Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the third leading cause of cancer-related death. Hyperactivation of oncogenes and suppression of tumor suppressor genes/proteins drive HCC initiation and progression. MicroRNAs (miRNAs) critically modulate HCC biology by regulating proliferation, apoptosis, and metastasis. Acting either as tumor suppressors or oncomiRs, they shape core signaling pathways, including PI3K/Akt/mTOR, Hippo–YAP/TAZ, Wnt/β-catenin, RAS/MAPK, and p53. Their dysregulation in tissues and body fluids renders them promising diagnostic biomarkers and therapeutic targets. Preclinical studies demonstrate that miRNA-based strategies—either restoring tumor-suppressive miRNAs (e.g., miR-34a, miR-125a-5p) or inhibiting oncogenic miRNAs (e.g., miR-660-5p)—can suppress HCC progression and reduce treatment resistance. Combination approaches, such as pairing miR-122 mimics with miR-221 inhibitors or delivering miR-326 via nanoparticles, further enhance efficacy by simultaneously targeting multiple oncogenic pathways. This review summarizes recent advances in miRNA-mediated regulation of HCC signaling and highlights their clinical potential, including ongoing trials of miRNA-based diagnostics and therapeutics for early detection, prognostication, and personalized treatment.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly increasing and is caused by excessive fat deposition in the liver due to non-alcoholic factors. Aging is a major risk factor for the development and progression of MASLD. In this study, we investigated the metabolic effects of tilorone, a synthetic small molecule, in a high-fat diet (HFD) mouse model, with a focus on the liver function and signaling. We demonstrate that tilorone attenuated HFD-induced steatosis by restoring bone morphogenetic protein 9 (BMP9)-Smad1/5/8 signaling and upregulating peroxisome proliferator-activated receptor gamma (PPARγ) expression. Tilorone reduced HFD-induced increases in body weight, adipose tissue and liver weight, and blood glucose levels, and improved glucose tolerance in HFD mice. PET/MRI imaging demonstrated enhanced ¹⁸ FDG ( ¹⁸ F-fluoro-2-deoxyglucose) uptake in liver, skeletal muscle, adipose tissue, and myocardium of tilorone-treated HFD animals. Histological analysis showed that tilorone reduced the HFD-induced diffuse, macrovesicular steatosis (S3/3), and machine learning-based image analysis revealed a decrease in lipid droplet size and lipid content. HFD caused the disappearance of liver glycogen, but tilorone increased glycogen levels. High-resolution respirometry indicated that tilorone reduced HFD-induced increases in mitochondrial complex II-linked oxidative phosphorylation and complex IV activity. These findings revealed the beneficial effects of tilorone on HFD and highlight its therapeutic potential in MASLD, particularly given that tilorone is a synthetic small molecule and can be administered orally. Further studies are required to explore its clinical application.

Background: Wilson’s disease (WD) is a genetic disorder of copper metabolism with over 600 disease-causing mutations, leading to variable hepatic and neurological symptoms. Early diagnosis and treatment are crucial. To evaluate hepatic involvement, serum scores and non-invasive imaging techniques complement histology. Methods: This pilot study assessed the utility of ultrasound-based tissue attenuation imaging (TAI), tissue scatter distribution imaging (TSI), and shear-wave elastography (SWE) for quantifying steatosis and fibrosis in WD. Results: Among 131 treated patients, 53 (mean age 40.5 ± 13.1 years, M/F = 35/18) underwent measurements. Based on literature-validated thresholds, 41 patients did not have significant liver fibrosis, 5 patients had moderate (F2) and 4 advanced (F3) fibrosis, while 3 patients had cirrhosis. The LS (liver stiffness) was in moderate correlation with FIB-4 (r = 0.306, p < 0.03), NAFLD fibrosis index (r = 0.336, p < 0.02), and APRI (r = 0.31, p = 0.0857). Among the WD patients, 37 had no steatosis (S0), 14 had mild steatosis (S1), and 2 had intermediate steatosis (S2); none of them had severe steatosis (S3) based on UEFF calculation. LS correlated positively with calculated free copper and negatively with serum ceruloplasmin. Normal-BMI patients exhibited no significant steatosis (R2 = 0. 0065, p = 0.966) by ultrasound-estimated fat fraction (UEFF), while those with BMI > 25 kg/m² had increased UEFF correlating with BMI (R2 = 0.288, p < 0.015). Over a five-year follow-up using liver elastography, the fibrosis score did not progress significantly in adequately treated patients. Conclusions: Ultrasound with artificial intelligence-derived parameters supports the non-invasive evaluation of hepatic steatosis and fibrosis in WD, complementing clinical and laboratory data. However, population-specific liver stiffness thresholds are still needed.

Background: Interdigitating dendritic cell sarcoma (IDCS) is a very rare haematologic malignant tumour that arises from antigen-presenting cells. While it primarily affects the lymph nodes, extranodal manifestations have been observed, and there is a slight male predominance. Due to its rarity, diagnosing IDCS can be challenging, as illustrated in our case report of a 61-year-old woman. Methods: In this case presentation, the oncological management of a patient suspected of having malignant melanoma metastasis in the neck lymph nodes is discussed. This includes otorhinolaryngological examinations, fine needle aspiration biopsy, PET CT imaging, and histological analysis with immunohistochemistry. Results: The patient’s medical history included the excision of a pigmented lesion from the left ala of her nose, which was diagnosed as malignant melanoma. After surgical treatment, she experienced a tumour-free period of one year; however, during a follow-up ultrasonography three pathological lymph nodes were detected on the left side of her neck. Initially, a nodal metastasis of melanoma was suspected. Yet, fine needle aspiration cytology revealed myofibroblastic tumour invasion, and a re-biopsy showed no signs of malignancy. To further investigate, PET-CT scans were conducted, and a modified radical neck dissection was performed based on the findings. The histological analysis of the lymph nodes revealed an IDCS, a second independent tumour distinct from the initially diagnosed malignant melanoma, originating from the submandibular, upper jugular, and mid-jugular lymph nodes. Conclusions: This case highlights the diagnostic difficulties associated with IDCS. Initially, the clinical suspicion of malignant melanoma was considered, necessitating further examinations and a multidisciplinary approach to reach a final diagnosis and provide the patient with appropriate treatment.