Glioblastoma (GBM) is the most malignant and lethal brain tumor. Current standard treatment consists of surgery followed by radiotherapy/chemotherapy; however, this is only a palliative approach with a mean post-operative survival of scarcely ~12–15 months. Thus, the identification of novel therapeutic targets to treat this devastating pathology is urgently needed. In this context, the truncated splicing variant of the somatostatin receptor subtype 5 (sst5TMD4), which is produced by aberrant alternative splicing, has been demonstrated to be overexpressed and associated with increased aggressiveness features in several tumors. However, the presence, functional role, and associated molecular mechanisms of sst5TMD4 in GBM have not been yet explored. Therefore, we performed a comprehensive analysis to characterize the expression and pathophysiological role of sst5TMD4 in human GBM. sst5TMD4 was significantly overexpressed (at mRNA and protein levels) in human GBM tissue compared to non-tumor (control) brain tissue. Remarkably, sst5TMD4 expression was significantly associated with poor overall survival and recurrent tumors in GBM patients. Moreover, in vitro sst5TMD4 overexpression (by specific plasmid) increased, whereas sst5TMD4 silencing (by specific siRNA) decreased, key malignant features (i.e., proliferation and migration capacity) of GBM cells (U-87 MG/U-118 MG models). Furthermore, sst5TMD4 overexpression in GBM cells altered the activity of multiple key signaling pathways associated with tumor aggressiveness/progression (AKT/JAK-STAT/NF-κB/TGF-β), and its silencing sensitized GBM cells to the antitumor effect of pasireotide (a somatostatin analog). Altogether, these results demonstrate that sst5TMD4 is overexpressed and associated with enhanced malignancy features in human GBMs and reveal its potential utility as a novel diagnostic/prognostic biomarker and putative therapeutic target in GBMs.

Prostate cancer (PCa) is the tumour pathology with the second highest incidence among men worldwide. PCa is strongly influenced by obesity (OB), which increases its aggressiveness. Hence, some metabolic drugs like metformin have emerged as potential anti-tumour agents against several endocrine-related cancers. Likewise, a high adherence to the Mediterranean diet has been associated with lower rates of OB and a reduction in PCa aggressiveness since this diet contains phenolic bioactive compounds such as hydroxytyrosol (HT) that is mainly present in extra virgin olive oil. Thus, we decided to analyse the therapeutic potential of the combination of HT + metformin in different PCa cell models. Specifically, combinations of different doses of HT and metformin were evaluated by analysing the proliferation rate of LNCaP, 22Rv1, DU-145, and PC−3 cells using the SynergicFinder method. The results revealed a synergistic effect of HT + metformin in significantly reducing proliferation, especially in LNCaP cells. This anti-tumour effect of HT + metformin was also confirmed in migration and tumoursphere formation assays in LNCaP. The effects on the cell cycle and apoptosis were also assessed by flow-cytometry, and a cycle arrest in the G1 phase and an increase in late apoptosis were observed with the combination of HT + metformin. The phosphorylation levels of critical components of different oncogenic pathways were measured which revealed that the combination of HT + metformin significantly reduced the activity of multiple components of the MAPK, AKT, and TGF-β pathways. Overall, the combination of HT + metformin might represent a new therapeutic avenue for the management of PCa patients, an observation that certainly warrants further investigation through a well-designed clinical trial.

Yeast biocapsules are a novel immobilization technology that could be used in fermentation processes. They are spherical structures consisting of yeast cells encapsulated and attached to the hyphae of a filamentous fungus. Yeast biocapsules offer a cutting-edge approach to cell immobilization, with significant potential for advancing fermented food production. By enhancing fermentation control, improving product quality, and increasing process efficiency, these biocapsules represent a key innovation in food fermentation technology, particularly in the production of alcoholic beverages such as beer and wine. Proteomic analysis of two-dimensional gels was carried out to study changes in proteins expressed in (i) co-immobilized yeast cells, and (ii) free-format yeast cells. This analysis showed that the proteins expressed in co-immobilized yeast cells played critical roles in DNA repair, cell cycle regulation, protein synthesis, and translation, whereas the proteins expressed by free yeast cells were mainly related to glycolysis. These findings suggest a defense response of the co-immobilized yeast against fungal interactions, involving regulatory mechanisms at the DNA, RNA, and protein levels. This study opens new avenues for exploring yeast–fungus co-immobilization, including stress responses, the nature of the binding polymers, and the proteomics of biocapsules. Additionally, investigating natural co-immobilization mechanisms between various microorganisms could uncover further biotechnological applications and biocatalytic activities.

This study investigates nitrogen metabolism during the middle of the second fermentation in stopped bottles of sparkling wine, focusing on two flor Saccharomyces cerevisiae yeast strains (G1 and N62) isolated from the velum of biologically aged wine. Nitrogen compounds, including amino acids, biogenic amines, and ammonium chloride, were quantified, revealing strain-specific differences in nitrogen utilization and production. Proteomic analysis identified 1053 proteins, with 127 showing significant differences between strains. Strain G1 demonstrated enhanced cell wall remodeling and prioritized nitrogen conservation via arginine and lysine biosynthesis, while strain N62 exhibited increased translational activity and alternative carbon utilization pathways. Notably, strain N62 produced higher concentrations of biogenic amines (putrescine and tyramine), likely due to its greater decarboxylation capacity. Principal Component Analysis (PCA) highlighted clear differentiation in the nitrogen compound profiles across the base wine and wines inoculated with the two strains. The proteome of strain N62 showed increased mitochondrial activity and TCA cycle involvement, facilitating faster fermentation (27 days vs. 52 days for G1), growth (46 × 10⁶ cells/mL vs. 21 × 10⁶ cells/mL for G1) and cell viability (4 × 10⁶ cells/mL vs. 0.7 × 10⁶ cells/mL for G1). These findings suggest that yeast strain selection significantly influences nitrogen metabolism and potentially aroma profiles and and fermentation dynamics in sparkling wine production. Understanding these metabolic adaptations provides valuable insights for optimizing yeast performance to enhance wine quality and preserve regional characteristics.

Pituitary Tumours (PiTs) present significant challenges in diagnosis and treatments due to their heterogeneity, complex pathophysiology and endocrine comorbidities. Current therapies (i.e., surgery/radiotherapy/pharmacological treatment) frequently become ineffective over time, leading to low quality of life and high recurrence rates. Therefore, identifying alternative medical tools for these rare pathologies is crucial. The alteration of the telomerase/shelterin (TEL/SHEL) molecular complexes has been associated with cancer pathophysiology and progression; however, their role in PiTs remains poorly understood. Herein, we uncovered a profound dysregulation in the expression of key components of the TEL/SHEL systems in growth-hormone, adrenocorticotropic-hormone, and prolactin-hormone producing PiTs [GHomas (n = 50)/ACTHomas (n = 19)/PRLomas (n = 6), respectively] versus non-tumour pituitary tissues (n = 10), and identified critical dysregulated components in GHomas, ACTH, and PRLomas, some of them associated with key clinical features in GHomas (i.e., sinus-invasion/visual-alteration/cephalea, etc.). Presurgery treatment is likely not a confounding variable in the alterations observed in the TEL/SHEL system in PiTs. Moreover, we demonstrated that TEL activity inhibition (using BIBR1532) in primary-patient cell-cultures and cell-line models (GH3/AtT-20) might serve as a potential therapeutic tool by reducing cell-proliferation and stem-cell capacity through the modulation of key oncogenic processes, including GH/ACTH synthesis, cell-cycle, and DNA Damage Repair (DDR) pathways. Notably, we also demonstrated that BIBR1532, in combination with somatostatin-analogues, exerted a synergistic/additive anti-proliferative effect in GH3 and AtT-20 cells. Altogether, we demonstrate a profound TEL/SHEL-associated molecular dysregulation in GHomas and ACTHomas, which could serve as a potential source of novel diagnostic/prognostic biomarkers and therapeutic targets, offering a clinically relevant opportunity worth to be explored in humans.

Objective: An SF3B1 (Somatic splicing factor 3B subunit 1) mutation has been associated with prolactin-secreting pituitary neuroendocrine tumours (PitNET) with increased proliferation, invasion, dopamine agonist resistance and reduced progression-free survival. Design: We screened a multi-centric cohort of 127 patients with prolactin-secreting PitNET for the SF3B1R625H mutation using digital PCR. Methods: A comparative analysis was conducted between wild-type and mutated tumours, assessing clinical parameters, including age at diagnosis, sex distribution, prolactin levels, tumour size, extent of invasion, recurrence, and response to dopamine agonists. Results: Somatic SF3B1R625H mutation was found in 21/127 patients (17%), who were diagnosed at a younger age (p=0.04) and had larger tumour diameter (p=0.03). Patients who needed transcranial surgery had a higher mutation frequency in their tumour samples compared to the transsphenoidal group (p=0.01). The occurrence of mutation was similar in males and females. Preoperative and postoperative prolactin levels were comparable in patients with mutant and wild-type tumours. No associations were observed between mutation and tumour invasiveness, Ki-67 proliferation index, p53 expression, recurrence and dopamine agonist resistance. Hypopituitarism at presentation, visual deficits, number of surgeries and disease-free survival were not different between the groups. Conclusion: SF3B1 somatic mutation status in lactotroph tumours—as assessed by digital PCR technology—is associated with a younger age at diagnosis and larger tumour diameter. However, in our cohort it does not appear to associate with histological features, higher recurrence, treatment resistance, tumour invasiveness, or long-term outcomes in our multi-centric cohort.