Search Results (5,482)

SOX (SRY-related HMG-box) transcription factors are key regulators of embryogenesis and vascular development, with emerging roles in cancer biology. In non-small-cell lung cancer (NSCLC), the contributions of SOX18 and SOX30 remain insufficiently understood, particularly regarding their epigenetic regulation and network interactions with angiogenic and immune-modulatory pathways. We examined 800 NSCLC specimens (400 lung adenocarcinomas, 400 squamous cell carcinomas) using immunohistochemistry, RT-qPCR, Western blotting, and spatial transcriptomics to profile SOX18, SOX30, and related signaling partners (SOX7, SOX17, MEF2C—Myocyte Enhancer Factor 2C, VCAM1—Vascular Cell Adhesion Molecule 1, p-STAT3—Signal Transducer and Activator of Transcription 3). Epigenetic regulation was assessed via droplet digital methylation-specific PCR of promoter CpG islands, while functional validation employed adenoviral delivery of hsa-miR-24-3p in NSCLC cell lines and 3D spheroid cultures. SOX18 protein was markedly overexpressed in both NSCLC subtypes, despite reduced transcript levels and consistent promoter hypermethylation, suggesting post-transcriptional regulation. In contrast, SOX30 expression was uniformly downregulated at both mRNA and protein levels, frequently linked to promoter hypermethylation, especially in squamous carcinoma. Spatial transcriptomics revealed SOX18 enrichment at tumor cores and invasive borders, co-localizing with MEF2C, VCAM1, and p-STAT3 in vascular and stromal niches, while SOX30 expression remained low across all tumor regions. Functional assays demonstrated that hsa-miR-24-3p suppressed SOX18 expression and partially modulated SOX30 and MEF2C, reinforcing a miRNA-driven regulatory axis. In summary, SOX18 and SOX30 play divergent roles in NSCLC progression: SOX18 functions as a pro-oncogenic factor driving angiogenesis and tumor–stroma interactions, while SOX30 acts as an epigenetically silenced tumor suppressor. Regulation of SOX18 by miR-24-3p highlights a potential therapeutic vulnerability. These findings underscore the significance of SOX transcription factors as biomarkers and potential targets for novel treatment strategies in NSCLC. Full article

Background: Alzheimer’s Disease (AD) is the most common form of dementia and is characterized by progressive cognitive decline and neurodegeneration. In Italy, AD represents a major public health and socio-economic challenge. This review aims to summarize current Italian research on pharmacological and non-pharmacological interventions, including preclinical studies, clinical trials, rehabilitative approaches, and emerging neuromodulation techniques, highlighting contributions and future directions. Methods: A narrative review of the literature was conducted, focusing on Italian preclinical and clinical studies, observational and real-world evidence, cognitive and physical interventions, music therapy, non-invasive brain stimulation (rTMS, tDCS, tACS), and digital or home-based rehabilitation programs. Results: Italian research has explored different pharmacological strategies, including multitarget compounds, eptastigmine, rotigotine, and combinatorial therapies (donepezil-memantine, citicoline addition). Non-pharmacological interventions, such as cognitive stimulation, motor rehabilitation, music therapy, and multidimensional programs, demonstrated benefits on cognition, behavior, daily functioning, and caregiver well-being. Non-invasive neuromodulation techniques, targeting the dorsolateral prefrontal cortex and precuneus, showed promising effects on memory, attention, and executive functions, especially when combined with cognitive training. Digital health technologies, including telerehabilitation and home-based brain stimulation programs, further enhanced accessibility and adherence. Challenges remain due to fragmented research, small sample sizes, and limited standardization. Conclusions: Italian research on AD reflects a growing emphasis on integrated, multidimensional, and technologically advanced approaches. Strengthening preclinical studies, promoting multicenter collaborations, and combining pharmacological, cognitive, and neuromodulatory strategies may enhance therapeutic efficacy and patient quality of life. Continued investment in innovation and multidisciplinary research positions Italy to contribute meaningfully to global AD management and prevention. Full article

Background: Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) of the oral cavity is a chronic, rapidly developing mucosal lesion with an unclear pathogenesis, manifesting as a solitary ulcer. Given the malignant clinical appearance of the lesions, it is crucial to ensure the accuracy of the diagnosis to avoid unnecessary invasive surgical interventions. Methods: We present a case involving a 69-year-old female affected by a wide, painful ulcer on the left margin of the tongue. An incisional biopsy was performed, and histopathological examination confirmed the diagnosis, revealing a neutrophilic inflammatory infiltrate with components of eosinophils and lymphocytes. Considering the condition’s reactive and inflammatory nature, we planned a corticosteroid treatment with intralesional injections of triamcinolone acetonide. This therapy delivers the active principle directly to the tissues beneath the ulcerative lesion. Results: In three treatment sessions, we achieved the complete regression of the lesion’s signs and symptoms. During a one-year follow-up period, no recurrences were reported. Conclusions: The scarcity of documented cases and the ambiguity of definitions in the scientific literature highlight the importance of clinical reports, which refine scientific knowledge about this condition. At the same time, we record an effective and non-invasive treatment that could facilitate healthcare professionals in managing these types of oral pathologies. Full article

Background: Chemoresistance, particularly to cisplatin, remains a significant challenge in treating high-risk neuroblastoma, resulting in a mere 20% five-year overall survival rate. Tumour-derived small extracellular vesicles (sEVs) have been implicated in cancer progression by promoting angiogenesis, invasion, and proliferation in recipient cells. This study investigated alterations in the protein cargo of sEVs secreted by cisplatin-sensitive and resistant neuroblastoma cells and their impact on reprogramming non-cancerous recipient cells. Methods: sEVs from cisplatin-resistant (KellyCis83) and its cisplatin-sensitive parental cell line (Kelly) were isolated and characterised, followed by proteomic profiling and Gene Set Enrichment Analysis. Functional assays using human umbilical vein endothelial cells (HUVECs) evaluated the effects of sEVs on proliferation, migration, tube formation, and metabolism. The clinical relevance of the shortlisted sEV glycolytic proteins was evaluated using the R2 Genomics Analysis and Visualisation Platform. Results: Proteomic analysis revealed dysregulated metabolic pathways in KellyCis83 sEVs. While Kelly’s and KellyCis83’s sEV-induced aerobic glycolytic rates were similar, oxidative phosphorylation (OXPHOS) was significantly reduced in HUVECs treated with Kelly’s sEVs compared to KellyCis83’s sEVs, which might have been due to an altered balance of glycolytic enzymes in sEVs. Under angiogenic-factor-deprived conditions, the uptake of sEVs by HUVECs reduced their proliferation and increased anchorage-dependent differentiation. Our study demonstrated the enrichment of the MYCN oncogene and clinically relevant glycolytic proteins in neuroblastoma cell-derived sEVs. Conclusions: This study reports a potential mechanism by which sEVs derived from cisplatin-resistant neuroblastoma cells modulate endothelial cell function through alterations in metabolic pathways and provides an opportunity to explore exosomal MYCN and glycolytic proteins as circulating biomarkers for progression and treatment response signatures, using less invasive methods and enabling personalised treatment approaches for neuroblastoma patients. Full article

Introduction: Infrared thermography (IRT) is a non-invasive, non-ionizing imaging modality capable of rapidly capturing surface temperature variation. In dentistry, particularly orthodontics and TMD evaluation, IRT may serve as a valuable complementary tool to be added in conventional diagnostic protocols. Objective: Correlate possible relationships between thermographic findings of orofacial structures and cephalometric landmarks. Methods: An infrared imaging camera, FLIR^® i7, was used to record the regions of interest, correspondent to the temporal, masseter and orbicular oris muscles, in adolescents (n = 22). Bilateral temperature differences were considered as thermal asymmetries with a conventional threshold of 0.3 °C to distinguish an eventual hyperactivity or hyperfunctions of detrimental structures. The Trevisi cephalometric parameters that were taken into consideration for the study were SNA, SNB, ANB, OccltoSn, Wits relation to base and Molar/canine classes. Results: Most of the participants showed a normal temperature difference ΔΤ for the upper and lower orbicular oris muscle, right vs. left, 96% and 92%, respectively. The other ROIs presented a mixed pattern of thermal asymmetries; however, no statistically significant differences were found when crossed with the cephalometric landmarks. Conclusions: Asymmetrical patterns of infrared thermography can aid on the diagnosis and treatment plan of an orthodontic appointment, since the actual stability of pos-orthodontic treatment is highly dependent on the muscular activity of the tongue and lips, in particular when the patient has atypical swallowing. Our findings suggest that this technique can be used to quantify anatomical landmarks relevant to craniofacial morphology in specific populations, particularly at ages where muscular functional activity is strongly correlated with dentoskeletal development. Full article

Diaphragmatic paralysis (DP) in neonates is a rare yet potentially life-threatening cause of respiratory distress, often resulting from obstetric trauma or cardiac surgery. This report presents two distinct cases of bilateral DP: one following a dystocic delivery with associated brachial plexus involvement, and the other linked to a genetic mutation (SYNGAP1) in a neonate with no birth trauma. Diagnosis was established through imaging, fluoroscopy, electromyography, and genetic testing. In both cases, conservative management was initially pursued; however, due to persistent respiratory failure, invasive interventions were required. The first patient underwent bilateral diaphragmatic plication with favorable outcomes, while the second required tracheostomy due to poor response to non-invasive ventilation with good outcome. These cases highlight the diagnostic and therapeutic challenges of neonatal DP, emphasizing the need for individualized treatment strategies in the absence of standardized guidelines. Early diagnosis and a multidisciplinary approach are crucial to optimize respiratory outcomes and reduce complications from prolonged mechanical ventilation. Full article

Background: Maintaining an adequate mean arterial pressure (MAP) and cerebral perfusion pressure to ensure proper perfusion and oxygen delivery to all major organs is crucial—especially for neurosurgical patients after subarachnoid hemorrhage or traumatic brain injury—for preventing secondary brain damage or delayed cerebral ischemia. Currently, most neurosurgical intensive care units rely on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) values to guide therapy. Fluid resuscitation and norepinephrine are standard treatments for achieving a CPP between 60 and 70 mmHg; however, patients sometimes experience norepinephrine-refractory hypotension. In such cases, vasopressin is often the preferred medication; it is widely utilized and has gained interest in treating septic shock or refractory hypotension following cardiac surgery or hypovolemic shock. Recent studies have also shown the significant impact of vasopressin on resuscitation after traumatic brain injury (TBI) and its effect on CPP during ICU care. Nevertheless, little is known about how vasopressin affects cerebral perfusion and oxygenation, especially in patients with subarachnoid hemorrhage. Methods: This preliminary retrospective single-arm study examined how vasopressin affects P_btO₂ and cerebral blood flow using the non-invasive QuantixND^® device. After administering vasopressin for treating catecholamine-refractory hypotension, MAP, CPP, ICP, P_btO₂, and cerebral blood flow were measured over a 20-min period. Results: In this small cohort, vasopressin sufficiently improved MAP and CPP over a 20 min period following AVP bolus administration with a slight decline at later time points. The ICP decreased throughout this period, indicating some level of autoregulation. In contrast, cerebral blood flow did not improve despite the rise in CPP, and P_btO₂ levels remained below 20 mmHg. Conclusions: We conclude that vasopressin could be a viable option for maintaining MAP and CPP, but caution should be exercised in patients with already impaired cerebral perfusion. Furthermore, relying solely on CPP as the therapeutic guide in subarachnoid hemorrhage patients appears to be at least questionable. Full article

Alcohol’s chronic neurotoxic and degenerative effects mediate alcohol-related brain damage (ARBD), which is marked by neurobehavioral, cognitive, and motor deficits. Major underlying abnormalities include impairments in signaling through the insulin and insulin-like growth factor (IGF) pathways, which regulate energy metabolism. This study examined the potential role of dysregulated incretin network-related mechanisms as mediators of ARBD and evaluated a non-invasive serum exosome (S-EV)-based approach for detecting brain abnormalities. Frontal lobe tissue and S-EVs isolated from Long–Evans adolescent rats maintained for 2 weeks on control or 24% ethanol (caloric) containing liquid diets (n = 8/group) were analyzed using multiplex magnetic bead-based enzyme-linked immunosorbent assays (ELISAs). ARBD was associated with significantly reduced insulin, C-peptide, glucagon, ghrelin, leptin, GIP, and amylin levels in the frontal lobe and/or S-EV samples. In contrast, chronic ethanol exposure had no significant effects on PP, PYY, or GLP-1, and it did not increase proinflammatory cytokine expression. Chronic ethanol feeding broadly affected (primarily inhibiting) the expression of metabolic hormones linked to insulin/IGF signaling. The reductions in GIP and amylin suggest potential targets for therapeutic intervention to enhance brain energy metabolism via insulin networks. On the other hand, the findings suggest that GLP-1 receptor agonists may have limited efficacy in remediating the effects of ARBD. Finally, the results support the use of non-invasive S-EV assays to detect and guide treatment for metabolic brain dysfunction in ARBD. Full article

Background/Objectives: Granzyme B (GZB) PET Imaging is a non-invasive tool that can determine tumoral and systemic effects in immunotherapy. We aim to evaluate ⁶⁸Ga-NOTA-CYT-200 PET Imaging as a molecular imaging approach to determine CAR T-cell therapy response in a human melanoma mouse model. Our goal is to provide a method to monitor CAR T-cell therapy for patients with melanoma and other solid tumors. Methods: A human melanoma mouse model was generated by implanting naïve NSG mice (n = 28) with a human melanoma cell line (A375) subcutaneously (s.c.). After tumor implantation, mice were randomly assigned to receive either the treatment (CAR T) or vehicle solution (controls). After treatment, tumor sizes were measured every other day up to 35 days after cell implantation. ⁶⁸Ga-NOTA-CYT-200 PET Imaging was performed on days 2, 7, and 14 after CAR T-cell administration to assess T-cell activity within the tumors and organs. The PET Imaging results were correlated with IHC and immunofluorescent staining and cytokine assessment of tumor samples. Results: Tracer uptake within tumors of the CAR T group was significantly greater on days 2 (3.1 ± 1.2 vs. 1.1 ± 0.4, p = 0.002) and 7 (2.0 ± 1.1 vs. 1.1 ± 0.1, p = 0.01) after treatment, even before the CAR T group first presented with significantly lower tumor volumes on day 11 after treatment (61.8 mm³ ± 8.7 vs. 287.1 mm³ ± 157.6, p = 0.05). GZB (p = 0.03) and CAR T (p = 0.001) staining were also significantly greater in tumors of CAR T-cell-treated mice. Inflammatory cytokines such as IFN gamma (p = 0.03), CXCL10 (p = 0.004), and CCL5 (p = 0.02) concentrations were also significantly greater in CAR T-cell-treated tumors. Conclusions: CAR-T-treated tumors show significantly elevated ⁶⁸Ga-NOTA-CYT-200 uptake compared with controls, consistent with enhanced effector activity. Full article

Background/Objectives: Late diagnosis hampers effective treatment of non-small cell lung cancer (NSCLC). This study evaluated whether circulating microRNAs (miRs), miR-155 and miR-3196, measured in liquid biopsy peripheral blood mononuclear cells (PBMCs), can serve as potential non-invasive biomarkers for NSCLC diagnosis, patient stratification, therapy monitoring, and prognosis. Methods: RNA was isolated from PBMCs of 136 NSCLC patients and 64 healthy donors. RT–qPCR quantified miR expression in PBMCs after predefined QC filtering: miR-155-3p (NSCLC n = 63; controls n = 28), miR-3196 (NSCLC n = 55; controls n = 28), and miR-155-5p (NSCLC n = 23; controls n = 12). Diagnostic performance was assessed using receiver operating characteristic (ROC) analyses, reporting area under the curve (AUC), and threshold-dependent sensitivity/specificity. Survival was analyzed with Kaplan–Meier/Cox methods. Associations with clinicopathological variables (stage, metastasis, smoking, EGFR, and KRAS status), treatment response (chemotherapy, immunotherapy, TKIs), and survival outcomes were examined. Results: miR-155-3p was upregulated in NSCLC, whereas miR-3196 was downregulated relative to controls; AUCs were 0.881 and 0.784, respectively. At high-sensitivity operating points, specificity was lower (≈29–30%), consistent with PBMC miRs reflecting both immune activation and tumor burden. In adenocarcinoma, miR-155-3p was associated with advanced stage, metastatic disease and smoking history. miR-3196 aligned with features of metastatic progression. During systemic therapy (chemotherapy, immunotherapy, TKIs), circulating levels of both miRs tended to normalize. Notably, normalization of miR-155-3p levels was associated with improved overall survival, supporting its prognostic value and utility for treatment monitoring. Conclusions: Circulating miR-155-3p and miR-3196 in PBMCs are promising screening/monitoring non-invasive candidates rather than stand-alone NSCLC diagnostics at current thresholds. Combining these miRs with additional biomarkers and/or clinical covariates and tuning decision thresholds may enhance specificity for diagnostic use. While preliminary, these findings warrant validation in large, prospective studies with standardized protocols to enable clinical implementation. Full article

Diabetes is a significant risk factor for bisphosphonate-related osteonecrosis of the jaw (BRONJ), a severe oral complication with limited treatment options. Salivary testing offers a noninvasive approach for monitoring BRONJ risk; however, few studies have investigated salivary biomarkers in BRONJ. This study screened salivary biomarkers that reflect the progression of BRONJ under diabetic conditions. A diabetic BRONJ rat model was established to screen for diabetes-related biochemical biomarkers in saliva. Streptozotocin (STZ) administration elevated blood glucose and glycated albumin levels and altered lipid and renal function markers, confirming diabetes induction. Subsequent zoledronic acid (ZA) administration and extraction of the maxillary first molar delayed epithelialization, inflammatory cell infiltration, bone exposure, and necrosis in extraction sockets, indicating successful establishment of a diabetic BRONJ model. This model showed reductions in submandibular and sublingual gland size, as well as in acinar cell number. Although salivary secretion volume was reduced, saliva samples were successfully collected from all groups. Screening identified elevated urea nitrogen (UN) and total ketone bodies (T-KB) in the STZ + ZA group. These findings suggest that salivary UN and T-KB may reflect disease progression and serve as potential biomarkers for predicting BRONJ risk under diabetic conditions. Full article

Background: Interstitial lung diseases (ILDs) often progress quickly and are associated with a poor prognosis. New noninvasive biomarkers to assist in the classification and prognostication of ILD are needed. Exhaled nitric oxide (FeNO), Cavity nitric oxide (CaNO), and carbon monoxide (eCO) are biomarkers of airway inflammation, widely used in respiratory inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD). However, their value in ILD remains unclear. Objective: To evaluate the potential diagnostic and prognostic value of FeNO, CaNO, and eCO in ILD, and explore their integration into clinical practice. Methods: A total of 237 patients were recruited for the study, including 14 with idiopathic pulmonary fibrosis (IPF), 46 with interstitial pneumonia with autoimmune features (IPAF), 19 with mixed connective tissue disease–associated ILD (MCTD-ILD), 65 with polymyositis/dermatomyositis-associated ILD (PM/DM-ILD), 17 with rheumatoid arthritis-associated ILD (RA-ILD), 7 with systemic lupus erythematosus-associated ILD (SLE-ILD), 19 with Sjögren’s syndrome-associated ILD (SS-ILD), and 50 with systemic sclerosis-associated ILD (SSc-ILD). Multiple-flow FeNO and eCO analyses were performed in this population. The associations of these biomarkers with pulmonary function, acute exacerbations, and radiologic fibrosis classification were evaluated. Results: Patients with IPF exhibited significantly higher levels of FeNO at 50 mL/s (FeNO50) compared to those with connective tissue disease-associated ILD (CTD-ILD) and IPAF. Both CaNO and eCO were negatively correlated with pulmonary function parameters, particularly forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO). Receiver operating characteristic (ROC) curve analysis indicated that CaNO is a reliable biomarker for acute exacerbation, with an area under the ROC curve (AUC) of 0.8887, and a cutoff value of 6.35. Additionally, CaNO > 6.35 was associated with a relative risk (RR) of 12.87 for acute exacerbation (AE) compared to CaNO ≤ 6.35. Moreover, both CaNO and eCO levels were significantly higher in the fibrotic ILD group compared to the non-fibrotic group, with ROC analysis indicating AUCs of 0.7173 for CaNO and 0.6875 for eCO. Conclusions: FeNO, CaNO, and eCO can provide strong support for the early diagnosis and monitoring of ILD, especially with CaNO playing a crucial role in predicting acute exacerbations. Integrating these biomarkers into clinical practice can help doctors more accurately assess the progression of ILD and develop personalized treatment plans, ultimately improving the prognosis of ILD patients. Future research is needed to validate the effectiveness of these biomarkers in clinical management, facilitating their integration as standard tools for clinical monitoring. Full article

Background and Objectives: Glaucoma is a leading cause of irreversible blindness, and lowering intraocular pressure (IOP) is the only proven strategy to slow disease progression. We evaluated the clinical efficacy and safety of Micropulse Laser Trabeculoplasty (MLT) in patients with open-angle glaucoma and ocular hypertension, focusing on IOP control, visual function, and adverse events. Materials and Methods: This longitudinal, real-world cohort included 80 patients (132 eyes) treated with MLT between 2018 and 2025 at the Ophthalmology Clinic of the County Emergency Hospital, Bihor. Micropulse laser trabeculoplasty was applied over 360°, except in selected cases (90–300°), depending on anatomical or clinical factors. Outcomes included IOP by Goldmann and non-contact tonometry, best-corrected visual acuity (BCVA), refraction, and safety events. Pre-/post comparisons used paired tests and McNemar’s exact test where appropriate. Results: IOP decreased from 18.15 ± 5.02 to 15.57 ± 3.78 mmHg at 3 months (mean reduction: 2.58 mmHg, p < 0.001), confirmed by GEE adjusted for age, sex, and eye laterality. The proportion of eyes within target ranges increased significantly (IOP ≤ 18 mmHg and ≤21 mmHg; p = 0.0014 and p = 0.0023, respectively). A total of 31.1% of eyes achieved ≥ 20% IOP reduction, and 31.8% had an absolute decrease > 3 mmHg. BCVA and refraction remained stable (p > 0.05). No major complications or IOP spikes > 5 mmHg occurred; transient, self-limited events were uncommon. Conclusions: MLT was associated with a safe and clinically relevant reduction in IOP in patients with open-angle glaucoma and ocular hypertension, with stable visual function and minimal adverse effects observed. These results suggest that MLT may be a useful option for IOP management; however, the lack of a control group limits causal interpretation. Further controlled studies are warranted to confirm these findings. Full article

Background: Hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia, affect up to 10% of pregnancies worldwide and remain a leading cause of maternal and perinatal morbidity and mortality. These conditions are associated with adverse fetal outcomes, including preterm birth, growth restriction, and maternal complications such as stroke, eclampsia, multi-organ dysfunction, and a higher risk of long-term cardiovascular complications. Current management relies largely on intermittent blood pressure monitoring and assessment of symptoms, approaches that provide limited insight into the complex hemodynamic alterations underlying HDP. Objective: This narrative review aims to synthesize the available evidence on noninvasive cardiography through thoracic electrical bioimpedance (TEB) as a tool for maternal hemodynamic monitoring in pregnancy, with a focus on hypertensive disorders. Specifically, we (1) describe maternal cardiovascular adaptations in normal gestations and their disruption in HDP, (2) provide an overview of thoracic electrical bioimpedance cardiac output (TEBCO) technology, (3) summarize validation studies in pregnant populations, (4) explore potential clinical applications, including diagnostic support, therapeutic guidance, fluid management and postpartum surveillance, and (5) identify key limitations and research priorities for future practice. Conclusions: Noninvasive cardiography through thoracic electrical bio-impedance is an underutilized tool in the medical field. As an alternative to invasive assessment, TEBCO can identify underlying pathologic hemodynamic changes susceptible to treatment and allow monitoring of hemodynamic trends. The implementation of TEBCO would allow pathophysiologic-based treatments, improve clinical response to therapy, and lead to potential prolongations of pregnancy and cost-savings in healthcare. Current evidence is limited by small sample sizes, device variability, and lack of outcome-based trials. Future research should focus on standardized validation, multicenter studies, and interventional trials to determine whether non-invasive cardiography-guided care can improve maternal and neonatal outcomes. Full article

Background: Erectile dysfunction (ED) affects approximately 20% of men worldwide, significantly affecting their quality of life. While phosphodiesterase type 5 inhibitors (PDE5-Is) are the standard first-line treatment, a substantial number of patients are non-responders. Second-line treatments, such as intracavernosal alprostadil, are effective but often limited by their invasive nature and the need for frequent injections. Intracavernosal onabotulinumtoxinA (BoNT-A) offers a promising new option. By inhibiting acetylcholine release and norepinephrine, as well as other neurotransmitters involved in detumescence, it facilitates cavernosal smooth muscle relaxation and enhances penile blood flow. Its effects may persist for up to six months following a single injection, potentially reducing treatment burden and improving adherence among men with refractory ED. Methods: A systematic review was performed in accordance with the PRISMA guidelines. Literature searches were conducted in PubMed, Embase, Cochrane Library, Scopus, and Clinicaltrials.gov from inception until August 2025 using a combination of keywords and MeSH terms related to ‘erectile dysfunction’ and ‘botulinum toxin’. After screening, 51 studies met the inclusion criteria. Due to significant heterogeneity in interventions (e.g., BoNT-A dosage, co-therapies), patient populations, and reported outcomes, the data were not suitable for meta-analysis. Consequently, a narrative synthesis was performed to summarize the findings. Results: Among the included studies, intracavernosal BoNT-A was associated with improvements in validated erectile function scores. Reported response rates, variably defined across studies, ranged from 40% to 77.5%. Several studies suggested that efficacy was higher in patients with mild-to-moderate ED and with repeated administration of 100 U doses. The treatment exhibited a favorable safety profile. The most common adverse event was mild, transient penile pain (reported incidence 1.5–6%). No studies reported serious systemic adverse events. The overall strength of the evidence was limited by significant heterogeneity among the included studies and their generally small sample sizes. Conclusions: Based on this systematic review, intracavernosal onabotulinumtoxinA (BoNT-A) may be a beneficial therapeutic option for patients with refractory ED, offering potential improvements in sexual function while reducing the need for invasive therapies. Future large-scale, placebo-controlled studies are essential to confirm these benefits and standardize their clinical application. Full article