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Introduction: The process of laser-induced breakdown of amorphous and crystalline selenium nanoparticles (Se NPs) of various shapes during nanosecond laser fragmentation of aqueous colloidal solutions of nanoparticles with different concentrations has been studied. Methods: The methods of studying the characteristics of plasma and acoustic oscillations induced by optical breakdown are applied. The methods of assessing the concentration of hydrogen peroxide and hydroxyl radicals, the amount of long-lived reactive species of protein and 8-oxoguanine are applied. Results: It has been established that in the process of laser fragmentation of selenium nanoparticles at a wavelength of 532 nm, corresponding to the maximum absorption of selenium, the highest probability of breakdown, the number of plasma flashes, their luminosity and the amplitude of acoustic signals are achieved at concentrations of the order of 109 NPs/mL. It has been shown that the use of selenium nanoparticles of various shapes and structures leads to a change in the photoacoustic signal during laser-induced breakdown. When crystalline selenium nanoparticles are irradiated, the intensity of the photoacoustic response during breakdown turns out to be greater (1.5 times for flash luminosity and 3 times for acoustics) than when amorphous particles are irradiated at the same concentration. It has been shown that selenium nanoparticles exhibit significant antioxidant properties. Selenium nanoparticles effectively prevent the formation of reactive oxygen species (ROS) during water radiolysis, eliminate radiation-induced long-lived reactive species of protein, and reduce the radiation-chemical yield of a key marker of oxidative DNA damage - 8-oxoguanine. Discussion: In general, the intensity of processes occurring during laser fragmentation of amorphous and crystalline selenium nanoparticles differs significantly. The antioxidant properties are more pronounced in amorphous selenium nanoparticles compared to crystalline selenium nanoparticles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Simakin, Baimler, Dikovskaya, Kazantseva, Yanykin, Voronov, Uvarov, Astashev, Sarimov, Ivanov, Bruskov and Kozlov.)

Catalytic antibodies, or abzymes, are capable of not only binding but also hydrolyzing various proteins. Previously, an increase in the level of myelin basic protein (MBP)-hydrolyzing activity of antibodies was shown in patients with a number of neurological and mental disorders, including schizophrenia. Furthermore, antipsychotic therapy is known to induce a change in cytokine levels in patients with schizophrenia, which affects regulation of the immune response and inflammatory status. This study investigated the influence of typical and atypical antipsychotics on catalytic antibody activity and the 10 major pro- and anti-inflammatory serum cytokine levels. The study included 40 patients with schizophrenia: 15 treated with first-generation antipsychotics and 25 treated with atypical antipsychotics for 6 weeks. It was found that treatment with atypical antipsychotics changed the levels of some pro-inflammatory cytokines. Antipsychotic therapy also caused a significant decrease in MBP-hydrolyzing activity in patients with schizophrenia ( p = 0.0002), and associations of catalytic activity with interleukins were observed.

Extracellular vesicles (EVs) as membrane structures of cellular origin participating in intercellular communication are involved in the molecular mechanisms of the development of various variants of polyneuropathy. Taking into account the increasing role of the protein corona of EVs and protein-protein interactions on the surface of EVs in the pathogenesis of various diseases, we focused our attention in this review on the role of intravesicular proteins and the protein corona of EVs in the development of chemotherapy-induced polyneuropathy (CIPN). It has been shown that EVs are effectively internalized by the mechanisms of endocytosis and macropinocytosis by neurocytes and glial cells, carry markers of insulin resistance, functionally active proteins (receptors, cytokines, enzymes), and may be involved in the pathogenesis of CIPN. The mechanisms of CIPN associated with the EVs protein corona can be related with the accumulation of heavy chains of circulating IgG in it. G-class immunoglobulins in EVs are likely to have myelin hydrolyzing, superoxide dismutase, and oxidoreductase enzymatic activities. Moreover, circulating IgG-loaded EVs are a place for complement activation that can lead to membrane attack complex deposition in neuroglia and neurons. The mechanisms of CIPN development that are not associated with IgG in the EVs protein corona are somehow related to the fact that many anticancer drugs induce apoptosis of tumor cells, neurons, and neuroglial cells by various mechanisms. This process may be accompanied by the secretion of EVs with modified cargo (HSPs, 20S proteasomes, miRNAs)., Competing Interests: The authors declare no conflict of interest.

Numerous studies indicate the involvemen of oxidative stress in the pathogenesis of schizophrenia. It has been shown that the serum pool of antibodies in patients with schizophrenia contains catalytically active antibodies (abzymes) that have a wide range of activities, including redox properties. In the present work, the effects of IgGs-having oxidoreductase activities-isolated from the serum of patients with schizophrenia and healthy individuals were studied in vitro. The IgGs were purified by affinity chromatography followed by an SDS-PAGE analysis of homogeneity in a 4-18% gradient gel. The catalase and superoxide dismutase (SOD) activities of the IgGs were measured spectrophotometrically using a kinetic module. Human neuroblastoma SH-SY5Y cells were cultured with IgG at a final concentration of 0.2 mg/mL for 24 h. In a parallel experiment, tert -butyl hydroperoxide was used as an oxidative stressor. The number of dead cells after incubation was determined with fluorescent dyes, propidium iodide and Hoechst, by high-throughput screening on the CellInsight CX7 platform. A cytotoxic effect of the IgG from the schizophrenia patients on SH-SY5Y cells was detected after 24 h incubation. A correlation was found between the SOD activity of the IgGs and IgG-induced cell death. Under the induced oxidative stress, the cytotoxic effect of the IgG from the patients with schizophrenia on the SH-SY5Y cell line was five times stronger. Meanwhile, the IgG from the healthy individuals exerted a cytoprotective effect on the cultured cells, accompanied by high catalase activity. Thus, the observed influence on cell viability depends on the catalytic properties of the abzymes.

This study aimed to evaluate the superoxide dismutase (SOD) activity of IgG in patients with schizophrenia. After signing informed consent, we included 67 patients with schizophrenia (34 people with acute schizophrenia and 33 individuals were on outpatient treatment in therapeutic remission) and 14 healthy volunteers. IgGs from blood serum were isolated by affinity chromatography. SOD activity of antibodies was determined spectrophotometrically. We have shown for the first time that IgGs from patients with schizophrenia have SOD activity and this activity is an intrinsic property of antibodies. The maximum increase in SOD activity was registered in the group of patients in therapeutic remission compared with acute schizophrenia ( p = 0.005) and in healthy individuals ( p = 0.001). Based on the data of inhibitory analysis using a specific SOD inhibitor enzyme, triethylenetetramine (TETA), we can assume that the mechanism of the SOD activity of IgG is similar to the mechanism of classical enzyme catalysis. According to the kinetic analysis, the affinity of the IgGs to the substrate is higher than that of the classical SOD enzyme.

The pathogenesis of bipolar affective disorder is associated with immunological imbalances, a general pro-inflammatory status, neuroinflammation, and impaired white matter integrity. Myelin basic protein (MBP) is one of the major proteins in the myelin sheath of brain oligodendrocytes. For the first time, we have shown that IgGs isolated from sera of bipolar patients can effectively hydrolyze human myelin basic protein (MBP), unlike other test proteins. Several stringent criteria were applied to assign the studied activity to serum IgG. The level of MBP-hydrolyzing activity of IgG from patients with bipolar disorder was statistically significantly 1.6-folds higher than that of healthy individuals. This article presents a detailed characterization of the catalytic properties of MBP-hydrolyzing antibodies in bipolar disorder, including the substrate specificity, inhibitory analysis, pH dependence of hydrolysis, and kinetic parameters of IgG-dependent MBP hydrolysis, providing the heterogeneity of polyclonal MBP-hydrolyzing IgGs and their difference from canonical proteases. The ability of serum IgG to hydrolyze MBP in bipolar disorder may become an additional link between the processes of myelin damage and inflammation.

Schizophrenia is recognized to be a highly heterogeneous disease at various levels, from genetics to clinical manifestations and treatment sensitivity. This heterogeneity is also reflected in the variety of oxidative stress-related mechanisms contributing to the phenotypic realization and manifestation of schizophrenia. At the molecular level, these mechanisms are supposed to include genetic causes that increase the susceptibility of individuals to oxidative stress and lead to gene expression dysregulation caused by abnormal regulation of redox-sensitive transcriptional factors, noncoding RNAs, and epigenetic mechanisms favored by environmental insults. These changes form the basis of the prooxidant state and lead to altered redox signaling related to glutathione deficiency and impaired expression and function of redox-sensitive transcriptional factors (Nrf2, NF- κ B, FoxO, etc.). At the cellular level, these changes lead to mitochondrial dysfunction and metabolic abnormalities that contribute to aberrant neuronal development, abnormal myelination, neurotransmitter anomalies, and dysfunction of parvalbumin-positive interneurons. Immune dysfunction also contributes to redox imbalance. At the whole-organism level, all these mechanisms ultimately contribute to the manifestation and development of schizophrenia. In this review, we consider oxidative stress-related mechanisms and new treatment perspectives associated with the correction of redox imbalance in schizophrenia. We suggest that not only antioxidants but also redox-regulated transcription factor-targeting drugs (including Nrf2 and FoxO activators or NF- κ B inhibitors) have great promise in schizophrenia. But it is necessary to develop the stratification criteria of schizophrenia patients based on oxidative stress-related markers for the administration of redox-correcting treatment., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this review., (Copyright © 2021 Evgeny A. Ermakov et al.)