Unfavorable prognoses and low survival rates are specific features of metastatic melanoma that justify the concern for the development of new therapeutic strategies. Lately, nanotechnology has become an attractive field of study due to recent advances in nanomedicine. Using a chick chorioallantoic membrane (CAM) implanted with xenografts harvested from C57BL/6 mice with B16F10 melanoma cells, we studied the effects of iron oxide nanoparticles functionalized with salicylic acid (SaMNPs) as a form of therapy on the local development of xenotransplants and CAM vessels. The SaMNPs induced an anti-angiogenic effect on the CAM vessels, which accumulated preferentially in the melanoma cells and induced apoptosis and extensive xenograft necrosis. As a result, this slowed the increase in the xenograft volume and reduced the melanoma cells’ ability to metastasize locally and distally. Further, we demonstrate the use of the chick CAM model as a tool for testing the action of newly synthesized nanocomposites on melanoma xenotransplants. The SaMNPs had a therapeutic effect on B16F10 melanoma due to the synergistic action of the two components of its structure: the coating of the salicylic acid with antiangiogenic and chemotherapeutic action and the core of iron oxides with cytotoxic action.

Melanoma is a melanocyte-derived skin cancer that has a high heterogeneity due to its phenotypic plasticity, a trait that may explain its ability to survive in the case of physical or molecular aggression and to develop resistance to therapy. Therefore, the therapy modulation of phenotypic switching in combination with other treatment modalities could become a common approach in any future therapeutic strategy. In this paper, we used the syngeneic model of B16F10 melanoma implanted in C57BL/6 mice to evaluate the phenotypic changes in melanoma induced by therapy with iron oxide nanoparticles functionalized with salicylic acid (SaIONs). The results of this study showed that the oral administration of the SaIONs aqueous dispersion was followed by phenotypic switching to highly pigmented cells in B16F10 melanoma through a cytotoxicity-induced cell selection mechanism. The hyperpigmentation of melanoma cells by the intra- or extracellular accumulation of melanic pigment deposits was another consequence of the SaIONs therapy. Additional studies are needed to assess the reversibility of SaIONs-induced phenotypic switching and the impact of tumor hyperpigmentation on B16F10 melanoma’s progression and metastasis abilities.

The liver is a key organ in the pharmacokinetics of iron oxide nanoparticles (IONPs). This paper examined how the intravenous (IV) or intragastric (IG) route of administration influenced the intrahepatic distribution or therapeutic effects of IONPs. Wistar rats, some with bleeding-induced anemia, and iron oxide nanoparticles functionalized with salicylic acid (SaIONPs), with an average hydrodynamic diameter of 73 nm, compatible with rat sinusoid fenestrations, were used in this study. Light microscopy and multispectral camera analysis of Prussian blue labeled SaIONPs allowed mapping of intrahepatic nanoparticle deposits and revealed intrahepatic distribution patterns specific to each route of administration: loading of Kupffer cells and periportal hepatocytes when the IV route was used and predominant loading of hepatocytes when the IG route was used. Reducing the time to return to baseline values for hemoglobin (HGB) in rats with bleeding-induced anemia with IV or IG therapy has proven the therapeutic potential of SaIONPs in such anemias. The long-term follow-up showed that IV therapy resulted in higher HGB values. Proper use of the administration routes may modulate intrahepatic distribution and therapeutic effects of nanoparticles. These results may be beneficial in theragnosis of liver disease.

The extracellular matrix (ECM) scaffolds are considered a gold standard for the engineering of appropriate grafts used in regenerative medicine for tissue repair, and decellularization of myocardial tissue is one of the most studied processes for obtaining natural ECM to date. Decellularization methods, agents used, or treatment durations can be varied to optimize cardiac tissue decellularization parameters. In this work we performed a morphological and morphometric analysis of cardiac tissue subjected to decellularization protocols based on Sodium Deoxycholate (SD) or Sodium Lauryl Sulfate (SLS) to identify factors that allow optimization of single-detergent based protocols for cardiac ECM manufacturing. For this, Wistar rat hearts (n=10) were subjected to 5 different decellularization protocols (n=2) and then histologically processed to achieve H&E or Azan trichrome stained sections for the morphological and morphometric analysis of the obtained ECM. The results of this study showed that SLS alters the spatial distribution of cardiac ECM collagen fibers, and SD can be successfully used in tailoring single-based detergent decellularization protocols by appropriately adjusting the application times of hypo/hyperosmotic shocks, which increases the lytic action of the detergent, and the washing times for the efficient elimination of cellular residues.

Whole-organ plastic resin casting is a very useful method for preserving rare pathological specimens for forensic/anatomical studies and for teaching/research purposes. Many techniques have been proposed over time, but most of them use special non-commercially available resin mixtures, lengthy protocols, and are overall not easily implemented in any anatomy/pathology department that might need such a procedure for rapid organ preservation. Here, we utilized anatomical sections of the human brain, heart, kidneys, spleen, large intestine, and lungs from on-display organs that were fixed for more than 1 year in 10% neutral-buffered formalin and from a freshly processed cadaver for teaching purposes in our Human Anatomy Department, and we optimized a fast-processing protocol without the use of any clearing agents, which yields solid, clear, cylindrical resin casting blocks. The resulting protocol, which takes no longer than 4 days, proves that at least three commonly used epoxy resins from hobby shops can be utilized without any restrictions, and the use of resin or glycerin vacuum-forced impregnation even offers two choices of intrinsic contrast, depending on the nature of the preparation. A number of innovations have been included here and compared to existing publications, such as the use of a system of permanent fixation plexiglas rods that maintain the organ in the desired position and become invisible in the final block, the use of UVC sterilization of the tissue to ensure a long shelf life of the block, and the utilization of cheap cylindrical polypropylene food containers as casting molds. Altogether, we present a simple resin-embedding protocol that can be made available to any department/institution without the need for expensive materials and specially trained personnel.

Knee osteoarthritis (KOA), one of the most common orthopedic disorders concerning the adult population worldwide, is a condition characterized by progressive destruction of the articular cartilage and the presence of an inflammatory process. The aim of our study was to assess whether nicotinamide riboside (NR), a popular anti-aging supplement, can reduce the rate of cartilage destruction and alleviate the inflammatory response compared to the commonly prescribed collagen supplement in a murine monoiodoacetate (MIA)-induced KOA model. Twenty Wistar rats were randomly assigned to 4 groups: sham (S), MIA and NR, MIA and hydrolyzed collagen (HC), and MIA. At the end of the experiment, the right knees and blood samples were collected for histological assessment and biochemical evaluation of nitric oxide, malondialdehyde, total antioxidant capacity, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, myeloperoxidase, and tumoral necrosis factor-alpha (TNF-α). The study determined that the treatment with NR in a similar dose with HC decreased blood/serum levels of oxidative stress biomarkers and the histological lesions in almost the same manner. The present findings suggest that NR may exhibit chondroprotective and anti-inflammatory effects in MIA-induced KOA in rats.