Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, underscoring the need for effective therapies. Although miR-125b-5p shows therapeutic potential, its efficacy in metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC and the underlying mechanisms remain unclear. In this study, we aimed to develop a magnetic resonance imaging (MRI)-trackable miR-125b-5p-engineered MSC platform for HCC therapy and to determine whether MASLD attenuates its antitumor efficacy through metabolic reprogramming.

Bone marrow mesenchymal stem cells (MSCs) were genetically engineered to coexpress miR-125b-5p (a therapeutic gene) and ferritin heavy chain (Fth; a MRI reporter gene), enabling sustained delivery and real-time tracking. Orthotopic HCC models with or without MASLD were established to evaluate therapeutic outcomes. In vivo MRI, histological analyses, and bioinformatics approaches were used to assess efficacy and mechanisms.

Transplantation of miR-125b-5p-Fth-MSCs significantly suppressed HCC growth in vivo over an extended period. However, MASLD attenuated this therapeutic effect. Mechanistically, miR-125b-5p directly targeted hexokinase 2 (HK2), inhibiting HCC proliferation and migration through suppression of the PI3K/AKT/mTOR pathway. Fatty acid-induced lipotoxicity upregulated HK2 expression and counteracted the antitumor effects of miR-125b-5p.

Multigene-modified MSCs enable effective, MRI-monitored HCC therapy. MASLD diminishes the efficacy of miR-125b-5p through HK2 upregulation. These findings establish a multimodal theranostic framework for HCC and provide mechanistic insights into MASLD-associated therapeutic resistance.

Hepatocellular carcinoma (HCC) is one of the most prevalent and aggressive malignant tumors globally, with a notably low five-year survival rate. Its high mortality is largely attributed to challenges in early detection. Extracellular vesicles (EVs) are naturally occurring nanoparticles secreted by nearly all cell types and carry a diverse array of bioactive molecules, including proteins, nucleic acids (particularly non-coding RNAs), and lipids. EVs play pivotal roles in remodeling the tumor microenvironment and driving cancer progression through intercellular communication. Accumulating evidence has established that EVs are critically involved in the pathogenesis of HCC and are emerging as promising biomarkers for its early detection. With advances in EV isolation technologies, these vesicles have garnered considerable attention in the field of liquid biopsy for HCC. This review provides a comprehensive overview of the diagnostic potential of EV-derived biomarkers in HCC, including DNA, RNA, proteins, and lipids. Additionally, it discusses the advantages of integrating multi-omics approaches for HCC diagnosis. Furthermore, the review highlights the technical challenges in EV isolation and characterization, as well as the crucial role of reference genes in the standardization of EV data. These insights underscore the potential of EVs as novel, minimally invasive liquid biopsy biomarkers for the early diagnosis of HCC.

Hepatic myelopathy, a rare neurological complication of decompensated chronic liver disease, profoundly impairs quality of life. While liver transplantation represents the only curative treatment for hepatic myelopathy, we report a case in which progressive and severe spastic paraparesis was markedly improved following embolization of a paraspinal vein shunt.

Chaperone-like proteins are involved in the pathogenesis of coronavirus infection through regulation of the viral life cycle, immune response, and antigen presentation. A recently discovered class of chaperones, called heat-resistant obscure proteins (Hero proteins), performs functions similar to other molecular chaperones. This study aimed to investigate the association between the gene encoding the Hero protein SERF2 (Hero7) and the risk of severe COVID-19.

This case-control study was conducted according to the STROBE protocol. A total of 1,373 unrelated Russians (178 patients with severe COVID-19 and 1,195 controls) were recruited. Genotyping of rs4644832 in the SERF2 gene was performed using a probe-based polymerase chain reaction approach. The effects of the single nucleotide polymorphisms (SNPs) were analyzed using bioinformatics tools, including GTExPortal, eQTLGen, HaploReg, atSNP, Gene Ontology, Lung Disease and Common Metabolic Diseases Knowledge Portals, and the STRING database.

SNP rs4644832 in the SERF2 gene (effect allele G) was associated with a decreased risk of severe COVID-19 in the total sample (odds ratio (OR) = 0.56, 95% confidence interval (CI) 0.39–0.81, P = 0.001), females (OR = 0.51, 95% CI 0.31–0.87, P = 0.006), non-smokers (OR = 0.46, 95% CI 0.29–0.74, P = 0.0004), individuals with body mass index ≥ 25 (OR = 0.42, 95% CI 0.25–0.7, P = 0.0004), individuals with low fruit and vegetable intake (OR = 0.38, 95% CI 0.22–0.67, P = 0.0004), and individuals with low physical activity (OR = 0.41, 95% CI 0.23–0.75, P = 0.002).

The G allele of rs4644832 in the SERF2 gene appears to have a protective effect against severe COVID-19. Functional annotation of rs4644832 suggests that it may influence COVID-19 pathogenesis through regulation of proteostasis, ubiquitination, inflammation-induced protein aggregation, the viral life cycle, and cytoskeletal functions.

End-stage liver disease (ESLD) is characterized by a dramatic deterioration of liver function, frequently accompanied by systemic inflammatory storms and multiple organ failures. Central to the onset and progression of ESLD, systemic inflammation arises from complex interactions among various inflammatory signaling molecules and immune cells within and beyond the liver. As key inflammatory modulatory molecules, bioactive oxylipins have been increasingly recognized for their complex molecular mechanisms implicated in various diseases. This review aims to summarize recent findings regarding the molecular and immunological mechanisms through which oxylipins contribute to the development of liver injury and failure, with emphasis on both substantial intrahepatic and extrahepatic immune and inflammatory dysregulation associated with ESLD. Furthermore, this review discusses the translational potential of targeting oxylipins for clinical diagnosis, prognosis, and therapeutic intervention in ESLD.

Metabolic dysfunction–associated steatotic liver disease (MASLD), defined by the American Association for the Study of Liver Diseases as hepatic steatosis with at least one cardiometabolic risk factor, affects approximately 30–40% of adults worldwide. This condition may progress to fibrosis, cirrhosis, and hepatocellular carcinoma. The rising prevalence, alongside obesity and type 2 diabetes, underscores the need for early risk stratification and integrated therapeutic strategies. Circadian homeostasis, orchestrated by the suprachiasmatic nucleus and core clock gene feedback loops, synchronizes hepatic metabolic pathways with environmental light–dark cycles. The objective of this review is to evaluate the role of circadian disruption and metabolic dysfunction in the development of hepatic steatosis, as well as to assess current and potential treatment modalities for both disorders. Circadian disruption through shift work, artificial light at night, sleep restriction, and chrono-nutritional misalignment destabilizes hepatic clocks, promoting insulin resistance, dyslipidemia, inflammation, and steatosis. Experimental models demonstrate that clock gene dysfunction alone can induce steatohepatitis, while progressive MASLD further impairs central circadian regulation, establishing a self-reinforcing chrono-metabolic cycle. Pharmacologic therapies, including glucagon-like peptide-1 receptor agonists and thyroid hormone receptor-β agonists, improve histologic endpoints and fibrosis regression, although heterogeneity among clinical trials precludes direct comparison. Recent evidence characterizing MASLD as a predominantly nocturnal metabolic disorder further highlights persistent nighttime insulin dysregulation despite weight loss, emphasizing the potential role of circadian-targeted interventions such as melatonin. In conclusion, the peripheral circadian clock is intricately linked with MASLD pathogenesis, and metabolic dysfunction, in turn, disrupts circadian pathways. Several pharmacologic therapies offer potential for the treatment of MASLD and circadian dysfunction.

Hepatic iron deposition (HID) in the reticuloendothelial system (RES) is associated with histological severity in metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to assess the interaction between the transferrin (TF)-rs1049296 C>T variant and HID patterns on the risk of significant liver fibrosis in MASLD.

We analyzed 406 adults with liver biopsy-confirmed MASLD. HID was categorized as hepatocellular, RES, or mixed, based on Perl's iron staining. The association between iron-related genetic variants and significant liver fibrosis (fibrosis stage ≥ F2) was analyzed, focusing on the interactions between single-nucleotide polymorphism genotypes and iron deposition patterns. Multivariable logistic regression analysis was used to adjust for potential confounders.

HID was detected in 271 (66.7%) patients, with hepatocellular, RES, and mixed patterns accounting for 11.1%, 18.0%, and 37.7%, respectively. A significant interaction was observed between HID and the TF-rs1049296 genotype (P = 0.035 for interaction). In multivariable analysis, male sex, hypertension, severe lobular inflammation, and mixed hepatocellular/RES iron deposition were independent predictors of significant liver fibrosis. RES deposition markedly increased the risk of significant liver fibrosis (adjusted odds ratio: 6.65; 95% confidence interval: 1.84–23.97, p < 0.05), particularly in men with isolated RES iron deposition (adjusted odds ratio: 5.26; 95% confidence interval: 1.21–22.81, p < 0.05).

The TF-rs1049296 T allele interacts with RES iron deposition to identify a MASLD subpopulation at elevated risk of progressive liver disease, providing opportunities for refined risk stratification and personalized management.

Microbial resistance and oxidative stress are two significant health issues associated with chronic illnesses and therapy failures. The antioxidant and antibacterial properties of Euphorbia cuneata Vahl. aerial component extracts made with various polarity solvents were assessed in this work.

Disc diffusion and minimum inhibitory concentration (MIC) tests were used to evaluate the 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity, total phenolic and flavonoid contents, and antimicrobial activity of n-hexane, toluene, ethanolic, and aqueous extracts against specific ESKAPE pathogens (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans). High-performance liquid chromatography and gas chromatography-mass spectrometry were used to further characterize the most active extract.

Compared to the aqueous (IC₅₀ = 51.61 µg/mL), toluene (IC₅₀ = 30.57 µg/mL), and n-hexane (IC₅₀ = 128.15 µg/mL) extracts, the ethanolic extract demonstrated the greatest 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity (97.90 ± 0.8%; IC₅₀ = 28.52 µg/mL). Additionally, it has the highest levels of flavonoids (40.5 ± 1.5 mg luteolin equivalents/g) and phenolic (80.0 ± 0.2 mg gallic acid equivalents/g). While gas chromatography-mass spectrometry found methyl 12-hydroxy-9-octadecenoate (44.39%) as the main volatile molecule, high-performance liquid chromatography analysis identified caffeic acid, pyrogallol, rutin, and 7-hydroxyflavone as important ingredients. The ethanolic extract showed antifungal activity against C. albicans (MIC = 6.25 mg/mL) and moderate antibacterial activity with the lowest MIC values against S. aureus (450 µg/mL) and E. coli (500 µg/mL).

The ethanolic extract of Euphorbia cuneata demonstrated potent in vitro antioxidant activity and moderate antimicrobial effects, primarily attributable to its high phenolic and flavonoid content. These results support its potential as a natural source of bioactive compounds for further development.