Castration-resistant prostate cancer (CRPC) is a common form of prostate cancer in which docetaxel-based chemotherapy is used as the first line. The present study is devoted to the analysis of transcriptome profiles of tumor cells in the development of resistance to docetaxel as well as to the assessment of the combined effect with the XAV939 tankyrase inhibitor on maintaining the sensitivity of tumor cells to chemotherapy. RNA-Seq was performed for experimental PC3 cell lines as well as for plasma exosome samples from patients with CRPC. We have identified key biological processes and identified a signature based on the expression of 17 mRNA isoforms associated with the development of docetaxel resistance in PC3 cells. Transcripts were found in exosome samples, the increased expression of which was associated with the onset of progression of CRPC during therapy. The suppression of pathways associated with the participation of cellular microtubules has also been shown when cells are treated with docetaxel in the presence of XAV939. These results highlight the importance of further research into XAV939 as a therapeutic agent in the treatment of CRPC; moreover, we have proposed a number of mRNA isoforms with high predictive potential, which can be considered as promising markers of response to docetaxel.

One of the severe complications occurring because of the patient’s intubation is tracheal stenosis. Its incidence has significantly risen because of the COVID-19 pandemic and tends only to increase. Here, we propose an alternative to the donor trachea and synthetic prostheses—the tracheal equivalent. To form it, we applied the donor trachea samples, which were decellularized, cross-linked, and treated with laser to make wells on their surface, and inoculated them with human gingiva-derived mesenchymal stromal cells. The fabricated construct was assessed in vivo using nude (immunodeficient), immunosuppressed, and normal mice and rabbits. In comparison with the matrix ones, the tracheal equivalent samples demonstrated the thinning of the capsule, the significant vessel ingrowth into surrounding tissues, and the increase in the submucosa resorption. The developed construct was shown to be highly biocompatible and efficient in trachea restoration. These results can facilitate its clinical translation and be a base to design clinical trials. Graphical Abstract

Among all of the materials used in tissue engineering in order to develop bioequivalents, collagen shows to be the most promising due to its superb biocompatibility and biodegradability, thus becoming one of the most widely used materials for scaffold production. However, current imaging techniques of the cells within collagen scaffolds have several limitations, which lead to an urgent need for novel methods of visualization. In this work, we have obtained groups of collagen scaffolds and selected the contrasting agents in order to study pores and patterns of cell growth in a non-disruptive manner via X-ray computed microtomography (micro-CT). After the comparison of multiple contrast agents, a 3% aqueous phosphotungstic acid solution in distilled water was identified as the most effective amongst the media, requiring 24 h of incubation. The differences in intensity values between collagen fibers, pores, and masses of cells allow for the accurate segmentation needed for further analysis. Moreover, the presented protocol allows visualization of porous collagen scaffolds under aqueous conditions, which is crucial for the multimodal study of the native structure of samples.

Purpose: The intracranial three-dimensional (3D) visualization of the whole volume of the eyeball at micrometric resolution has not been achieved yet either in clinical nor in preclinical diagnostic research. Overcoming this limitation may provide a new tool for clinical and preclinical studies of different pathologies of the various sections of the eye. The aim of this work is to give the first insight of a volumetric visualization at the high resolution of the entire enucleated and intracranial postmortem rabbit eyeballs. Methods: X-ray computed tomography phase-contrast imaging was used to obtain 3D models of enucleated and intracranial rabbit eyes. Images were compared with the ones measured by using optical coherence tomography (OCT) images. The experiment was carried out at the European Synchrotron Radiation Facility. Results: Combining the unique possibilities offered by phase-contrast imaging, microtomography, and the properties of synchrotron radiation, the 3D visualization of the whole eyeball, at an isotropic voxel size of 3.1 μm³, is reported here for the first time. Conclusions: High image contrast is achieved without the necessity of injection of contrast agents, thanks to the superior performances, achieved by x-ray phase-contrast imaging with respect to the conventional radiographic imaging. The measurement protocol developed within this work opens the way for in vivo high-resolution visualization of the entire organ.