New Insights into Oxidative and Reductive Stress Responses and Their Relation to the Anticancer Activity of Selenium-Containing Compounds as Hydrogen Selenide Donors.

Redox balance is important for the homeostasis of normal cells, but also for the proliferation, progression, and survival of cancer cells. Both oxidative and reductive stress can be harmful to cells. In contrast to oxidative stress, reductive stress and the therapeutic opportunities underlying the mechanisms of reductive stress in cancer, as well as how cancer cells respond to reductive stress, have received little attention and are not as well characterized. Therefore, there is recent interest in understanding how selective induction of reductive stress may influence therapeutic treatment and disease progression in cancer. There is also the question of how cancer cells respond to reductive stress. Selenium compounds have been shown to have chemotherapeutic effects against cancer, and their anticancer mechanism is thought to be related to the formation of their metabolites, including hydrogen selenide (H2Se), which is a highly reactive and reducing molecule. Here, we highlight recent reports on the molecular mechanism of how cells recognize and respond to oxidative and reductive stress (1) and the mechanisms through which different types of selenium compounds can generate H2Se (2) and thus selectively affect reductive stress under controlled conditions, which may be important for their anticancer effects.

Carotenoids from Marine Sources as a New Approach in Neuroplasticity Enhancement.

An increasing number of people experience disorders related to the central nervous system (CNS). Thus, new forms of therapy, which may be helpful in repairing processes' enhancement and restoring declined brain functions, are constantly being sought. One of the most relevant physiological processes occurring in the brain for its entire life is neuroplasticity. It has tremendous significance concerning CNS disorders since neurological recovery mainly depends on restoring its structural and functional organization. The main factors contributing to nerve tissue damage are oxidative stress and inflammation. Hence, marine carotenoids, abundantly occurring in the aquatic environment, being potent antioxidant compounds, may play a pivotal role in nerve cell protection. Furthermore, recent results revealed another valuable characteristic of these compounds in CNS therapy. By inhibiting oxidative stress and neuroinflammation, carotenoids promote synaptogenesis and neurogenesis, consequently presenting neuroprotective activity. Therefore, this paper focuses on the carotenoids obtained from marine sources and their impact on neuroplasticity enhancement.

Circulating miRNAs as Potential Biomarkers Distinguishing Relapsing-Remitting from Secondary Progressive Multiple Sclerosis. A Review.

Multiple sclerosis (MS) is a debilitating neurodegenerative, highly heterogeneous disease with a variable course. The most common MS subtype is relapsing-remitting (RR), having interchanging periods of worsening and relative stabilization. After a decade, in most RR patients, it alters into the secondary progressive (SP) phase, the most debilitating one with no clear remissions, leading to progressive disability deterioration. Among the greatest challenges for clinicians is understanding disease progression molecular mechanisms, since RR is mainly characterized by inflammatory processes, while in SP, the neurodegeneration prevails. This is especially important because distinguishing RR from the SP subtype early will enable faster implementation of appropriate treatment. Currently, the MS course is not well-correlated with the biomarkers routinely used in clinical practice. Despite many studies, there are still no reliable indicators correlating with the disease stage and its activity degree. Circulating microRNAs (miRNAs) may be considered valuable molecules for the MS diagnosis and, presumably, helpful in predicting disease subtype. MiRNA expression dysregulation is commonly observed in the MS course. Moreover, knowledge of diverse miRNA panel expression between RRMS and SPMS may allow for deterring disability progression through successful treatment. Therefore, in this review, we address the current state of research on differences in miRNA panel expression between the phases.

Th17-Related Cytokines as Potential Discriminatory Markers between Neuromyelitis Optica (Devic's Disease) and Multiple Sclerosis-A Review.

Multiple sclerosis (MS) and Devic's disease (NMO; neuromyelitis optica) are autoimmune, inflammatory diseases of the central nervous system (CNS), the etiology of which remains unclear. It is a serious limitation in the treatment of these diseases. The resemblance of the clinical pictures of these two conditions generates a partial possibility of introducing similar treatment, but on the other hand, a high risk of misdiagnosis. Therefore, a better understanding and comparative characterization of the immunopathogenic mechanisms of each of these diseases are essential to improve their discriminatory diagnosis and more effective treatment. In this review, special attention is given to Th17 cells and Th17-related cytokines in the context of their potential usefulness as discriminatory markers for MS and NMO. The discussed results emphasize the role of Th17 immune response in both MS and NMO pathogenesis, which, however, cannot be considered without taking into account the broader perspective of immune response mechanisms.

Interplay between BRCA1 and GADD45A and Its Potential for Nucleotide Excision Repair in Breast Cancer Pathogenesis.

A fraction of breast cancer cases are associated with mutations in the BRCA1 (BRCA1 DNA repair associated, breast cancer type 1 susceptibility protein) gene, whose mutated product may disrupt the repair of DNA double-strand breaks as BRCA1 is directly involved in the homologous recombination repair of such DNA damage. However, BRCA1 can stimulate nucleotide excision repair (NER), the most versatile system of DNA repair processing a broad spectrum of substrates and playing an important role in the maintenance of genome stability. NER removes carcinogenic adducts of diol-epoxy derivatives of benzo[α]pyrene that may play a role in breast cancer pathogenesis as their accumulation is observed in breast cancer patients. NER deficiency was postulated to be intrinsic in stage I of sporadic breast cancer. BRCA1 also interacts with GADD45A (growth arrest and DNA damage-inducible protein GADD45 alpha) that may target NER machinery to actively demethylate genome sites in order to change the expression of genes that may be important in breast cancer. Therefore, the interaction between BRCA1 and GADD45 may play a role in breast cancer pathogenesis through the stimulation of NER, increasing the genomic stability, removing carcinogenic adducts, and the local active demethylation of genes important for cancer transformation.

Silica-covered star-shaped Au-Ag nanoparticles as new electromagnetic nanoresonators for Raman characterisation of surfaces.

One of the tools used for determining the composition of surfaces of various materials is shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS). SHINERS is a modification of "standard" surface-enhanced Raman spectroscopy (SERS), in which, before Raman spectra are recorded, the surfaces analysed are covered with a layer of plasmonic nanoparticles protected by a very thin layer of a transparent dielectric. The plasmonic cores of the core-shell nanoparticles used in SHINERS measurements generate a local enhancement of the electric field of the incident electromagnetic radiation, whereas the transparent coatings prevent the metal cores from coming into direct contact with the material being analysed. In this contribution, we propose a new type of SHINERS nanoresonators that contain spiky, star-shaped metal cores (produced from a gold/silver alloy). These spiky, star-shaped Au-Ag nanoparticles have been covered by a layer of silica. The small radii of the ends of the tips of the spikes of these plasmonic nanostructures make it possible to generate a very large enhancement of the electromagnetic field there, with the result that such SHINERS nanoresonators are significantly more efficient than the standard semi-spherical nanostructures. The Au-Ag alloy nanoparticles were synthesised by the reduction of a solution containing silver nitrate and chloroauric acid by ascorbic acid. The final geometry of the nanostructures thus formed was controlled by changing the ratio between the concentrations of AuCl4- and Ag+ ions. The shape of the synthesised star-shaped Au-Ag nanoparticles does not change significantly during the two standard procedures for depositing a layer of silica (by the decomposition of sodium silicate or the decomposition of tetraethyl orthosilicate).