The aim of this study was to investigate miRNA profiles of clarified urine supernatant and combined urine vesicle fractions of healthy donors and patients with benign prostatic hyperplasia and prostate cancer (PCa). The comparative analysis of miRNA expression was conducted with a custom miRCURY LNA miRNA qPCR panel. Significant combinations of miRNA pairs were selected by the RandomForest-based feature selection algorithm Boruta; the difference of the medians between the groups and a 95% confidence interval was built using the bootstrap approach. The Asymptotic Wilcoxon-Mann-Whitney Test was performed for miRNA combinations to compare different groups of donors. Benjamini-Hochberg correction was used to adjust the statistical significance for multiple comparisons. The most diagnostically significant miRNAs pairs were miR-107-miR-26b.5p and miR-375.3p-miR-26b.5p in the urine supernatant fraction that discriminated the group of healthy patients and PCa patients, as well as miR-31.5p-miR-16.5p, miR-31.5p-miR-200b, miR-31.5p-miR-30e.3p and miR-31.5p-miR-660.5p in the fraction extracellular vesicles that were different between healthy men and benign prostate hyperplasia patients. Such statistical criteria as the occurrence of individual significant miRNA pairs in the total number of comparisons, median ΔCt difference, and confidence interval can be useful tools for determining reliable markers of PCa.
Intensive adjuvant radiotherapy (RT) is a standard treatment for glioblastoma multiforme (GBM) patients; however, its effect on the normal brain tissue remains unclear. Here, we investigated the short-term effects of multiple irradiation on the cellular and extracellular glycosylated components of normal brain tissue and their functional significance. Triple irradiation (7 Gy*3 days) of C57Bl/6 mouse brain inhibited the viability, proliferation and biosynthetic activity of normal glial cells, resulting in a fast brain-zone-dependent deregulation of the expression of proteoglycans (PGs) (decorin, biglycan, versican, brevican and CD44). Complex time-point-specific (24–72 h) changes in decorin and brevican protein and chondroitin sulfate (CS) and heparan sulfate (HS) content suggested deterioration of the PGs glycosylation in irradiated brain tissue, while the transcriptional activity of HS-biosynthetic system remained unchanged. The primary glial cultures and organotypic slices from triple-irradiated brain tissue were more susceptible to GBM U87 cells’ adhesion and proliferation in co-culture systems in vitro and ex vivo. In summary, multiple irradiation affects glycosylated components of normal brain extracellular matrix (ECM) through inhibition of the functional activity of normal glial cells. The changed content and pattern of PGs and GAGs in irradiated brain tissues are accompanied by the increased adhesion and proliferation of GBM cells, suggesting a novel molecular mechanism of negative side-effects of anti-GBM radiotherapy.
Recently, film materials based on the combination of noble metals have showed promising results for surface modification of medical implants, allowing both to improve biocompatibility and to acquire the increased antibacterial effect. An important challenge here is to combine the developed coating morphology, which is favorable for biological response, with a high protective function, which, on the contrary, requires a compact coating microstructure. In this work, we aimed to solve this problem with respect to the TiNi implant material. We have tested two types of compact thin sublayers: Iridium (Ir’), formed by metal-organic chemical vapor deposition (MOCVD), and gold (Au), formed by physical vapor deposition (PVD). Subsequently these sublayers were coated with a developed-columnar-iridium (Ir) by MOCVD. Features of the microstructure, chemical and phase composition of all these film materials were studied using powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The changes in the characteristics of TiNi martensitic transformation due to MOCVD experiments were also studied by differential scanning calorimetry (DSC). The biocompatibility of Ir’/TiNi, Au/TiNi, Ir/Ir’/TiNi, Ir/Au/TiNi samples was assessed by cytoxicity testing (Man-1 cells) and measuring of nickel content in the biological extracts. The application of both sublayers effectively reduces the release of nickel, which was previously shown for Ir/TiNi samples. This prevents the toxic effect. Note that the Ir’ sublayer better protects against nickel release, while the Au sublayer promotes cell proliferation.
This paper presents pioneering results on the evaluation of noble metal film hetero-structures to improve some functional characteristics of carbon-based implant materials: carbon-composite material (CCM) and carbon-fiber-reinforced polyetheretherketone (CFR-PEEK). Metal-organic chemical vapor deposition (MOCVD) was successfully applied to the deposition of Ir, Pt, and PtIr films on these carriers. A noble metal layer as thin as 1 µm provided clear X-ray imaging of 1–2.5 mm thick CFR-PEEK samples. The coated and pristine CCM and CFR-PEEK samples were further surface-modified with Au and Ag nanoparticles (NPs) through MOCVD and physical vapor deposition (PVD) processes, respectively. The composition and microstructural features, the NPs sizes, and surface concentrations were determined. In vitro biological studies included tests for cytotoxicity and antibacterial properties. A series of samples were selected for subcutaneous implantation in rats (up to 3 months) and histological studies. The bimetallic PtIr-based heterostructures showed no cytotoxicity in vitro, but were less biocompatible due to a dense two-layered fibrous capsule. AuNP heterostructures on CFR-PEEK promoted cell proliferation in vitro and exhibited a strong inhibition of bacterial growth (p < 0.05) and high in vitro biocompatibility, especially Au/Ir structures. AgNP heterostructures showed a more pronounced antibacterial effect, while their in vivo biocompatibility was better than that of the pristine CFR-PEEK, but worse than that of AuNP heterostructures.
Introduction: The choice of prosthesis for vertebral body reconstruction (VBR) remains a controversial issue due to the lack of a reliable solution. The subsidence rate of the most commonly used titanium mesh cages (TMC) ranges from 42.5% to 79.7%. This problem is primarily caused by the differences in the elastic modulus between the TMC and bone. This review aims to summarize the clinical and radiological outcomes of new 3D-printed artificial vertebral bodies (3DP AVB). Methods: A literature search of PubMed, Scopus and Google Scholar was conducted to extract relevant studies. After screening the titles and abstracts, a total of 50 articles were selected for full-text analysis. Results: Preliminary data suggest fewer implant-related complications with 3DP AVB. Most comparative studies indicate significantly lower subsidence rates, reduced operation times and decreased intraoperative blood loss. However, the scarcity of randomized clinical trials and the high variability of the results warrant caution. Conclusion: Most literature data show an advantage of 3DP AVB in terms of the operation time, intraoperative blood loss and subsidence rate. However, long manufacturing times, high costs and regulatory issues are this technology’s main drawbacks.
Cancer is the second leading cause of death worldwide behind cardiovascular diseases. Late stage of cancer at diagnosis and low efficacy of traditional cancer treatments result in low survival rate in cancer patients. Modern techniques to kill tumor cells are therefore needed. Over the last decade novel anticancer treatments have emerged from advances in our understanding of tumor cell biology, and a number of molecular and biologic targets have been identified. Chimeric antigen receptor T cell (CAR-T cell) therapy is a novel adoptive immunotherapy, which is used predominantly in the treatment of hematological malignancies. Moreover, it has been evidenced that cells of the innate immune system are key players at initiating and regulating adaptive immune responses. Studies focusing on innate immune cells for cancer immunotherapy show promising results. In this review, we describe functions of natural killer cells and analyze the rationale for using natural killer cells in cancer therapy.