Background/Objectives: Endometriosis (END) is a painful gynecological condition. Clinical examination, imaging, and laparoscopy can provide a definitive diagnosis of END. Nonetheless, non-invasive biomarkers could help enhance and streamline the diagnostic process. Micro-RNAs (miRNAs), a family of small non-coding RNAs, could serve as useful non-invasive biomarkers for END. The aim of this study was to perform serum miRNA profiling in a retrospective cohort of women to identify miRNAs that are differentially expressed in END compared to control patients. Methods: RNA was isolated from serum samples of 67 END patients and 60 control women. The expression profile of a 754-miRNA panel was studied with RT-qPCR performed on a QuantStudio 12K Flex with the TaqMan OpenArray miRNA panel. A Censored Regression Model was used for miRNA differential expression analysis. Several gene-enrichment algorithms were employed to identify pathways related to the target genes of differentially expressed miRNAs. Results: One hundred and thirty miRNAs were detected in at least 75% of samples from either the END or the control group. Sixteen miRNAs were significantly modulated between the END and control groups. Enrichment analysis identified targets significantly overrepresented in numerous pathways involved in biological processes related to END, including inflammation, angiogenesis, cellular invasion, cell-cycle/cell proliferation, and estrogen and progesterone hormonal signaling. Conclusions: Our study indicates that differentially expressed miRNAs between END patients and controls can be identified through liquid biopsy. Our findings also suggest a potential role for serum miRNAs in the pathophysiology of END, warranting further investigations for their use as non-invasive biomarkers.

Psychiatric disorders represent a leading cause of disability worldwide and are characterized by substantial biological and therapeutic heterogeneity. Despite significant research efforts, peripheral biomarkers capable of guiding diagnosis, patient stratification, and personalized treatment selection are still lacking. Circulating cell-free DNA (cfDNA) has recently emerged as a promising candidate biomarker, as it may integrate signals of cellular damage, apoptotic activity, and immune activation across multiple tissues. Beyond its role as a marker, cfDNA may also actively contribute to disease processes by functioning as a damage-associated molecular pattern (DAMP), thereby perpetuating inflammatory signaling. The mitochondrial component of cfDNA (cf-mtDNA), which also possesses strong immunostimulatory properties, represents a particularly sensitive indicator of mitochondrial vulnerability to stress. In this context, the present review aims to synthesize the most recent evidence on cfDNA and cf-mtDNA in major psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ). Specifically, we examine their association with psychological stress exposure and childhood trauma, as well as their involvement in inflammation-related pathophysiological mechanisms such as mitochondrial dysfunction, oxidative stress, and hypothalamic–pituitary–adrenal (HPA) axis dysregulation. Available evidence suggests that alterations in cfDNA may be present in subgroups of patients with MDD, BD, and SCZ. However, findings remain heterogeneous and sometimes contradictory, partly due to methodological limitations, including the lack of standardized analytical protocols and insufficient control for potential confounders. Nevertheless, cfDNA holds promise as a tool for inflammation-based patient stratification and for informing personalized therapeutic strategies. Future research directions include the integration of cfDNA within multi-omics frameworks, the analysis of cfDNA methylation profiles to infer tissue of origin, and the exploration of pharmacological strategies aimed at modulating cfDNA as a potential therapeutic target.

Borderline personality disorder (BPD) is characterized by emotion dysregulation, interpersonal dysfunction, and frequent non-suicidal self-injury (NSSI). Altered pain sensitivity in BPD has raised interest in the possible role of the endogenous opioid system, but only a few studies have explored β-endorphin, one of the major endogenous opioid peptides, in this disorder. Here we investigated serum β-endorphin levels in patients with BPD, their association with clinical features, and their longitudinal changes during psychotherapy. Forty-nine patients with BPD enrolled in the CLIMAMITHE randomized controlled trial and 25 age- and sex-matched unaffected controls were included. Serum β-endorphin concentrations were measured by ELISA at baseline in all participants and also after 6 and 12 months of treatment in patients receiving metacognitive interpersonal therapy or structured clinical management. Baseline β-endorphin levels did not differ between patients and controls and were not associated with symptom severity, interpersonal functioning, attachment style, psychotropic treatment, or NSSI. No overall longitudinal changes were observed during psychotherapy. However, responders showed a significant increase in β-endorphin levels from T0 to T12 (p = 0.016), whereas non-responders remained unchanged. Moreover, responders exhibited significantly lower baseline β-endorphin concentrations than non-responders (p = 0.001), and baseline levels showed potential discriminative value for treatment response (AUC = 0.806, p = 0.002) and correlated with changes in emotion dysregulation during treatment, measured through the DERS (r = 0.344, p = 0.040). In conclusion, these findings suggest that peripheral β-endorphin is unlikely to represent a trait biomarker of BPD but may be associated with response to psychotherapy, although its potential clinical relevance requires validation in larger independent cohorts.