Extracellular vesicles (EVs) are produced and released by all cells and are present in all body fluids. They exist in a variety of sizes, however, small extracellular vesicles (sEVs), the EV subset with a size range from 30 to 150 nm, are of current interest. They are characterized by a distinct biogenesis and complex cargo composition, which reflects the cytosolic contents and cell-surface molecules of the parent cells. This cargo consists of proteins, nucleic acids, and lipids and is competent in inducing signaling cascades in recipient cells after surface interactions or in initiating the generation of a functional protein by delivering nucleic acids. Based on these characteristics, sEVs are now considered as important mediators of intercellular communication. One hallmark of sEVs is the promotion of angiogenesis. It was shown that sEVs interact with endothelial cells (ECs) and promote an angiogenic phenotype, ultimately leading to increased vascularization of solid tumors and disease progression. It was also shown that sEVs reprogram cells in the tumor microenvironment (TME) and act in a functionally cooperative fashion to promote angiogenesis by a paracrine mechanism involving the differential expression and secretion of angiogenic factors from other cell types. In this review, we will focus on the distinct functions of tumor-cell-derived sEVs (TEX) in promotion of angiogenesis and describe their potential as a therapeutic target for anti-angiogenic therapies. Also, we will focus on non-cancer stroma-cell-derived small extracellular vesicles and their potential role in stimulating a pro-angiogenic TME.

Natural compounds, such as resveratrol (Res), are currently used as adjuvants for anticancer therapies. To evaluate the effectiveness of Res for the treatment of ovarian cancer (OC), we screened the response of various OC cell lines to the combined treatment with cisplatin (CisPt) and Res. We identified A2780 cells as the most synergistically responding, thus optimal for further analysis. Because hypoxia is the hallmark of the solid tumor microenvironment, we compared the effects of Res alone and in combination with CisPt in hypoxia (pO₂ = 1%) vs. normoxia (pO₂ = 19%). Hypoxia caused an increase (43.2 vs. 5.0%) in apoptosis and necrosis (14.2 vs. 2.5%), reactive oxygen species production, pro-angiogenic HIF-1α (hypoxia-inducible factor-1α) and VEGF (vascular endothelial growth factor), cell migration, and downregulated the expression of ZO1 (zonula occludens-1) protein in comparison to normoxia. Res was not cytotoxic under hypoxia in contrast to normoxia. In normoxia, Res alone or CisPt+Res caused apoptosis via caspase-3 cleavage and BAX, while in hypoxia, it reduced the accumulation of A2780 cells in the G2/M phase. CisPt+Res increased levels of vimentin under normoxia and upregulated SNAI1 expression under hypoxia. Thus, various effects of Res or CisPt+Res on A2780 cells observed in normoxia are eliminated or diminished in hypoxia. These findings indicate the limitations in using Res as an adjuvant with CisPt therapy in OC.

Mortality in COVID-19 is mainly associated with respiratory failure, cytokine storm, and macrophage activation. Oxygenation and anti-inflammatory effects of Hyperbaric Oxygen Therapy (HBOT) suggest that it is a promising adjunct treatment for COVID-19. Repeated sessions of HBO with standard COVID-19 therapy were used to reduce the inflammation and increase oxygenation. We evaluated the safety and efficacy of HBOT in avoiding the replacement ventilation and/or ECMO and its effect on the inflammatory process. Twenty-eight moderate-to-severe COVID-19 patients were randomized into control or HBOT group. HBOT patients participated in 5 hyperbaric sessions (60 min). Before and after each session blood gas levels and vital parameters were monitored. Blood samples were collected for extended biochemical tests, blood morphology and immunological assays. There were 3 deaths in the control, no deaths in the HBOT group. No adverse events leading to discontinuation of HBOT were observed and patients receiving HBOT required lower oxygen delivery. We observed decrease in CRP, ferritin and LDH and increase in CD3 in HBOT group compared to control. This study confirmed the feasibility and safety of HBOT in patients with COVID-19 and indicated HBOT can lead to alleviation of inflammation and partial restoration of T cell responses.

Tissue hypoxia is commonly observed in head and neck squamous cell carcinomas (HNSCCs), resulting in molecular and functional alterations of the tumor cells. The aim of this study was to characterize tumor-derived small extracellular vesicles (sEVs) released under hypoxic vs. normoxic conditions and analyze their proteomic content. HNSCC cells (FaDu, PCI-30, SCC-25) and HaCaT keratinocytes were cultured in 21, 10, 5, and 1% O₂. sEVs were isolated from supernatants using size exclusion chromatography (SEC) and characterized by nanoparticle tracking analysis, electron microscopy, immunoblotting, and high-resolution mass spectrometry. Isolated sEVs ranged in size from 125–135 nm and contained CD63 and CD9 but not Grp94. sEVs reflected the hypoxic profile of HNSCC parent cells: about 15% of the total detected proteins were unique for hypoxic cells. Hypoxic sEVs expressed a common signature of seven hypoxia-related proteins (KT33B, DYSF, STON2, MLX, LIPA3, NEK5, P12L1) and were enriched in pro-angiogenic proteins. Protein profiles of sEVs reflected the degree of tumor hypoxia and could serve as potential sEV-based biomarkers for hypoxic conditions. Adaptation of HNSCC cells to hypoxia is associated with increased release of sEVs, which are enriched in a unique protein profile. Thus, tumor-derived sEVs can potentially be useful for evaluating levels of hypoxia in HNSCC.

Introduction: Hyperbaric oxygen therapy (HBOT) is one of the treatment methods in patients with sudden sensorineural hearing loss (SSNHL). It is recommended as an elective treatment in patients undergoing steroid therapy. According to current scientific reports, HBOT should be implemented within two weeks after the first symptoms. However, as far as the profile of HBOT is concerned, there are no straightforward recommendations. Methods: The data obtained from the medical records of 218 patients undergoing HBOT for SSNHL at the Military Institute of Medicine—National Research Institute were analyzed statistically for the impact of the duration and the delay in implementing HBOT on the end results of pure-tone audiometry (PTA). Results: A statistically significant hearing improvement in patients undergoing more than 15 cycles of HBOT was detected at all frequencies except for 1500 Hz; in the group reporting for treatment with a delay of more than 10 days, hearing improvement was statistically unsignificant at frequencies of 1500, 3000, and 4000 Hz. Conclusions: The statistical analysis showed that the urgent onset of HBOT could be a significant factor in the therapy of SSNHL.

In the course of atopic dermatitis (AD), the overactivity of the immune system, associated with predominant Th2 lymphocyte responses, is observed, which leads to an increased inflammatory reaction. Cases of a severe course of atopic dermatitis lead to the search for new therapeutic options. The aim of this study was to assess the effects of hyperbaric oxygen therapy (HBOT) treatment for severe cases of AD in children. A total of 15 children with severe AD underwent therapy. The influence of HBOT on the clinical course of AD and immunomodulatory effect of the therapy was analyzed by the SCORAD and objective SCORAD (oSCORAD) scales and by determining the serum concentration of immunological parameters (blood: nTreg lymphocytes, CD4+CD25highCD127-FOXP3+, NKT lymphocytes CD3+, CD16/56+, and serum: total IgE, cytokines IL-4, IL-6, and IL-10, before and after the 30-day treatment cycle). The study showed a significant effect of the therapy on the improvement of the skin condition. In all children, a reduction in the extent and intensity of skin lesions, reduction of redness, swelling, oozing/crusting, scratch marks and skin lichenification after HBOT was observed. Patients also reported a reduction in the intensity of pruritus and an improvement in sleep quality after therapy. In all children, a statistically significant decrease in the serum level of IgE was observed. However, no statistically significant changes in the blood levels of IL-4, IL-6 and IL-10, as well as the percentage of CD4⁺CD25^highCD127⁻FOXP3⁺ Treg and NKT lymphocytes, were found. In conclusion, the use of hyperbaric therapy has a positive impact on treatment results in children with a severe course of atopic dermatitis.