Search Results (268)

Background: Autism spectrum disorder (ASD) represents a neurobiological disorder with a high prevalence in the children’s population. The aim of the present review was to assess the current evidence on the use of salivary biomarkers for the early diagnosis of ASD. Materials and methods: A search was conducted on the electronic databases PUBMED/Medline, Google Scholar and Scopus for the retrieval of articles concerning the study topic. Results: A total of 22 studies have been included in the present review considering 21 articles identified from databases and 1 article included using a manual search. A wide range of biomarkers have been proposed for early detection of ASD diseases including nonspecific inflammation markers like interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor α (TNFα), oxidative stress markers like superoxide dismutase and glutathione peroxidase, hormones such as cortisol and oxytocin, various microRNAs including miR-21, miR-132 and miR-137, and exosomes. The techniques used for biomarke detection may vary according to molecule type and concentration. Conclusions: salivary biomarkers could represent a potential useful tool for the primary detection of several systemic diseases including ASD, taking advantage of non-invasiveness and cost-effective capability compared to other biofluid-based diagnostic techniques. Full article

The ability of the neuropeptide oxytocin to affect glial cell function is receiving increasing attention. We previously reported that oxytocin at a low nanomolar concentration could inhibit both astrocytic Ca²⁺ signals and glutamate release. Here, we investigate the ability of oxytocin receptors to couple both inhibitory and stimulatory pathways in astrocytes, as already reported in neurons. We assessed the effects of oxytocin at concentrations ranging from low to high in the nanomolar range on intracellular Ca²⁺ signals and on the glutamate release in astrocyte processes freshly prepared from the striatum of adult rats. Our main findings are as follows: oxytocin could induce dual responses in astrocyte processes, namely the inhibition and facilitation of both Ca²⁺ signals and glutamate release; the inhibitory and the facilitatory response appeared dependent on activation of the G_i and the G_q pathway, respectively; both inhibitory and facilitatory responses were evoked at the same nanomolar oxytocin concentrations; and the biased agonists atosiban and carbetocin could duplicate oxytocin’s inhibitory and facilitatory response, respectively. In conclusion, due to the coupling of striatal astrocytic oxytocin receptors to different transduction pathways and the dual effects on Ca²⁺ signals and glutamate release, oxytocin could also play a crucial role in neuron–astrocyte bi-directional communication through a subtle regulation of striatal glutamatergic synapses. Therefore, astrocytic oxytocin receptors may offer pharmacological targets to regulate glutamatergic striatal transmission, which is potentially useful in neuropsychiatric disorders and in neurodegenerative diseases. Full article

Postmenopausal osteoporosis is estrogen-dependent and results in an imbalance between bone formation and resorption. The approved therapy is intended to reduce the risk and consequences of fractures, but still has a number of contraindications and associated adverse effects. Recently, oxytocin has been shown to have an anabolic effect on bone tissue, increasing the production of osteoblasts and inhibiting the activity of osteoclasts. Thus, this study aimed to examine the potential of oxytocin as a biomarker and therapeutic agent for postmenopausal osteoporosis. A PubMed search yielded 16 articles upon analysis of the inclusion and exclusion criteria. The results showed that, compared to women in the same age group without bone loss, those diagnosed with osteoporosis exhibited lower blood oxytocin levels, possibly related to a greater tendency towards fractures. The administration of oxytocin could be a promising strategy to enhance bone quality and, consequently, to reduce the incidence of fragility fractures; however, no human studies have been conducted regarding its use as a possible treatment. Thus, it is essential to increase the number of clinical trials in women with ovarian dysfunction and bone loss, in which oxytocin could become a viable therapeutic alternative. Full article

Background: Anhedonia, defined as the diminished capacity to experience pleasure, represents a core negative symptom in first-episode psychosis (FEP) with profound implications for functional outcomes and long-term prognosis. Despite its clinical significance, comprehensive understanding of anhedonia prevalence, underlying mechanisms, and optimal intervention strategies in early psychosis remains limited. Objectives: To systematically examine the prevalence and characteristics of anhedonia in FEP patients, explore neurobiological mechanisms, identify clinical correlates and predictive factors, and evaluate intervention efficacy. Methods: Following PRISMA 2020 guidelines, we conducted comprehensive searches across PubMed, Embase, PsycINFO, and Web of Science databases from January 1990 to June 2025. Studies examining anhedonia and negative symptoms in FEP patients (≤24 months from onset) using validated assessment instruments were included. Quality assessment was performed using appropriate tools for study design. Results: Twenty-one studies comprising 3847 FEP patients met inclusion criteria. Anhedonia prevalence ranged from 30% at 10-year follow-up to 53% during acute phases, demonstrating persistent motivational deficits across illness trajectory. Factor analytic studies consistently supported five-factor negative symptom models with anhedonia as a discrete dimension. Neuroimaging investigations revealed consistent alterations in reward processing circuits, including ventral striatum hypofunction and altered network connectivity patterns. Social anhedonia demonstrated stronger associations with functional outcomes compared to other domains. Epigenetic mechanisms involving oxytocin receptor methylation showed gender-specific associations with anhedonia severity. Conventional antipsychotic treatments showed limited efficacy for anhedonia improvement, while targeted psychosocial interventions demonstrated preliminary promise. Conclusions: Anhedonia showed high prevalence (30–53%) across FEP populations with substantial clinical burden (13-fold increased odds vs. general population). Meta-analysis revealed large effect sizes for anhedonia severity in FEP vs. controls (d = 0.83) and strong negative correlations with functional outcomes (r =·−0.82). Neuroimaging demonstrated consistent ventral striatum dysfunction and altered network connectivity. Social anhedonia emerged as the strongest predictor of functional outcomes, with independent suicide risk associations. Conventional antipsychotics showed limited efficacy, while behavioral activation approaches demonstrated preliminary promise. These findings support anhedonia as a distinct treatment target requiring specialized assessment and intervention protocols in early psychosis care. Full article

Pre-eclampsia (PE) is a hypertensive pregnancy complication. Oxidative stress is hypothesized to contribute to the pathophysiology of PE. Both the hydrogen sulfide (H₂S) and oxytocin (OT) systems might play a role in the pathophysiology of PE, like their antioxidant and hypotensive effects. Thus, the role of the interaction of the OT and H₂S systems in the context of PE was further elucidated in the present clinical case–control study “NU-HOPE” (Nürnberg-Ulm: The role of H₂S and Oxytocin Receptor in Pre-Eclampsia; ethical approval by the Landesärztekammer Bayern, file number 19033, 29 August 2019), comparing uncomplicated pregnancies, early onset PE (ePE, onset < 34 weeks gestational age) and late onset PE (lPE, onset > 34 weeks gestational age). Routine clinical data, serum H₂S and homocysteine levels, and tissue protein expression, as well as nitrotyrosine formation, were determined. The main findings were (i) unchanged plasma sulfide levels, (ii) significantly elevated homocysteine levels in ePE, but not lPE, (iii) significantly elevated expression of H₂S enzymes and OT receptor in the placenta in lPE, and (iv) significantly elevated nitrotyrosine formation in the lPE myometrium. Taken together, these findings suggest a role for the interaction of the endogenous H₂S- and OT/OTR systems in the pathophysiology of pre-eclampsia, possibly linked to impaired antioxidant protection. Full article

Background: Borderline personality disorder (BPD) is a severe psychiatric condition characterised by emotional instability, impulsivity, interpersonal dysfunction, and self-injurious behaviours. Despite growing clinical interest, the neuropsychological mechanisms underlying these symptoms are still not fully understood. This review aims to summarise findings from neuroimaging, psychophysiological, and neurodevelopmental studies in order to clarify the neurobiological and physiological basis of BPD, with a particular focus on emotional dysregulation and implications for the treatment of adolescents. Methods: A narrative review was conducted, integrating results from longitudinal neurodevelopmental studies, functional and structural neuroimaging research (e.g. FMRI and PET), and psychophysiological assessments (e.g., heart rate variability and cortisol reactivity). Studies were selected based on their contribution to understanding the neural correlates of BPD symptom dimensions, particularly emotion dysregulation, impulsivity, interpersonal dysfunction, and self-harm. Results: Findings suggest that early reductions in amygdala volume, as early as age 13 predict later BPD symptoms. Hyperactivity of the amygdala, combined with hypoactivity in the prefrontal cortex, underlies deficits in emotion regulation. Orbitofrontal abnormalities correlate with impulsivity, while disruptions in the default mode network and oxytocin signaling are related to interpersonal dysfunction. Self-injurious behaviour appears to serve a neuropsychological function in regulating emotional pain and trauma-related arousal. This is linked to disruption of the hypothalamic-pituitary-adrenal (HPA) axis and structural brain alterations. The Unified Protocol for Adolescents (UP-A) was more effective to Mentalization-Based Therapy for Adolescents (MBT-A) at reducing emotional dysregulation compared, though challenges in treating identity disturbance and relational difficulties remain. Discussion: The reviewed evidence suggests that BPD has its in early neurodevelopmental vulnerability and is sustained by maladaptive neurophysiological processes. Emotional dysregulation emerges as a central transdiagnostic mechanism. Self-harm may serve as a strategy for regulating emotions in response to trauma-related neural dysregulation. These findings advocate for the integration of neuroscience into psychotherapeutic practice, including the application of neuromodulation techniques and psychophysiological monitoring. Conclusions: A comprehensive understanding of BPD requires a neuropsychologically informed framework. Personalised treatment approaches combining pharmacotherapy, brain-based interventions, and developmentally adapted psychotherapies—particularly DBT, psychodynamic therapy, and trauma-informed care—are essential. Future research should prioritise interdisciplinary, longitudinal studies to further bridge the gap between neurobiological findings and clinical innovation. Full article

Animal-assisted services (AAS) have been shown in multiple studies to improve a range of human psychological and physical health benefits. The aim of this pilot study is to investigate simultaneously two psycho-physiological indicators of the valence of interactions in the context of dog-assisted activities in children diagnosed with autism spectrum disorder. Ten children and four dogs experienced in AAS were involved, lasting 90 days, in weekly one-hour sessions. Before and after each session, saliva was taken in both dogs and children for determination of salivary oxytocin and cortisol levels. In addition, at the end of the program, a questionnaire was administered to both parents and dog handlers to assess the impact of AAS in children and dogs. Our results revealed no statistically significant change in cortisol and oxytocin levels in dogs enrolled throughout the sessions, while an increasing trend was noted for salivary oxytocin in 50% of the dogs and for salivary cortisol in all dogs at the end of the AAS, when compared to the pre-AAS. Salivary cortisol measurement in children with an autistic neurotype highlighted a statistically significant increase at the end of the AAS when compared to the pre-AAS, but this was not observed for oxytocin level evaluations. Regarding the perception of the children’s parents about the effects of the program, our data reported an improvement in sociability of the children in 100 percent of the cases. Furthermore, dog handlers reported an absence of signs of stress in their dogs during the sessions. Although the perceived effectiveness and quality of AAS has been demonstrated in the literature, the need to carefully select the dogs involved, considering their skills and needs, is critical to ensure their well-being in various therapeutic settings. Full article

Primary dysmenorrhea (PD) is characterized by lower abdominal spasms and painful cramps during menstruation in females with a normal pelvic anatomy. Cymbopogon citratus (DC.) Stapf, commonly known as lemongrass, is consumed in the form of herbal tea around the world. It has been traditionally used for menstrual disorders in several communities. This study aims to evaluate the traditional use of C. citratus for its efficacy in alleviating the symptoms of PD. C. citratus extract (CcE) was chemically characterized using HPLC and GCMS, which indicated the presence of several phenolic compounds and long-chain fatty acids. The anti-inflammatory activity of CcE was assessed by COX-I, COX-II, and 5-LOX enzyme inhibition with IC₅₀ values of 143.7, 91.7, and 61.5 µg/mL, respectively, and showed good total antioxidant capacity and free radical scavenging activity. PD was induced in female Wistar rats by administering estradiol valerate followed by oxytocin to induce PD symptoms. CcE efficacy was assessed at 30, 100, and 300 mg/kg concentrations and compared with ibuprofen. CcE 300 mg/kg reduced abdominal contortions and inflammation in the rat uterus. The inflammatory (COX-II, TNFα and IL-10) and oxidative stress (TAC, TOS, MDA and SOD) markers in uterine tissue homogenate were also improved. An in vivo analgesic assessment through hot-plate, tail-flick, and acetic acid-induced writhing assays showed good analgesic activity by CcE, while ex vivo experiments described tocolytic effects in rat uterine muscles. CcE alleviates PD by its antioxidant, anti-inflammatory, analgesic, and tocolytic effects. Full article

Background/Objectives: Borderline personality disorder (BPD) is a complex psychiatric condition marked by emotional dysregulation, interpersonal instability, and impulsivity. Despite the advances in psychotherapy and pharmacotherapy, many patients show a partial or unstable response. Recent research suggests that oxytocin, a neuropeptide involved in social cognition and emotional regulation, may offer novel therapeutic avenues. Methods: We systematically synthesize evidence from PubMed, PsycINFO, Web of Science, and Google Scholar on oxytocin’s role in BPD, prioritizing studies on neurobiology, emotion regulation, clinical interventions, and adjunctive therapy models. Thirty studies were included and critically appraised using PRISMA and Cochrane’s tools. Due to methodological heterogeneity, no meta-analysis was conducted; instead, the findings were integrated through a narrative synthesis approach. Results: Evidence supports oxytocin’s modulatory effects on amygdala reactivity, prefrontal–limbic connectivity, and hypothalamic–pituitary–adrenal axis function. Intranasal oxytocin appears beneficial for emotional regulation and interpersonal sensitivity, particularly in individuals with early trauma. The reported effect sizes ranged from small (Cohen’s d ≈ 0.40) to large (d ≈ 0.83), though some trials reported null or adverse effects, such as increased hypermentalization. Heterogeneous responses were influenced by factors such as sex, trauma history, and OXTR gene variants. Conclusions: Although intranasal oxytocin shows promise in modulating core neurobiological systems implicated in BPD and enhancing emotion regulation and social cognition, its clinical effects remain variable and context-dependent. The evidence supports cautious exploration of oxytocin as an adjunct to psychotherapeutic interventions rather than as a standalone treatment. Future research should focus on biomarker-informed, stratified trials that account for trauma history, genetic variation, and sex differences to clarify its therapeutic potential. Full article

Shelter environments can be inherently stressful for dogs, a highly social species that forms strong attachment bond with humans. This study evaluated stress responses in 26 shelter dogs during routine veterinary examinations, analyzing behavioral scores alongside physiological and hormonal parameters, including heart rate, body temperature, cortisol (CRT), oxytocin (OXT), serotonin (5-HT), tryptophan (TRP), and interleukin-6 (IL-6). A significant negative correlation was observed between OXT and CRT (ρ = –0.540, p = 0.007), particularly in dogs exhibiting relaxed behavior. OXT was also negatively correlated with body temperature (ρ = –0.435, p = 0.034), supporting its potential role in modulating stress-induced hyperthermia. No significant associations were found between TRP, 5-HT, IL-6, or other physiological measures and behavioral scores. The absence of correlation between TRP and 5-HT may be due to blood–brain barrier regulation, while IL-6′s lack of association suggests further investigation is needed to clarify its role in canine stress responses. These findings highlight OXT’s possible buffering effect on the hypothalamic–pituitary–adrenal axis and suggest that behavioral assessment may offer a more sensitive measure of canine stress than hormonal or physiological parameters alone. Future studies with larger and more diverse samples are needed to confirm and expand upon these results. Full article

Background: The objective of this review is to demonstrate the efficacy of mifepristone as an inducing agent of labor by analyzing its impact on cervical maturation and maternal and neonatal outcomes. The research results showed that mifepristone facilitates cervical ripening and enhances uterine sensitivity. Methods: A narrative review of the literature was conducted to descriptively summarize and compare available data. No formal meta-analytic model was applied. The analysis was descriptive and based on pooled aggregated data without the use of inferential modeling. Studies published through November 2024 were retrieved using the Medline, Ovid, Scopus, and Web of Science databases. The search was based on a combination of keywords: “mifepristone”, “induction”, and “labor”. Randomized clinical trials and prospective and retrospective studies concerning full-term pregnancies with unfavorable cervices were included, while studies concerning termination of pregnancy or intrauterine death were excluded. The outcomes analyzed included cesarean section rates, neonatal intensive care unit admissions, and oxytocin and prostaglandin use. Results: Ten studies were analyzed, with a total of 1561 patients. The use of mifepristone showed a reduction in the use of oxytocin (RR = 0.84; 95% CI: 0.70–1.01), although this difference did not reach statistical significance (p = 0.065), and a highly significant reduction in prostaglandin use (42.7% vs. 78.9%; RR = 0.54; 95% CI: 0.48–0.60; p < 0.0001), with no significant difference in cesarean section rate (18.9% vs. 23.6%; RR = 0.80; 95% CI: 0.63–1.01; p = 0.068). However, a significantly higher rate of neonatal ICU admissions was observed in the mifepristone group (13.9% vs. 9.3%; RR = 1.48; 95% CI: 1.08–2.02; p = 0.014). Only studies excluding patients with a previous cesarean section were included for the analyses of cesarean sections, oxytocin, and prostaglandin use, while all studies were retained for NICU evaluation. Conclusions: Mifepristone represents a promising option for labor induction due to its ability to improve cervical maturation and reduce the need for additional uterotonic agents. Our pooled analysis confirmed a significant reduction in prostaglandin and oxytocin use, and a non-significant trend toward fewer cesarean deliveries. However, the observed increase in NICU admissions in the mifepristone group raises important concerns regarding neonatal safety. Further studies are needed to investigate whether this association reflects underlying clinical factors, variations in NICU admission policies, or a true pharmacological effect. Future research should focus on optimizing dosing regimens, identifying patient subgroups who benefit most, and clarifying neonatal outcomes through long-term follow-up. Full article

Background: Firefighters’ work exposes them to high levels of stress. Oxytocin (OXT) and corticotrophin-releasing hormone (CRH) are hormones released in response to stress. Prolonged exposure to stress can have negative effects, such as increased blood pressure and glucose levels, and a weakened immune system. Methods: This study involved 57 fire department cadets, randomly divided into craniosacral therapy (CS) and contralateral therapy (CO) groups. This study aimed to check whether 5-week craniosacral therapy affects CRH and OXT levels, determined from blood. Results: For the CS group, CRH_1 and CRH_2 showed slight increases in median values, 1.73 vs. 2.16, and OXT_1 and OXT_2 showed significant increases in median values, 54.71 vs. 57.77. Spearman’s correlation coefficient for CRH_1 vs. OXT_1 was r = 0.26, p = 0.124; similarly, for CRH_2 vs. OXT_2 was r = −0.02, p = 0.920; for CRH_ 1 vs. CRH_2 was r = 0.25, p = 0.173; and for OXT_1 vs. OXT_2 was r = 0.77, p < 0.00001. The values of the point statistics for CRH were similar in CO_1 and CS_1. After the end of therapy, in the CS_2 group, the values of the point statistics were greater than those for the CO_2 group. The median values for oxytocin in the CO_1 group were greater than those in the CS_1 group. After the end of therapy, in the CO_2 group, the values of the scoring statistics were smaller than those for the CS_2 group. The effect of the intervention in the CS group and the CO group showed a significance of p = 0.0003 and p = 0.023. Conclusions: After the end of therapy, a significant increase in OXT levels was observed, as well as a slight increase in CRH levels. Full article

A Lipophilic Prodrug Charge Masking (LPCM) strategy involves masking of hydrophilic peptide charges with alkoxycarbonyl groups, which are cleaved by esterases after intestinal absorption. This study investigates the LPCM strategy’s applicability to oxytocin (OT), a peptide with well-defined biological activity. A series of OT prodrugs with varying alkoxycarbonyl chain lengths (2 to 12 carbon atoms) were synthesized, and their permeability was assessed using parallel artificial membrane permeability assay (PAMPA) and Caco-2 cell culture models. The PAMPA results indicated that OT demonstrated poor permeability (P_app = 2.2 × 10⁻⁶ cm/s), while its prodrugs Hoc-OT, Oct-OT, and Dec-OT were characterized by significantly better permeability, with Dec-OT achieving a four-fold increase over OT. The prodrug with a 12-carbon chain (Dod-OT) exhibited poor permeability; however, its high mass retention suggests strong membrane affinity. Further evaluation, using the Caco-2 cell model, revealed a 1.8-fold higher P_app of Oct-OT compared to OT, indicating possible higher oral availability. Conversely, Hoc-OT exhibited lower permeability than OT. Our findings indicate that the LPCM strategy can effectively boost the oral bioavailability of certain peptides, paving the way for their transformation into bioavailable drugs. Full article

Background: Over recent years, several pain management techniques have been proposed to control labour pain, including pharmacological and non-pharmacological interventions. Transcutaneous electrical nerve stimulation (TENS) is considered a safe, non-invasive, easily applicable, and inexpensive pain relief method. This study aimed to investigate the impact of TENS on consecutive labour stages and on maternal and neonatal outcomes. Methods: This retrospective, single-centre cohort study covered a two-year period (1 January 2022–31 December 2023). A total of 1451 women met the inclusion criteria. TENS was applied in 203 of them. In 54.67% of cases, TENS was combined with water immersion and, in 42.85%, with water immersion and Entonox (N₂O and O₂ mixture). Two groups of patients that either made use of TENS, or not, to reduce labour pain, were compared to assess the effect of TENS on the course of labour and the condition of the newborn. Results: The women in the TENS group experienced a significantly longer first stage of labour. There was no statistically significant difference between the groups in terms of oxytocin usage, perineal tearing, episiotomy, and umbilical cord blood pH. The simultaneous application of TENS and water immersion contributed to prolonging the first stage of labour relative to their independent effects. Conclusions: The application of TENS may prolong the first stage of labour, without increasing the rate of perineal tearing and episiotomy and without any adverse effects on the condition of the newborn. Full article

Osteoarthritis (OA) remains a leading cause of disability worldwide, with no disease-modifying therapies currently available for treatment. The infrapatellar fat pad (IFP) harbors mesenchymal stem/stromal cells (MSC) with potent immunomodulatory and regenerative properties, making them a promising candidate for OA treatment. A growing body of evidence suggests that the therapeutic effects of MSC are largely mediated by their extracellular vesicles (EVs), which carry bioactive cargo that modulates inflammation and tissue repair. However, optimizing MSC-derived EVs as a cell-free therapeutic approach requires an in-depth understanding of how culture conditions and inflammatory/hormonal priming influence their functional properties. In this study, IFP-MSC were expanded in regulatory-compliant human platelet lysate (HPL) and xeno-/serum-free (XFSF) media and primed with an inflammatory/fibrotic cocktail (TIC) with oxytocin (OXT) to assess the impact on their immunophenotypic profile and EV cargo. The immunophenotype confirmed that TIC+OXT-primed MSC retained key immunomodulatory surface markers, while EV characterization verified the successful isolation of CD63+/CD9+ vesicles. Pathway enrichment analysis of both HPL- and XFSF- TIC+OXT EVs cargo identified key miRNAs associated with immune regulation, tissue repair, and anabolic signaling. Functional assays revealed that TIC+OXT EVs promoted M2-like anti-inflammatory macrophage polarization and exhibited chondroprotective properties in chondrocytes/synoviocytes inflammatory osteoarthritic assay. These findings highlight the therapeutic potential of TIC+OXT-primed IFP-MSC-derived EVs as immunomodulatory and chondroprotective agents, offering a promising strategy for OA treatment through a clinically viable, cell-free approach. Full article