Oocyte–cumulus cell interaction is essential for oocyte maturation and competence. The bidirectional crosstalk network mediated by gap junctions is fundamental for the metabolic cooperation between these cells. As cumulus cells exhibit a more glycolytic phenotype, they can provide metabolic substrates that the oocyte can use to produce ATP via oxidative phosphorylation. The impairment of mitochondrial activity plays a crucial role in ovarian aging and, thus, in fertility, determining the success or failure of assisted reproductive techniques. This review aims to deepen the knowledge about the electro-metabolic coupling of the cumulus–oocyte complex and to hypothesize a putative role of potassium channel modulators in order to improve fertility, promote intracellular Ca²⁺ influx, and increase the mitochondrial biogenesis and resulting ATP levels in cumulus cells.

Resveratrol attracts great interest because of the plethora of in vitro effects at the micromolar concentration range. Unfortunately, these effects are difficult to establish in vivo, due to the low concentration of resveratrol reached. This discrepancy is due to the molecules low solubility in water that favors the propensity for an intestinal absorption rather than in the gastric compartment. To address these challenges, we developed a Solid Dispersion of Resveratrol Supported by Magnesium Di Hydroxide formulation (Resv@MDH). This formulation displays increased water solubility and better bioavailability relative to pure resveratrol in the rabbit animal model. In our study, we evaluated the pharmacokinetics profile of resveratrol in six healthy human subjects following 180 mg of oral resveratrol administration, derived from Resv@MDH or pure resveratrol. Free resveratrol was evaluated in the whole blood sample by using HPLC - MS/MS. In comparison with pure resveratrol that displays an increase of the maximum plasma concentration, Cmax at about 90 min and 2 μM, Resv@MDH displays an earlier peak of resveratrol concentration with an increase of Cmax at about 30 min and 6 μM. The different kinetics suggest a main gastric route for resveratrol absorption from Resv@MDH, where, because of its improved dissolution rate, there seems to be a higher propensity for an acidic environment, as opposed to that with pure resveratrol. This conclusion is also supported by the numerical simulation analysis, which considers the principal steps during the oral route administration. Moreover, there is a 2-fold increase in the amount of free resveratrol with respect to pure resveratrol confirming a better bioavailability observed in the animal model. The characteristic feature of the pharmacokinetic profile of Resv@MDH implies that the beneficial properties of resveratrol in human health should be capitalized on it.

The synthesis of ultrasmall UiO-66 nanoparticles (NPs) with an average size of 25 nm, determined by X-ray powder diffraction and electron microscopies analysis, is reported. The NPs were stabilized in water by dialyzing the NP from the DMF used for the synthesis. DLS measurements confirmed the presence of particles of 100 nm, which are spherical aggregates of smaller particles of 20–30 nm size. The NP have a BET surface area of 700 m²/g with an external surface area of 300 m²/g. UiO-66_N (UiO-66 nanoparticles) were loaded with acridine orange as fluorescent probe. UV-vis spectroscopy analysis revealed no acridine loss after 48 h of agitation in simulated body fluid. The biocompatibility of UiO-66_N was evaluated in human glioblastoma (GBM) cell line U251, the most malignant (IV grade of WHO classification) among brain tumors. In U251 cells, UiO-66_N are inert since they do not alter the cell cycle, the viability, migration properties, and the expression of kinases involved in cancer cell growth. The internalization process was evident after a few hours of incubation. After 24 h, UiO-66_N@Acr (UiO-66_N loaded with acridine orange) were detectable around the nuclei of the cells. These data suggest that small UiO-66 are biocompatible NP and could represent a potential carrier for drug delivery in glioblastoma therapies.

Background: Chronic lymphocytic leukemia (CLL) is an incurable disorder associated with alterations in several pathways essential for survival and proliferation. Despite the advances made in CLL therapy with the new target agents, in some cases, relapses and resistance could occur, making the discovery of new alternatives to manage CLL refractoriness necessary. To provide new therapeutic strategies for CLL, we investigated the anti-leukemic activity of silver nanoparticles (AgNPs), whose impact on CLL cells has been poorly explored. Methods: We studied the action mechanisms of AgNPs in vitro through flow cytometry and molecular analyses. To improve the bioavailability of AgNPs, we generated AgNPs coated with the anti-CD20 antibody Rituximab (AgNPs@Rituximab) and carried out imaging-based approaches and in vivo experiments to evaluate specificity, drug uptake, and efficacy. Results: AgNPs reduced the viability of primary CLL cells and the HG-3 cell line by inducing an intrinsic apoptotic pathway characterized by Bax/Bcl-2 imbalance, caspase activation, and PARP degradation. Early apoptotic events triggered by AgNPs included enhanced Ca²⁺ influx and ROS overproduction. AgNPs synergistically potentiated the cytotoxicity of Venetoclax, Ibrutinib, and Bepridil. In vitro, the AgNPs@Rituximab conjugates were rapidly internalized within CLL cells and strongly prolonged the survival of CLL xenograft models compared to each unconjugated single agent. Conclusions: AgNPs showed strong anti-leukemic activity in CLL, with the potential for clinical translation in combination with agents used in CLL. The increased specificity of AgNPs@Rituximab toward CLL cells could be relevant for overcoming in vivo AgNPs’ non-specific distribution and increasing their efficacy.

Human glioblastoma is probably the most malignant and aggressive among cerebral tumors, of which it represents approximately 80% of the reported cases, with an overall survival rate that is quite low. Current therapies include surgery, chemotherapy, and radiotherapy, with associated consistent side effects and low efficacy. The hardness in reaching the site of action, and overcoming the blood–brain barrier, is a major limitation of pharmacological treatments. In this paper, we report the synthesis and characterization of ZIF-90 (ZIF, Zeolitic Imidazolate Framework) nanoparticles as putative carriers of anticancer drugs to the brain. In particular, we successfully evaluated the biocompatibility of these nanoparticles, their stability in body fluids, and their ability to uptake in U251 human glioblastoma cell lines. Furthermore, we managed to synthesize ZIF-90 particles loaded with berberine, an alkaloid reported as a possible effective adjuvant in the treatment of glioblastoma. These findings could suggest ZIF-90 as a possible new strategy for brain cancer therapy and to study the physiological processes present in the central nervous system.

Glioblastoma is one the most aggressive primary brain tumors in adults, and, despite the fact that radiation and chemotherapy after surgical approaches have been the treatments increasing the survival rates, the prognosis of patients remains poor. Today, the attention is focused on highlighting complementary treatments that can be helpful in improving the classic therapeutic approaches. It is known that 1α,25(OH)₂ vitamin D₃, a molecule involved in bone metabolism, has many serendipidy effects in cells. It targets normal and cancer cells via genomic pathway by vitamin D3 receptor or via non-genomic pathways. To interrogate possible functions of 1α,25(OH)₂ vitamin D3 in multiforme glioblastoma, we used three cell lines, wild-type p53 GL15 and mutant p53 U251 and LN18 cells. We demonstrated that 1α,25(OH)₂ vitamin D3 acts via vitamin D receptor in GL15 cells and via neutral sphingomyelinase1, with an enrichment of ceramide pool, in U251 and LN18 cells. Changes in sphingomyelin/ceramide content were considered to be possibly responsible for the differentiating and antiproliferative effect of 1α,25(OH)₂ vitamin D in U251 and LN18 cells, as shown, respectively, in vitro by immunofluorescence and in vivo by experiments of xenotransplantation in eggs. This is the first time 1α,25(OH)₂ vitamin D3 is interrogated for the response of multiforme glioblastoma cells in dependence on the p53 mutation, and the results define neutral sphingomyelinase1 as a signaling effector.