Longitudinal Trend of Plasma Concentrations of Extracellular Vesicles in Patients Hospitalized for COVID-19

Plasma concentrations of extracellular vesicles (EVs) originating from cells involved in COVID-19-associated coagulopathy (CAC), their longitudinal trend and association with clinical outcomes were evaluated. Blood samples of consecutive COVID-19 patients admitted to a medical Unit were longitudinally collected within 48 h of admission, at discharge and 30 days post-discharge. EVs were analyzed using high sensitivity flow cytometry and phospholipid-dependent clotting time (PPL). The following EVs were measured: endothelium-, platelet-, leukocyte-derived, bearing tissue factor (TF)+, angiotensin-converting enzyme (ACE2)+, platelet-derived growth factor receptor-β (PDGF-β)+ and SARS-CoV-2-nucleoprotein (NP)+. 91 patients were recruited for baseline EV analysis (mean age 67 ± 14 years, 50.5% male) and 48 underwent the longitudinal evaluation. From baseline to 30-days post-discharge, we observed significantly decreased plasma concentrations of endothelium-derived EVs (E-Selectin+), endothelium-derived bearing TF (E-Selectin+ TF+), endothelium-derived bearing ACE2 (E-Selectin+ACE2+) and leukocyte-EVs bearing TF (CD45+TF+), p < 0.001, p = 0.03, p = 0.001, p = 0.001, respectively. Conversely, platelet-derived (P-Selectin+) and leukocyte-derived EVs (CD45+) increased from baseline to 30-days post-discharge (p = 0.038 and 0.032, respectively). EVs TF+, ACE2+, PDGF-β+, and SARS-CoV-2-NP+ did not significantly change during the monitoring. PPL increased from baseline to 30-days post-discharge (+ 6.3 s, p = 0.006). P-Selectin + EVs >1,054/µL were associated with thrombosis (p = 0.024), E-Selectin + EVs ≤531/µL with worsening/death (p 0.026) and 30-days P-Selectin+ and CD45 + EVs with persistent symptoms (p < 0.0001). We confirmed increased EVs originating from cells involved in CAC at admission and discharge. EVs derived from activated pericytes and expressing SARS-CoV-2-NP were also detected. 30-days post-discharge, endothelium-EVs decreased, while platelet- and leukocyte-EVs further increased, indicating that cellular activation persists long after the acute phase.

Platelet-Derived Growth Factor-BB Inhibits Intervertebral Disc Degeneration via Suppressing Pyroptosis and Activating the MAPK Signaling Pathway

Platelet-derived growth factor-BB (PDGF-BB) is a cytokine involved in tissue repair and tumor progression. It has been found to have expression differences between normal and degenerative intervertebral discs. However, it is not clear whether PDGF-BB has a protective effect on intervertebral disc degeneration (IDD). In this experiment, we treated nucleus pulposus cells (NPCs) with IL-1β to simulate an inflammatory environment and found that the extracellular matrix (ECM) anabolic function of NPCs in an inflammatory state was inhibited. Moreover, the induction of IL-1β also enhanced the expression of NLRP3 and the cleavage of caspase-1 and IL-1β, which activated the pyroptosis of NPCs. In this study, we studied the effect of PDGF-BB on IL-1β-treated NPCs and found that PDGF-BB not only significantly promotes the ECM anabolism of NPCs, but also inhibits the occurrence of pyroptosis and the production of pyroptosis products of NPCs. Consistent with this, when we used imatinib to block the PDGF-BB receptor, the above-mentioned protective effect disappeared. In addition, we found that PDGF-BB can also promote the ECM anabolism of NPCs by regulating the ERK, JNK, PI3K/AKT signaling pathways, but not the P38 signaling pathway. In vivo studies, mice that blocked PDGF-BB receptors showed more severe histological manifestations of intervertebral disc degeneration. In summary, our results indicate that PDGF-BB participates in inhibiting the occurrence and development of IDD by inhibiting pyroptosis and regulating the MAPK signaling pathway.

The effect of the geometry of the proximal anastomosis, markers of apoptosis and cell proliferation on the long-term patency following reconstructive interventions on the femoropopliteal arterial segment

Aim. To study changes in the topography of the orifice of the deep femoral artery (DFA), markers of proliferation, and apoptosis in patients after open interventions on the femoropopliteal arterial segment. Methods. The study included 35 patients with atherosclerotic peripheral arterial disease (PAD), femoral-popliteal occlusion, stage IIBIII of the disease according to the classification of A.V. PokrovskyFontaine, who underwent open surgery. The average age of the patients was 694.6 years. These patients included 26 men. Patients were divided into two groups: group A included 18 patients who underwent femoral-popliteal prosthetics (distal End-To-End bypass anastomoses), group B included 17 patients with femoral-popliteal bypass surgery (distal End-To-Side bypass anastomoses). The groups were comparable in terms of age and disease severity (p 0.05). Determination of serum platelet-derived growth factor BB (PDGF BB) and soluble form Fas (sFas) levels was carried out immediately before the intervention, on the 1st, 7th days, and 1 month after the operation. Duplex scanning (DS) was performed on day 7, after 1 and 18 months. Statistica 10.0 software was used for statistical data processing. The significance of differences between unrelated samples was assessed using the Student's t-test. The correlations between variables were analyzed by using Pearson's method. Results. On 1st day, there was a decrease in soluble Fas in patients of group A compared with group B (0.41 ng/ml vs 0.78 ng/ml, p=0.01). On the 7th day, the levels of serum platelet-derived growth factor BB were increased in patients of group A compared with group B (35.2 ng/ml vs 23.2 ng/ml, p=0.00001). After 1 month, the level of serum platelet-derived growth factor BB in patients of group A remained elevated compared with those in patients of group B (22.8 ng/ml vs 14.4 ng/ml, p=0.0003). Conclusion. Femoropopliteal prosthetics leads to a change in branching angle of the deep femoral artery up to 7080%, accompanied by changing dynamics of apoptotic markers and cell proliferation, leading to an increase in the thickness of neointimal hyperplasia and the progression of atherosclerosis.

Comparison between Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor Levels in Rhegmatogenous Retinal Detachment

Introduction. This study aimed to assess vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) levels within vitreous and blood serum samples of patients with rhegmatogenous retinal detachment (RRD) and their relationship to the development of proliferative vitreoretinopathy (PVR). Methods. Seventeen eyes of patients with RRD were included in the RRD group and divided into three subgroups: RRD without PVR, RRD with PVR grades A and B, and RRD with PVR grade C. Five control eyes (nucleus and intraocular lens drop) were included in this study. Blood serum and vitreous samples were collected during vitrectomy. VEGF-A and PDGF-AA levels were determined by enzyme-linked immunosorbent assay. Results. The mean vitreous VEGF-A level in the RRD group was 131.71 ± 58.25 pg/mL, and the mean vitreous PDGF-AA level was 174.62 ± 65.17 pg/mL. Both levels were significantly higher in the RRD group compared with the control group ( p < 0.05 ). Vitreous VEGF-A and PDGF-AA levels were the highest in RRD with PVR grade C subgroup, with mean levels of 179.87 ± 21.02 pg/mL and 229.44 ± 14.09 pg/mL, respectively ( p < 0.05 ). The vitreous VEGF-A/PDGF-AA ratios in the RRD subgroups were completely different. Conclusion. Based on the tendency of VEGF-A and PDGF-AA levels, RRD surgery has to be performed as soon as possible prior to retinal cell death and membrane proliferative formation.