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In genetically heterogeneous mice produced by the CByB6F1 x C3D2F1 cross, the "non-feminizing" estrogen, 17-α-estradiol (17aE2), extended median male lifespan by 19% (p

The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.

Canagliflozin (Cana) is an FDA-approved diabetes drug that protects against cardiovascular and kidney diseases. It also inhibits the sodium glucose transporter 2 by blocking renal reuptake and intestinal absorption of glucose. In the context of the mouse Interventions Testing Program, genetically heterogeneous mice were given chow containing Cana at 180 ppm at 7 months of age until their death. Cana extended median survival of male mice by 14%. Cana also increased by 9% the age for 90th percentile survival, with parallel effects seen at each of 3 test sites. Neither the distribution of inferred cause of death nor incidental pathology findings at end-of-life necropsies were altered by Cana. Moreover, although no life span benefits were seen in female mice, Cana led to lower fasting glucose and improved glucose tolerance in both sexes, diminishing fat mass in females only. Therefore, the life span benefit of Cana is likely to reflect blunting of peak glucose levels, because similar longevity effects are seen in male mice given acarbose, a diabetes drug that blocks glucose surges through a distinct mechanism, i.e., slowing breakdown of carbohydrate in the intestine. Interventions that control daily peak glucose levels deserve attention as possible preventive medicines to protect from a wide range of late-life neoplastic and degenerative diseases.

Abstract Background Mesenchymal stromal cells (MSCs) have an inherent migratory capacity towards tumor tissue in vivo. With the future objective to quantify the tumor homing efficacy of MSCs, as first step in this direction we investigated the use of inorganic nanoparticles (NPs), in particular ca. 4 nm-sized Au NPs, for MSC labeling. Time dependent uptake efficiencies of NPs at different exposure concentrations and times were determined via inductively coupled plasma mass spectrometry (ICP-MS). Results The labeling efficiency of the MSCs was determined in terms of the amount of exocytosed NPs versus the amount of initially endocytosed NPs, demonstrating that at high concentrations the internalized Au NPs were exocytosed over time, leading to continuous exhaustion. While exposure to NPs did not significantly impair cell viability or expression of surface markers, even at high dose levels, MSCs were significantly affected in their proliferation and migration potential. These results demonstrate that proliferation or migration assays are more suitable to evaluate whether labeling of MSCs with certain amounts of NPs exerts distress on cells. However, despite optimized conditions the labeling efficiency varied considerably in MSC lots from different donors, indicating cell specific loading capacities for NPs. Finally, we determined the detection limits of Au NP-labeled MSCs within murine tissue employing ICP-MS and demonstrate the distribution and homing of NP labeled MSCs in vivo. Conclusion Although large amounts of NPs improve contrast for imaging, duration and extend of labeling needs to be adjusted carefully to avoid functional deficits in MSCs. We established an optimized labeling strategy for human MSCs with Au NPs that preserves their migratory capacity in vivo.

Aim. The main aim of our research is to evaluate the process of rat lung decellularization and recellularization as the initial step of tissue-engineered organs creation.Materials and methods. Rat lung decellularization was performed by perfusion with detergents and enzymes with concomitant atmospheric air ventilation through the trachea. The quality of decellularization was analyzed with routine histological and immunohistochemical staining techniques, DNA content was determined quantitatively by spectrophotometer. For static and whole organ reseeding as a model of cells’ behavior mesenchymal multipotent stromal cells were used. Recellularization was followed by assessment of the cellular metabolic activity by colorimetric method; cell viability was analyzed by calcein and ethidium homodimer staining. Matrix qualitative evaluation after recellularization was performed using immunohistochemical staining methods.Results. 92% of allogeneic DNA was eliminated after decellularization. Histological staining revealed no residual cells and cell nuclei; preservation of the fibers of extracellular matrix was confirmed by immunohistochemical staining for laminin, elastin, fibronectin, collagen types I and IV before and after decellularization. The scaffold does not exhibit toxic properties after reseeding; cell viability and metabolic activity were proved after cultivation.Conclusion. The experience of rat lung decellularization and recellularization can be the prospective basis for protocols of organ recellularization and tissue engineered lungs creation.

Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in a diverse range of biological processes. For future therapeutic applications and for EV biology research in general, understanding the in vivo fate of EVs is of utmost importance. Here we studied biodistribution of EVs in mice after systemic delivery. EVs were isolated from 3 different mouse cell sources, including dendritic cells (DCs) derived from bone marrow, and labelled with a near-infrared lipophilic dye. Xenotransplantation of EVs was further carried out for cross-species comparison. The reliability of the labelling technique was confirmed by sucrose gradient fractionation, organ perfusion and further supported by immunohistochemical staining using CD63-EGFP probed vesicles. While vesicles accumulated mainly in liver, spleen, gastrointestinal tract and lungs, differences related to EV cell origin were detected. EVs accumulated in the tumour tissue of tumour-bearing mice and, after introduction of the rabies virus glycoprotein-targeting moiety, they were found more readily in acetylcholine-receptor-rich organs. In addition, the route of administration and the dose of injected EVs influenced the biodistribution pattern. This is the first extensive biodistribution investigation of EVs comparing the impact of several different variables, the results of which have implications for the design and feasibility of therapeutic studies using EVs.

The study presents data about structural interaction between decellularizedrat heart matrix and stem cells used for recellularization. The effect of decellularized scaffold influence on the potential cells ability for differentiation without growth factors was evaluated. Morphological analysis of recellularized rat heart matrix was conducted. Rat heart scaffold influence on the proliferative cells capacity during recellularization process was assessed by immunohistochemical analysis. Cell viability on the scaffold was determined by the colorimetric test with MTT-reagent.

study started an investigation into the archeology of the largest construction sites that concerned the monastery. Given the limited availability of archival documents, the research was based both on the interpretation of the survey of the construction and the direct analysis of the artifact. Providing specific dating was not the aim pursued; in fact it was to highlight the constructive relations between some key interventions, which were not known until now or whose importance was not fully understood. In particular, the monastery and the remains of the original crypt, incorporated and re-used under the presbytery of the church, have been taken into account. Great changes have been identified in the East Wing of the monastery, where the original nucleus was formed by a first part of the bell tower and an adjacent room on the ground floor. In the west wing, besides highlighting many additions, a large space was brought to light covered by tympanum arches, which had been forgotten and was probably used as a refectory.