👤 Stefania Bergamini

Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial tumors. Evidence suggests that these types of tumors may have high recurrence rates. In this context, the purinergic system, oxidative stress, and inflammation are important signaling pathways involved in the cancer's pathophysiology. This study aimed to evaluate the sociodemographic and diagnostic profiles, as well as assess the purinergic signaling, immunological, and redox profiles, of patients after PitNET resection. We collected sociodemographic data and the patients' diagnostic profiles. We also collected blood samples to analyze glycemia, triglycerides, albumin, and ATP levels. The ectonucleotidase activity was determined in peripheral blood mononuclear cells (PBMCs). In addition, we evaluated their redox and immunological profiles. There was a prevalence of gonadotropic macroadenoma derived from PIT-1 cells. We found that patients included in the PitNET group had increased glycemia, serum ATP levels, and ATP hydrolysis in PBMCs. Analyzing their immunological profiles, we found that patients had increased levels of IL-6, IL-10, and TNF, while the IL-27 level was decreased. Regarding their redox profiles, PitNET patients had increased levels of ROS and protein carbonylation. Unexpectedly, patients also showed increased levels of non-protein thiols (NPSHs), total thiols (PSHs), and ascorbic acid. Thus, the dysregulation of purinergic signaling sustained chronic inflammation and oxidative imbalance in PitNET patients for a long time after surgical resection. These data suggest that patients with PitNETs require long-term accompanying to prevent cancer recurrence prognosis. The biomarkers highlighted in this study may be good tools to help the medical approaches. Show less

The aim of this pilot study was to analyze the serum proteomic profile of women suffering from menstrual-related migraine (MM group, n = 15) and migraine in post-menopause (PM group, n = 15) in comparison with non-headache control females (C group, n = 15). Serum samples were subjected to two-dimensional gel electrophoresis (2-DE) followed by mass spectrometry (MS) analysis for protein identification. Based on 2D-gel maps and PDQuest 2-D software, 13 differentially expressed spots, corresponding to 12 unique proteins identified by Liquid Chromatography-Electrospray Ionization-Quadrupole-Time of Flight/tandem mass spectrometry (LC-ESI-QToF-MS/MS), were detected in the MM and PM groups vs C group. Five inflammatory and regulatory of vascular integrity proteins (prothrombin, serum amyloid P-component, Ig kappa chain C region, apolipoprotein A-I, serum amyloid A-4 protein) were found deregulated in both MM and PM groups compared to C group; MM group showed the upregulation of other inflammatory protein fragments (inter-alpha-trypsin inhibitor heavy chain H4 and complement C4-A) compared to C group; PM group, in comparison with C group, displayed a noteworthy upregulation of transthyretin and other deregulated proteins (tetranectin, alpha-1-antitrypsin, haptoglobin, apolipoprotein A-IV) playing a role in anti-inflammatory and reparative processes. In conclusion, proteomic analysis was able to reveal differences in protein expression between migraine sufferers and non-headache women; as in other neurological diseases characterized by neuroinflammation, the serum proteome of migraine women presents an abundance of proteins indicative of cellular damage, oxidative stress and inflammation. This relevant inflammatory status, if confirmed in larger series, could represent a target for menstrual-related migraine treatment. Show less

The aliphatic phosphine PTA (1,3,5-triaza-7-phosphaadamantane) is a promising ligand for metal complexes designed and developed as innovative inorganic drugs. In the present paper, an N-alkylated derivative of PTA, (PTAC16H33)X (X=I, C1, or X=PF6, C2) and its platinum coordination complex cis-[PtCl2(PTAC16H33)2](PF6)2, C3, were considered as components of cationic lipid nanoparticles (CLNs). Particularly, CLN1, CLN2 and CLN3 were obtained by adding derivatives C1, C2 or C3 during nanoparticles preparation, while CLN2-Pt were obtained by treating preformed CLN2 with Pt(II). It was demonstrated that CLN1, CLN2 and CLN3 can be produced with technological conventional methods. However, among the two here proposed protocols, the one based on the treatment of preformed nanoparticles appears more advantageous as compared to the other since it allows a quantitative association yield of Pt. As determined by ICP-OES, a content of P and Pt 2.2-fold and 2.5-fold higher in CLN2-Pt than in CLN3 was evidenced. For the first time was demonstrated that properly functionalized preformed nanoparticles can be efficiently used to obtain a post production Pt(II) complex while maintaining a cytotoxic activity toward cultured cells. In fact, the antiproliferative activity shown by CLN3, CLN2-Pt on the three model cancer cell lines was substantially similar and comparable to that of complex C3 in dmso solution. Thus N-alkylated-PTA derivatives in CLNs could be proposed as innovative biocompatible and water dispersible nanoparticles carrying lipophilic Pt complexes becoming an interesting and improved system with respect to dmso solution. Show less