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• Pub. Date : 2025
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• Pub. Date : 2025
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Methylene blue (MB) has antioxidant properties, yet its role in acute lung injury (ALI) induced by hypothermic circulatory arrest (HCA) remains unexplored. This study investigates MB’s effects and underlying regulatory mechanisms in an HCA rat model. Rats received an intravenous bolus of MB (1 mg/kg) 15 min before HCA induction. Physiological parameters were monitored, and bronchoalveolar lavage fluid (BALF) was collected 2 h postoperatively to assess total protein levels, inflammatory cells, and cytokines. Histopathological lung damage was evaluated using hematoxylin–eosin (H&E) and TUNEL staining. Inflammatory markers and oxidative stress indicators were measured via ELISA and dihydroethidium (DHE) staining. Alveolar macrophages (AMs) were isolated to analyze polarization using flow cytometry and immunofluorescence double staining. Pyroptosis in AMs was detected with Yo-Pro-1 and Hoechst 33342 staining. Additionally, Western blotting was performed to examine the nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, Nod-like receptor protein 3 (NLRP3) inflammasome, and pyroptosis-related proteins. Following HCA, rats exhibited significant blood gas abnormalities, structural lung damage, increased pathological scores, and higher apoptosis rates. However, MB mitigated these effects, improving physiological parameters and reducing lung histopathology scores. MB also lowered proinflammatory cytokine levels, increased SOD and GSH-Px activity, promoted AM polarization toward the M2 phenotype, and decreased pyroptosis. Mechanistically, MB activated the Nrf2/HO-1 pathway while inhibiting NLRP3 inflammasome activation. Notably, Nrf2 inhibitors and NLRP3 agonists weakened MB’s protective effects by promoting inflammasome activation and pyroptosis, whereas Nrf2 agonists and NLRP3 inhibitors enhanced MB’s beneficial impact. In conclusion, MB attenuates HCA-induced ALI by modulating AM polarization and pyroptosis via Nrf2/HO-1 pathway activation and NLRP3 inflammasome inhibition.

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• Pub. Date : 2025
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• Pub. Date : 2025
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• Pub. Date : 2025
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Cancer is the second-leading cause of death in developed societies. Specifically, cancers of the spine and brain come with significant therapeutic challenges. Chordomas are semi-malignant tumors that develop from embryonic residuals at the skull base (clival) or coccyx (sacral). Small tumor fragments can remain in the operation cavities during surgical resection, forming new tumor sites. This requires repeated surgeries or the application of proton-beam radiation and chemotherapy, which often do not lead to complete remission of the tumors. Hence, there is a need for novel therapeutic avenues that are not limited to killing visible tumors but can be applied after surgery to decrease chordoma recurrences. Reactive oxygen species (ROS) generated locally via novel medical gas plasma technologies are one potential approach to address this clinical problem. Previously, broad-spectrum free radicals generated by these cold physical plasmas operated at about body temperature were shown to oxidize cancer cells to the disadvantage of their growth and induce immunogenic cancer cell death (ICD), ultimately promoting anticancer immunity. This review outlines the clinical challenges of chordoma therapy, how medical gas plasma technology could serve as an adjuvant treatment modality, and potential immune-related mechanisms of action that could extend the longevity of gas plasma therapy beyond its acute local tissue effects.

• Book : 17(4)
• Pub. Date : 2025
• Page : pp.681-681
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Abstract Background Optic pathway gliomas (OPGs) are tumors in the optic nerve, chiasm, or hypothalamus, primarily affecting children. They can cause visual disturbances and increased intracranial pressure. The current treatment approach includes chemotherapy, radiotherapy, or surgery, but the optimal management strategy remains uncertain. Gamma Knife radiosurgery (GKS) has emerged as a promising option for managing OPGs, offering lower toxicity rates and improved neurocognitive function. However, the effectiveness and safety of GKS for OPGs require further investigation. A systematic review was conducted to evaluate the outcomes and potential complications of GKS for OPGs. The study aimed to assess the safety and efficacy of GKS in terms of tumor control, visual outcome, and endocrine outcome. Methods Using the related key terms, we comprehensively searched relevant articles from PubMed, Embase, Scopus, and Web of Science databases from inception to June 15, 2024. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included according to the eligibility criteria, and the relevant data were extracted. Results The current systematic review included seven studies (n = 83, 40 males and 43 females). All studies employed Gamma Knife as the radiation source, and the reported progression-free survival rates ranged from 78 to 100% during one to five years following treatment. During a one to five-year follow-up period, the preservation of visual acuity was reported to range between 77 and 92%. Furthermore, no cases of radiation necrosis or other neurological impairments were reported in the studies. Conclusion GKS appears to be a safe and effective treatment option for patients with OPGs, minimizing the risk of radiation-induced toxicity. However, further controlled studies are needed to establish the current study's findings regarding safety and efficacy.

• Book : 40(1)
• Pub. Date : 2025
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The tumor microenvironment (TME) plays a pivotal role in cancer development and progression, and comprises various cellular and non-cellular components that interact with tumor cells. Tenascin-C (TNC) is an extracellular matrix glycoprotein that is widely expressed in the cancer stroma and influences critical processes, such as cell adhesion, migration, and immune modulation. This review examines the multifaceted roles of TNC in different TMEs, including the mechanical, immune, and metabolic microenvironments, as well as the radiation microenvironment (RME). In the context of the mechanical microenvironment, TNC actively participates in extracellular matrix remodeling, thereby facilitating tumor invasion. Notably, TNC exhibits immunosuppressive effects on T cells and promotes the recruitment of immunosuppressive cells within the immune microenvironment. Furthermore, TNC is implicated in the tumor hypoxia response, glucose metabolism reprogramming, and regulation of pH balance, underscoring its role in the metabolic microenvironment. Intriguingly, TNC also influences radiosensitivity within RME. This review also explores the potential of TNC as a biomarker for cancer prognosis and as a target for therapeutic interventions. By integrating recent advances in single-cell sequencing and spatial omics, we propose innovative strategies for leveraging TNC in personalized cancer therapy. Future research directions are discussed, focusing on distinct isoforms of TNC, their interaction networks, and their roles in radiotherapy efficacy. This comprehensive analysis underscores the importance of TNC in understanding tumor dynamics and improving cancer treatment outcomes.

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• Pub. Date : 2025
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Introduction. A significant shortage of high-quality donor organs remains one of the most pressing challenges, especially when it comes to extended criteria donors or asystolic donors. The solution to this problem arises at the intersection of surgical skill, advanced biomedical technologies and a deep understanding of the mechanisms of ischemia-reperfusion injury (IRI). Objective. This study was carried out to substantiate and refine the technique of extracorporeal ex-vivo perfusion of a liver graft on an animal model using the Ex-Stream perfusion apparatus for extracorporeal oxygenation according to TU 32.50.21-002-75538036-2020 (RU holder Transbiotek LLC, St. Petersburg, Russia, manufacturer Biosoft-M LLC, Moscow, Russia). Materials and methods. The study was conducted on male pigs weighing 15–30 kg (n = 5). The study is based on the analysis of the results of hypothermic oxygenated perfusion of the liver transplant in a vivarium using a cardiopulmonary bypass apparatus. The study was conducted according to the following protocol: the donor liver was removed from the animal with the formation of a temporary venovenous bypass, pharmaco-cold preservation of the organ using the Ex-Stream apparatus and its subsequent replantation. Results. The following results were obtained in a series of 5 observations. Tissue damage markers (AST, ALT, LDH, GGTP) showed a gradual increase in their level in the perfusate over the course of ischemia. The average values of AST and ALT increased by 2-3 times, LDH - by 1.5-2 times, and GGTP - by 1.2-1.5 times compared to the initial values. The level of malondialdehyde, reflecting oxidative stress, increased by an average of 30–40% by the end of the experiment, while the level of glutathione decreased by 20–25%. Concentrations of proinflammatory cytokines (TNF-α, IL-6, IL-1β) in the perfusate increased 2–4 times compared to baseline values, indicating the development of an inflammatory response. Microscopic examination with hematoxylin and eosin staining revealed signs of ischemic damage to hepatocytes, such as cytoplasmic vacuolization, nuclear pyknosis, and disruption of the beam structure. The degree of damage increased with increasing ischemia time. Mason staining showed a moderate increase in connective tissue in the portal tracts and pericentral zones, indicating initial fibrotic changes. Ultramicroscopic examination (transmission electron microscopy) revealed swelling of mitochondria, disruption of the integrity of their cristae, expansion of the endoplasmic reticulum and formation of autophagosomes in hepatocytes. Oxygen consumption by liver tissue gradually decreased during the experiment, reaching 60-70% of the initial level by the end of the observation. Carbon dioxide production also decreased, but to a lesser extent, amounting to 75-85% of the baseline values. Analysis of the perfusate using a potentiostat-galvanostat IPS showed a gradual decrease in the oxidation-reduction potential, indicating an increase in hypoxia and depletion of antioxidant reserves. The activity of superoxide dismutase and catalase, key antioxidant enzymes, decreased by 30-40% and 20- 30%, respectively, compared with the initial values, indicating a weakening of the antioxidant defense. Conclusion. The obtained results indicate that the developed model using the Ex-Stream device is reproducible and allows for effective study of the state of ischemia-reperfusion injury. This opens up opportunities for conducting a larger and more comprehensive series of experiments, the results of which will be the subject of our further research.

• Book : 14(6)
• Pub. Date : 2025
• Page : pp.159-170
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• Pub. Date : 2025
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