Toxicological research of novel nanomaterials is a major developmental step of their clinical approval. Since iron oxide magnetic nanoparticles have a great potential in cancer treatment and diagnostics, the investigation of their toxic properties is very topical. In this paper we synthesized bovine serum albumin‐coated iron oxide nanoparticles with different sizes and their polyethylene glycol derivative. To prove high biocompatibility of obtained nanoparticles the number of in vitro toxicological tests on human fibroblasts and U251 glioblastoma cells was performed. It was shown that albumin nanoparticles’ coating provides a stable and biocompatible shell and prevents cytotoxicity of magnetite core. On long exposure times (48 hours), cytotoxicity of iron oxide nanoparticles takes place due to free radical production, but this toxic effect may be neutralized by using polyethylene glycol modification.

Background: To evaluate the effectiveness of neuromuscular electrical stimulation (NMES) in early rehabilitation of patients with postoperative complications after cardiovascular surgery. Methods: 37 patients (25 men and 12 women) aged 45 to 70 years with postoperative complications after cardiovascular surgery were included in the study. Eighteen patients underwent NMES daily since postoperative day 3 until discharge in addition to standard rehabilitation program (NMES group), and 19 patients underwent standard rehabilitation program only (non-NMES group). The primary outcome was the knee extensors strength at discharge in NMES group and in control. Secondary outcomes were the handgrip strength, knee flexor strength, and cross-sectional area (CSA) of the quadriceps femoris in groups at discharge. Results: Baseline characteristics were not different between the groups. Knee extensors strength at discharge was significantly higher in the NMES group (28.1 [23.8; 36.2] kg on the right and 27.45 [22.3; 33.1] kg on the left) than in the non-NMES group (22.3 [20.1; 27.1] and 22.5 [20.1; 25.9] kg, respectively; P < .001). Handgrip strength, knee flexor strength, quadriceps CSA, and 6 minute walk distance at discharge in the groups had no significant difference. Conclusions: This pilot study shows a beneficial effect of NMES on muscle strength in patients with complications after cardiovascular surgery. The use of NMES showed no effect on strength of non-stimulated muscle, quadriceps CSA, and distance of 6-minute walk test at discharge. Further blind randomized controlled trials should be performed with emphasis on the effectiveness of NEMS in increasing muscle strength and structure in these patients.

The aim of the study were to evaluate the prognostic potential of serum level of N-terminal propeptide procollagen type III (PIIINP) and heart parameters for predicting heart cardiac fibrosis 1 year after ST-segment elevation myocardial infarction (STEMI) with preserved left ventricular ejection fraction (LVEF). 68 patients with STEMI and preserved LVEF with acute heart failure of the I-III degree according to the Killip classification were examined. Echocardiography was performed and PIIINP levels were measured on days 1 and 12, as well as 1 year after STEMI. A year after STEMI, was performed contrast magnetic resonance imaging and patients were assigned into four groups depending on the severity of cardiac fibrosis: cardiac fibrosis 0% (n=49, 57% of 86 patients); ≤5% (n=18, 20.9%); 6-15% (n=10, 11.6%); ≥16% (n=9, 10.5%). Direct correlations between the severity of cardiac fibrosis, PIIINP level and indicators of diastolic function were established. The risk of cardiac fibrosis increases at the level of PIIINP ≥381.4 ng / ml on the 12th day after STEMI with preserved LVEF (p=0.048). Thus, measuring the level of PIIINP in the inpatient period can allow timely identification of patients with a high risk of cardiac fibrosis 1 year after STEMI with preserved LVEF.

Evolution of SARS-CoV-2 in immunocompromised hosts may result in novel variants with changed properties, but the mode of selection underlying this process remains unclear. While escape from humoral immunity certainly plays a role in intra-host evolution, escape from cellular immunity is poorly understood. Here, we report a case of long-term COVID-19 in an immunocompromised patient with non-Hodgkin’s lymphoma who received treatment with rituximab and lacked neutralizing antibodies. Over the 318 days of the disease, the SARS-CoV-2 genome gained a total of 40 changes, 34 of which were present by the end of the study period. Among the acquired mutations, 12 reduced or prevented binding of known immunogenic SARS-CoV-2 HLA class I antigens, suggesting that virus immunoediting is largely driven by cytotoxic CD8 T cell clones. The two changes with the strongest effect, nsp3:T504A and nsp3:T504P, were experimentally assessed in a cytotoxic assay of the patient's CD8 T cells. Both these changes were associated with immune escape, with a stronger effect observed for nsp3:T504P, the change which ultimately got fixed. Together, these results suggest that CD8 T cell escape may be an underappreciated contributor to SARS-CoV-2 evolution in humans.

Regulation of neutrophil apoptosis plays a critical role in the inflammatory response. Inflammation has previously been shown to increase levels of extracellular β-nicotinamide adenine dinucleotide (NAD(+)). The present study demonstrates that extracellular NAD(+) at concentrations found in the inflamed tissues profoundly delays spontaneous apoptosis of human neutrophils as was evidenced by inhibition of phosphatidylserine (PS) exposure, DNA fragmentation and caspase-3 activation. The effect was abrogated by NF157, an antagonist of P2Y11 receptor, and was pertussis toxin-insensitive. The NAD(+)-mediated delay of neutrophil apoptosis was reversed by 2',5'-dideoxyadenosine, an inhibitor of adenylyl cyclase, and Rp-8-Br-cAMPS, an inhibitor of type I cAMP-dependent protein kinase A (PKA). Blocking of NAD(+)-induced influx of extracellular Ca(2+) with EGTA did not abolish the pro-survival effect of NAD(+). Extracellular NAD(+) inhibited proteasome-dependent degradation of Mcl-1 upstream of caspase activation and, furthermore, suppressed Bax translocation to the mitochondria and attenuated both dissipation of mitochondrial transmembrane potential (ΔΨm) and cytochrome c release from the mitochondria into the cytosol. Finally, we found that extracellular NAD(+) inhibited spontaneous activation of caspase-9, but not caspase-8, and the pro-survival effect of extracellular NAD(+) was abrogated by the inhibitor of caspase-9, but not by the inhibitor of caspase-8. Together, these results demonstrate that extracellular NAD(+) inhibits neutrophil apoptosis via P2Y11 receptor and cAMP/PKA pathway by regulating Mcl-1 level, Bax targeting to the mitochondria and mitochondrial apoptotic pathway. Thus, extracellular NAD(+) acts as a neutrophil survival factor that can contribute to prolonged neutrophil lifespan in inflammatory response.