Self-Heating Flower-like Nanoconstructs with Limited Incorporation of Yttrium in Maghemite: Effect of Chemical Composition on Heating Efficiency, Cytotoxicity and Genotoxicity.

Partial cation substitution can significantly change the physical properties of parent compounds. By controlling the chemical composition and knowing the mutual relationship between composition and physical properties, it is possible to tailor the properties of materials to those that are superior for desired technological application. Using the polyol synthesis procedure, a series of yttrium-substituted iron oxide nanoconstructs, γ-Fe2-xYxO3 (YIONs), was prepared. It was found that Y3+ could substitute Fe3+ in the crystal structures of maghemite (γ-Fe2O3) up to a limited concentration of ~1.5% (γ-Fe1.969Y0.031O3). Analysis of TEM micrographs showed that crystallites or particles were aggregated in flower-like structures with diameters from 53.7 ± 6.2 nm to 97.3 ± 37.0 nm, depending on yttrium concentration. To be investigated for potential applications as magnetic hyperthermia agents, YIONs were tested twice: their heating efficiency was tested and their toxicity was investigated. The Specific Absorption Rate (SAR) values were in the range of 32.6 W/g to 513 W/g and significantly decreased with increased yttrium concentration in the samples. Intrinsic loss power (ILP) for γ-Fe2O3 and γ-Fe1.995Y0.005O3 were ~8-9 nH·m2/Kg, which pointed to their excellent heating efficiency. IC50 values of investigated samples against cancer (HeLa) and normal (MRC-5) cells decreased with increased yttrium concentration and were higher than ~300 µg/mL. The samples of γ-Fe2-xYxO3 did not show a genotoxic effect. The results of toxicity studies show that YIONs are suitable for further in vitro/in vivo studies toward to their potential medical applications, while results of heat generation point to their potential use in magnetic hyperthermia cancer treatment or use as self-heating systems for other technological applications such as catalysis.

Circulating cytokine dynamics as potential biomarker of response to anti-PD-1 immunotherapy in BRAFwt MM patients.

BACKGROUND: The biomarkers of immune checkpoint inhibitors (ICIs) efficacy and safety are still urgently needed. As cytokines are easily detected and monitored in circulation, they could be used as potential predictors of response and immune-related adverse events (irAEs) for ICIs therapy. METHODS: The levels of TGF-ß, IFN-γ, IL-6, IL-8, IL-10 were measured in sera and plasma by ELISA method of 30 healthy controls (HC) and 32 BRAF wild type (wt) MM patients before and after every 12 weeks of Pembrolizumab, PD-1 inhibitor, until one year or disease progression (DP). RESULTS: Higher pretherapy levels of circulating TGF-ß, IFN-γ, IL-6, and IL-10 were shown in MM patients compared to HC. In patients with disease control, TGF-ß and IL-6 first decreased during the therapy, while then they started to successively increase reaching the initial values by the end of the follow up. Furthermore, in this group of patients IFN-γ increased, while IL-8 and IL-10 decreased at final points of the follow up. In patients with DP IL-6 increased at the time of progression, while IL-8 decreased when the best response was achieved. In patients with pseudoprogression IL-6 and IL-10 significantly increased compared to the pretreatment values. Melanoma patients with irAEs had increased baseline values of TGF-ß, IFN-γ, IL-6, and IL-10 compared to HC. However, no significant changes in cytokines levels were found in these patients during therapy. CONCLUSIONS: Inflammatory cytokines monitoring in circulation of BRAFwt MM patients could help in the selection of patients who will have the benefit from Pembrolizumab therapy.

Detection of humoral and cellular immune response to anti-SARS-CoV-2 BNT162b2 vaccine in breastfeeding women and naïve and previously infected individuals.

This study explored humoral and cellular responses to anti-SARS-CoV-2 BNT162b2 mRNA vaccine in breastfeeding women and naïve and seropositive individuals in the first six months after vaccination.Sixty-one volunteers vaccinated with two doses of the BNT162b2 mRNA vaccine were enrolled in the study. In-house developed ELISA was used for the quantification of SARS-CoV-2 RBD-specific antibodies. Cell surface marker expression and intracellular IFN-γ analysis were carried out by flow cytometry. The concentrations of IFN-γ, IL-6 and TNF were determined by ELISA. A significant rise in anti-RBD IgG antibody levels was observed 14 days after the first vaccine dose (p < 0.0001) in serum and milk. The expression of CD28 on CD4+ T cells was significantly higher compared to baseline (p < 0.05). There was a significant increase (p ≤ 0.05) in B cell lymphocyte subset after revaccination, and increased percentage of CD80+ B cells. The expression of IFN-γ in peripheral blood lymphocytes, CD3+ T cells and serum was significantly increased (p < 0.05). No significant difference in immune response was observed between breastfeeding women and other study participants. The anti-SARS-CoV-2 BNT162b2 mRNA vaccine-induced measurable and durable immune response in breastfeeding women and in naïve and previously infected individuals.

Correlation of Ionized Magnesium with the Parameters of Oxidative Stress as Potential Biomarkers in Patients with Anxiety and Depression: A Pilot Study.

Background: Magnesium (Mg) is the second most abundant intracellular cation. Ionized Mg is the only active form of Mg. The concentration of ionized Mg could be a potentially novel biomarker for anxiety and depression. Aim: The aim of this study was to assess the serum concentration of ionized Mg and its correlation with biomarkers of oxidative stress and inflammation in patients with anxiety and depression. Methods: In this study included 93 respondents were divided into 3 groups: C (control group-18 respondents); A (patients with anxiety disorder, dissociative/conversion disorders and somatoform disorders-36 patients); D (patients with depression-39 patients). Clinical diagnosis was based on ICD-10 criteria. Blood samples were used for standard laboratory analysis, ionized Mg analysis, oxidative stress, and inflammatory parameters. Results: Statistical significance was recorded between healthy volunteers and patients (anxiety/depression) in ionized Mg values. In anxious patients, malondialdehyde (MDA) had a positive correlation between the parameters of oxidative stress with ionized Mg. In depressive patients, MDA had a positive correlation, and glutathione peroxidase 1 (GPX1) a negative correlation with the concentration of ionized Mg. Conclusion: Ionized Mg and its correlation with parameters of oxidative stress could be potential biomarkers in anxious and depressive patients.