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The therapeutic potential of redox-active nanoscale materials as antioxidant- or reactive oxygen species (ROS)-inducing agents was intensely studied. Herein, we demonstrate that the synthesized and characterized GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles, which have been already shown to have redox-active, anti-inflammatory, antibacterial, and wound healing properties, both in vitro and in vivo, worsen oxidative stress of L929 cells triggered by hydrogen peroxide or tert-butyl hydroperoxide (tBuOOH) at the concentrations that are safe for intact L929 cells. This effect was observed upon internalization of the investigated nanosized materials and is associated with the cleavage of caspase-3 and caspase-9 without recruitment of caspase-8. Such changes in the caspase cascade indicate activation of the intrinsic caspase-9-dependent mitochondrial but not the extrinsic death, receptor-mediated, and caspase-8-dependent apoptotic pathway. The GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticle-induced apoptosis of oxidatively compromised L929 cells is mediated by ROS overgeneration, Ca2+ overload, endoplasmic reticulum stress-associated JNK (c-Jun N-terminal kinase), and DNA damage-inducible transcript 3 (DDIT3). Our findings demonstrate that GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles aggravate the oxidative stress-induced damage to L929 cells, indicating that they might potentially be applied as anti-cancer agents. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs) with reactive oxygen species (ROS)-regulating ability have recently attracted great attention as promising agents for nanomedicine. In the present study, we have analyzed the effects of TiO2 defect structure related to the presence of stoichiometric (Ti4+) and non-stoichiometric (Ti3+ and Ti2+) titanium ions in the crystal lattice and TiO2 NPs aggregation ability on H2O2- and tert-butyl hydroperoxide (tBOOH)-induced ROS production in L929 cells. Synthesized TiO2-A, TiO2-B, and TiO2-C NPs with varying Ti3+(Ti2+) content were characterized by x-ray powder diffraction, transmission electron microscopy, small-angle x-ray scattering, x-ray photoelectron spectroscopy, and optical spectroscopy methods. Given the role of ROS-mediated toxicity for metal oxide NPs, L929 cell viability and changes in the intracellular ROS levels in H2O2- and tBOOH-treated L929 cells incubated with TiO2 NPs have been evaluated. Our research shows that both the amount of non-stoichiometric Ti3+ and Ti2+ ions in the crystal lattice of TiO2 NPs and NPs aggregative behavior affect their catalytic activity, in particular, H2O2 decomposition and, consequently, the efficiency of aggravating H2O2- and tBOOH-induced oxidative damage to L929 cells. TiO2-A NPs reveal the strongest H2O2 decomposition activity aligning with their less pronounced additional effects on H2O2-treated L929 cells due to the highest amount of Ti3+(Ti2+) ions. TiO2-C NPs with smaller amounts of Ti3+ ions and a tendency to aggregate in water solutions show lower antioxidant activity and, consequently, some elevation of the level of ROS in H2O2/tBOOH-treated L929 cells. Our findings suggest that synthesized TiO2 NPs capable of enhancing ROS generation at concentrations non-toxic for normal cells, which should be further investigated to assess their possible application in nanomedicine as ROS-regulating pharmaceutical agents. [ABSTRACT FROM AUTHOR]

Introduction: Human chemerin is an adipokine that regulates chemotaxis, inflammation, and glucose metabolism. In addition, accumulating evidence suggests that chemerin promotes apoptosis, autophagy, and pyroptosis. However, there are no data on its impact on eryptosis. The current study aimed to analyze the effects of human active Glu-Ser chemerin on eryptosis in vitro. Materials and Methods: Human chemerin 0-2-10-50 µg/mL was incubated for 24 h with human erythrocytes (hematocrit 0.4%) obtained from eight healthy individuals. Flow cytometry-based determination of phospholipid scrambling, reactive oxygen species (ROS) production, and intracellular Ca levels was performed. To supplement data on ROS and Ca signaling in chemerin-mediated eryptosis, incubation in the presence or absence of antioxidants vitamin C and N-acetylcysteine and Ca-binding agent EGTA was carried out, respectively. Confocal microscopy-based techniques were used to detect reactive nitrogen species (RNS) generation, involvement of caspase-3 and caspase-8, as well as the state of lipid order in cell membranes of erythrocytes exposed to human Glu-Ser chemerin. Results: Our observations suggest that human Glu-Ser chemerin had no impact on eryptosis parameters at 2 µg/mL. However, chemerin stimulated phosphatidylserine externalization, ROS production, and Ca accumulation at higher concentrations suggesting activation of eryptosis. Ca uptake turned out to be at least partly required for chemerin-mediated eryptosis. Chemerin-mediated erythrotoxicity was additionally mediated by RNS, caspase-3, and caspase-8. Moreover, Glu-Ser chemerin promoted reduction in the liquid-ordered phase of cell membranes in erythrocytes. Conclusions: The present study first discloses that human chemerin can induce eryptosis via Ca-dependent mechanisms at concentrations noticeably exceeding circulating levels. Thus, chemerin-induced eryptosis can hardly contribute to eryptosis-mediated anemia in diseases associated with enhanced levels of chemerin in blood. [ABSTRACT FROM AUTHOR]

Aim. In this study, blood compatibility of ZnO nanoparticles-polymer nanocomplex (D-PAA/ZnONPs( SO 4 2 − )) synthesized in situ into dextran-graft-polyacrylamide (D-PAA) using zinc sulphate as a precursor was tested using hemolysis, osmotic fragility and eryptosis assays. Materials and methods. Dose-dependent ability to induce eryptosis was assessed following 24 h incubation at concentrations of 0–800 mg l−1 analyzing hallmarks of eryptosis (cell shrinkage and phosphatidylserine externalization), as well as reactive oxygen species generation. Hemolysis was detected spectrophotometrically based on hemoglobin release following exposure to the D-PAA/ZnONPs( SO 4 2 − ) nanocomplex. Osmotic fragility test (OFT) involved detection of hemolysis of red blood cells exposed to 0.2% saline solution following incubation with the D-PAA/ZnONPs( SO 4 2 − ) nanocomplex. Additional incubation of the nanocomplex in the presence or absence of either ascorbic acid or EGTA was used to reveal the implication of oxidative stress- or Ca2+-mediated mechanisms in D-PAA/ZnONPs( SO 4 2 − ) nanocomplex-induced erythrotoxicity. Results. Hemocompatibility assessment of the D-PAA/ZnONPs( SO 4 2 − ) nanocomplex revealed that it induced hemolysis and reduced resistance of erythrocytes to osmotic stress at concentrations of above 400 and 200 mg l−1, respectively. Oxidative stress- or Ca2+-mediated mechanisms were not involved in D-PAA/ZnONPs( SO 4 2 − ) nanocomplex-induced hemolysis. Strikingly, the D-PAA/ZnONPs( SO 4 2 − ) nanocomplex did not promote cell membrane scrambling, cell shrinkage and oxidative stress in red blood cells following the direct exposure for 24 h. Thus, the D-PAA/ZnONPs( SO 4 2 − ) nanocomplex did not induce eryptosis in vitro. Eryptosis is generally considered to occur earlier than hemolysis in response to stress in order to prevent hemolytic cell death. Counterintuitively, our data suggest that hemolysis can be triggered by nanomaterials prior to eryptosis indicating that eryptosis and hemolysis assays should be used in combination for testing blood compatibility of nanomaterials. Conclusions. The D-PAA/ZnONPs( SO 4 2 − ) nanocomplex has a good hemocompatibility profile at low concentrations. Hemocompatibility testing in nanotoxicology should include both eryptosis and hemolysis assays. [ABSTRACT FROM AUTHOR]

Introduction. Rare-earth orthovanadate nanoparticles (ReVO4:Eu3+, Re = Gd, Y or La) are promising agents for photodynamic therapy of cancer due to their modifiable redox properties. However, their toxicity limits their application. Objective. The aim of this research was to elucidate pro-eryptotic effects of GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles with identification of underlying mechanisms of eryptosis induction and to determine their pharmacological potential in eryptosis-related diseases. Methods. Blood samples (n = 9) were incubated for 24 h with 0–10–20–40–80 mg l−1 GdVO4:Eu3+ or LaVO4:Eu3+ nanoparticles, washed and used to prepare erythrocyte suspensions to analyze the cell membrane scrambling (annexin-V-FITC staining), cell shrinkage (forward scatter signaling), reactive oxygen species (ROS) generation through 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) staining and intracellular Ca2+ levels via FLUO4 AM staining by flow cytometry. Internalization of europium-enabled luminescent GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles was assessed by confocal laser scanning microscopy. Results. Both nanoparticles triggered eryptosis at concentrations of 80 mg l−1. ROS-mediated mechanisms were not involved in rare-earth orthovanadate nanoparticles-induced eryptosis. Elevated cytosolic Ca2+ concentrations were revealed even at subtoxic concentrations of nanoparticles. LaVO4:Eu3+ nanoparticles increased intracellular calcium levels in a more pronounced way compared with GdVO4:Eu3+ nanoparticles. Our data disclose that the small-sized (15 nm) GdVO4:Eu3+ nanoparticles were internalized after a 24 h incubation, while the large-sized (∼30 nm) LaVO4:Eu3+ nanoparticles were localized preferentially around erythrocytes. Conclusions. Both internalized GdVO4:Eu3+ and non-internalized LaVO4:Eu3+ nanoparticles (80 mg l−1) promote eryptosis of erythrocytes after a 24 h exposure in vitro via Ca2+ signaling without involvement of oxidative stress. Eryptosis is a promising model for assessing nanotoxicity. [ABSTRACT FROM AUTHOR]

The issue of limited social interactions, household possibilities, and self-care gain increasing social importance. Under the general term of ergotherapy interventions, scientists use a wide array of different approaches used separately or in combination. In particular, this article discusses the ergotherapeutical intervention where we analyzed the stages, goals, directions, and principles of ergotherapy that have a positive effect on the social adaptation of children suffering from Down syndrome. We have found that ergotherapy is aimed at helping children suffering from Down syndrome to build or improve basic social or household skills through a series of special exercises, which will allow them to achieve the maximum level of independence and self-sufficiency in life. It was also identified that the important role in the program of ergotherapy is dedicated to a game, which is often the only way in which children can express themselves because of their specific needs. Ergotherapy was found to be one of the methods if holistic rehabilitation for children with Down syndrome, since its main goal is to develop independence and socialization. The positive effect such therapy has when performed both in specialized institutions and at home is undoubted. Apart from that, it should be noted that there is no established correlation between the number of exercises and their ultimate effect. Although a lot of research sheds light on some of the aspects of the issue in question, there is no holistic picture of how to organize practical social activities for children with Down syndrome during the ergotherapy sessions. However, the systematic study of other research indicated the insufficient evidence basis of the majority of methods as well as the low quality of the mentioned research. [ABSTRACT FROM AUTHOR]

Recent studies have shown an increase in various disorders in the health of young people. Analysis of the structure of morbidities shows that the diseases of the cardiovascular system are placed on the top, among which the syndrome of autonomic dysfunction in students is most common. Currently, autonomic disorders are one of the most pressing problems in the health of young people due to the significant spread of this pathology, which is 20 to 60% of the total incidence of people of all ages, according to various authors. The most common disorders of the autonomic nervous system occur among adolescents and students, due to hormonal changes in the body during puberty, stress on the functioning of various organs and systems, and significant mental and physical overload. Despite the fact that the syndrome of autonomic dysfunction is considered as a prognostically favourable functional disease at this age, many scientists talk about a fairly high risk of its transition to cardiovascular disease, in particular, hypertension. Among the most important etiological factors of the syndrome of autonomic dysfunction are hereditary predisposition, which causes this pathology of a constitutional nature, i.e. hereditary or congenital syndrome. The study found that the use of basic means of physical therapy along with the technique of Thai acupressure and Nordic walking improved students' wellbeing and basic vital signs. The use of this technique along with Thai acupressure and Nordic walking allowed us to accurately assess its effectiveness and analyse the dynamics of the selected indicators. Study participants: 48 students of the main group with autonomic dysfunction syndrome were involved. The article reflects a positive change in the functional status of the body and the improvement of general blood circulation and the overall beneficial effect on the nervous and cardiovascular systems. Conclusions: the chosen programme of physical therapy along with Thai acupressure and Nordic walking helps overcome the syndrome of autonomic dysfunction and improves the recovery processes and overall health. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs) with reactive oxygen species (ROS)-regulating ability have recently attracted great attention as promising agents for nanomedicine. In the present study, we have analyzed the effects of TiO 2 defect structure related to the presence of stoichiometric (Ti 4+ ) and non-stoichiometric (Ti 3+ and Ti 2+ ) titanium ions in the crystal lattice and TiO 2 NPs aggregation ability on H 2 O 2 - and tert-butyl hydroperoxide (tBOOH)-induced ROS production in L929 cells. Synthesized TiO 2 -A, TiO 2 -B, and TiO 2 -C NPs with varying Ti 3+ (Ti 2+ ) content were characterized by x-ray powder diffraction, transmission electron microscopy, small-angle x-ray scattering, x-ray photoelectron spectroscopy, and optical spectroscopy methods. Given the role of ROS-mediated toxicity for metal oxide NPs, L929 cell viability and changes in the intracellular ROS levels in H 2 O 2 - and tBOOH-treated L929 cells incubated with TiO 2 NPs have been evaluated. Our research shows that both the amount of non-stoichiometric Ti 3+ and Ti 2+ ions in the crystal lattice of TiO 2 NPs and NPs aggregative behavior affect their catalytic activity, in particular, H 2 O 2 decomposition and, consequently, the efficiency of aggravating H 2 O 2 - and tBOOH-induced oxidative damage to L929 cells. TiO 2 -A NPs reveal the strongest H 2 O 2 decomposition activity aligning with their less pronounced additional effects on H 2 O 2 -treated L929 cells due to the highest amount of Ti 3+ (Ti 2+ ) ions. TiO 2 -C NPs with smaller amounts of Ti 3+ ions and a tendency to aggregate in water solutions show lower antioxidant activity and, consequently, some elevation of the level of ROS in H2O2/tBOOH-treated L929 cells. Our findings suggest that synthesized TiO 2 NPs capable of enhancing ROS generation at concentrations non-toxic for normal cells, which should be further investigated to assess their possible application in nanomedicine as ROS-regulating pharmaceutical agents., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Iatrogenic stress urinary incontinence (SUI) is the most common complication of surgical treatment of prostate cancer, regardless of operative approach, and has a major impact on patients' quality of life. Although SUI can occur after surgical treatment of benign prostatic hyperplasia, specifically transurethral prostate resection, laser enucleation of the prostate, and simple open prostatectomy, these therapeutic modalities play a much less significant role in the etiology of SUI. Artificial urethral sphincter (AUS) implantation is considered the standard treatment modality providing high success rates, including durable efficacy, and optimal patient satisfaction for moderate to severe urinary incontinence resulting mainly from radical prostatectomy. However, although complication rates are generally acceptably low, revision and/or explantation may be required due to mechanical failure and non-mechanical problems, specifically urethral atrophy/cuff deficient occlusion, infection, and cuff erosion. Several risk factors for AUS failure associated with a fragile, compromised urethra have been identified and these play a critical role in device cuff erosion and subsequent removal of the device. Among others, apparently the most impacting factors are irradiation, urethral stent placement, a previous AUS placement, and importantly presence of urethral stricture or prior urethroplasty. Generally, any clinical situation leading to a diseased urethra or lack of urethral integrity is associated with impaired local blood perfusion, and consequently lower success rates. The present review aims to evaluate the impact of the presence of prior urethral strictures and urethroplasty on the outcomes of AUS implantation on one hand, and vice-versa, the influence of AUS placement on later urethral stricture surgery, particularly following cuff erosion., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at: https://tau.amegroups.com/article/view/10.21037/tau-23-16/coif). The series “50 Years Anniversary of the Modern Artificial Urinary Sphincter” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)