two independent mouse models of the disease, namely Epm2a-/-and Epm2b-/-mice, at different times of age. Our results provide strong evidence for three major facts: first, in both models of LD, we found a common set of upregulated genes, most of them encoding mediators of inflammatory response; second, there was a progression with the age in the appearance of these inflammatory markers, starting at three months of age; and third, reactive glia was responsible for the expression of these inflammatory genes. These results clearly indicate that neuroinflammation is one of the most important traits to be considered in order to fully understand the pathophysiology of LD, and define reactive glia as novel therapeutic targets in the disease.

Epigenetic modifications and regulators represent potential molecular elements which control relevant physiological and pathological features, thereby contributing to the natural history of human disease. These epigenetic modulators can be employed as disease biomarkers, since they show several advantages and provide information about gene function, thus explaining differences among patient endophenotypes. In addition, epigenetic biomarkers can incorporate information regarding the effects of the environment and lifestyle on health and disease, and monitor the effect of applied therapies. Technologies used to analyze these epigenetic biomarkers are constantly improving, becoming much easier to use. Laboratory professionals can easily acquire experience and techniques are becoming more affordable. A high number of epigenetic biomarker candidates are being continuously proposed, making now the moment to adopt epigenetics in the clinical laboratory and convert epigenetic marks into reliable biomarkers. In this review, we describe some current promising epigenetic biomarkers and technologies being applied in clinical practice. Furthermore, we will discuss some laboratory strategies and kits to accelerate the adoption of epigenetic biomarkers into clinical routine. The likelihood is that over time, better markers will be identified and will likely be incorporated into future multi-target assays that might help to optimize its application in a clinical laboratory. This will improve cost-effectiveness, and consequently encourage the development of theragnosis and the application of precision medicine.

Histone H3 senses cellular redox changes through glutathionylation of Cys, which increases during cell proliferation and decreases during aging. Glutathionylation of histone H3 affects nucleosome stability structure leading to a more open chromatin structure.

Degradation of tissue samples limits performing RNA-based molecular studies, but little is known about the potential usefulness of samples of compromised quality for studies focused on miRNAs. In this work we analyze a series of cryopreserved tissue samples (n = 14), frozen samples that underwent a severe thawing process (n = 10), and their paired formalin-fixed paraffin-embedded (FFPE) tissue samples (n = 24) from patients with breast cancer obtained during primary surgical resection and collected in 2011. Quality and integrity analyses of the total and small fraction of RNA were carried out. Recovery of specific RNA molecules (miRNAs hsa-miR-21, hsa-miR-125b, and hsa-miR-191; snoRNA RNU6B; and mRNAs GAPDH and HPRT1) was also analyzed by quantitative RT-PCR. Our results suggest that visualisation of the small RNA electrophoretic profiles obtained using the Agilent 2100 bioanalyzer makes it possible to differentiate between the three groups of samples (optimally frozen, thawed, and FFPE). We demonstrate that specific miRNA molecules can be similarly recovered from different tissue sample sources, which supports their high degree of stability. We conclude that miRNAs are robustly detected irrespective of the quality of the tissue sample. In this regard, a word of caution should be raised before degraded samples are discarded: although prior quality assessment of the biological material to be analyzed is recommended, our work demonstrates that degraded tissue samples are also suitable for miRNA studies.

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