High-grade serous ovarian cancer (HGSOC) is a leading cause of mortality from gynecologic malignancies worldwide. Although a transformative improvement has been shown with the introduction of PARP (poly(ADP-ribose) polymerase) inhibitors, the emergence of resistance to these drugs represents a therapeutic challenge. Hence, expanding our understanding of mechanisms behind the control of PARP1 expression can provide strategic guidance for the translation of novel therapeutic strategies. The Signal Transducer and Activator of Transcription (STAT) family of proteins consists of transcription factors critically involved in the regulation of important cellular functions. Notably, we recently demonstrated that, in cervical cancer cells, STAT1 controls PARP1 levels through multiple mechanisms, possibly involving also STAT3. Here, we tested the hypothesis that a similar mechanism might be operative in HGSOC. To this end, the impact of STAT1/STAT3 modulation on PARP1 expression was assessed in established and primary HGSOC cells, and molecular biology studies proved that STAT1 might act at both transcriptional and post-transcriptional levels to modulate the PARP1 level. Notably, bioinformatics analysis of TCGA databases demonstrated that increased STAT1 mRNA expression levels are associated with a favorable prognosis and with response to chemotherapy in HGSOC patients. Our findings suggest an alternative strategy for targeting HGSOC cells based on their dependency on PARP1.

Remifentanil is a potent ultra-short acting mu-opioid analgesic drug, frequently used in anaesthesia due to its favor-able pharmacodynamic and pharmacokinetic profile. It may be associated with the occurrence of hyperalgesia. Preclinical studies suggest a potential role of microglia, although the molecular mechanisms have not been fully elucidated. Considering the role of microglia in brain inflammation and the relevant differences among species, the effects of remifentanil were studied on the human microglial C20 cells. The drug was tested at clinically relevant concentrations under basal and inflammatory conditions. In the C20 cells, the expression and secretion of interleukin 6, interleukin 8 and the monocyte chemotactic protein 1 were rapidly induced by a mixture of pro -inflammatory cytokines. This stimulatory effect was sustained up to 24 h. Remifentanil did not exert any toxic effect nor modify the production of these inflammatory mediators, thus suggesting the lack of direct immune modulatory actions on human microglia.

Background: The interpretation of pediatric thyroid lesion represents a challenging diagnostic tool for fine-needle aspiration cytology (FNAC). As for the adult lesions, it represents the first diagnostic tool for correct characterization of these nodules. Recent data from the National Cancer Institute (NCI) have proven that the incidence of thyroid malignancy has been increasing, especially in adolescents. These data are mostly linked to an estimated higher prevalence of well-differentiated cancers with 90% diagnosed as papillary thyroid cancer; some specific malignant subtypes, such as diffuse sclerosing subtype, are more frequently diagnosed in children, with, not uncommonly, a more aggressive behavior, which justifies the increased number of surgical procedures. For this reason, the American Thyroid Association (ATA) recommended the performance of neck ultrasonography and FNAC in the evaluation of pediatric thyroid nodules. In this regard, the performance of an FNAC has high sensitivity and diagnostic accuracy in pediatric series, sharing the same problematic issues encountered in adult population, mostly in the diagnosis of the indeterminate lesions. Summary: Since 2023, the diagnosis of a pediatric lesion was based on the risk of malignancy used for the adulthood. The introduction of the third edition of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) introduced, for the first time, a specific adoption of diagnostic categories combined with their own and personalized ROM and management in pediatric thyroid lesions. In this review, we focused on the analysis of the ROM and data from literature hinged on the evaluation of the adoption of the 3rd edition of TBSRTC in pediatric thyroid lesions. Key Message: Briefly, the primary source of the reviewed publications was the PubMed, Scopus, and Web of Science database using the keywords (thyroid) and (carcinoma or neoplasm or cancer) AND (Bethesda or TBSRTC) and (Paediatric). The search consisted of literature published from January 2023 to September 2025 with the objective of calculating the risk of malignancy for III, IV, V, and VI diagnostic categories of the 3rd edition of TBSRTC in pediatric group. We limited our search to English-language articles.

In the FMR1 gene, expansion of the CGG triplet beyond 200 repeats triggers DNA methylation, resulting in the Fragile X Syndrome (FXS). There exist rare individuals who carry a CGG expansion >200 that remains unmethylated, rescuing them from expressing the FXS phenotype. We tested the hypothesis that active FMR1 transcription regulates DNA methylation of the locus through the binding of its mRNA to DNMT1 enzyme. Our results show that DNMT1 binds FMR1–mRNA in transcriptionally active cells preventing them from being methylated, whereas it binds to the FMR1 locus in FXS cells, resulting in gene silencing. DNMT1 binds to the transcript or to the locus after reactivating or blocking FMR1 transcription using specific drugs, respectively. As proof of concept, aptamers capable of binding and inhibiting DNMT1 were shown to reactivate the silenced FMR1 gene. We propose that DNMT1 represents a specific molecular target to reactivate the FMR1 gene expression.