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.

Pancreatic cystic neoplasms (PCNs) are increasingly detected in clinical practice, yet substantial variability exists in imaging interpretation and reporting, which may affect clinical decision-making. This guideline was developed to standardize diagnostic imaging evaluation and reporting for PCNs. A multidisciplinary expert panel conducted literature search and critical appraisal of domestic and international evidence, identified key clinical questions, and formulated recommendations using the Grading of Recommendations Assessment, Development and Evaluation framework. A modified Delphi consensus process and external review were performed to ensure the robustness of the recommendations. A total of 21 key questions were addressed, covering essential aspects of imaging evaluation and reporting for PCNs, including the preferred imaging modality for suspected lesions; standardized measurement of cyst size and mural nodules and their clinical significance; definitions of cyst wall and septal thickening; optimal imaging approaches for assessing the relationship between cystic lesions and the main pancreatic duct; measurement and evaluation of main pancreatic duct diameter and dilation; imaging-based classification of intraductal papillary mucinous neoplasms and serous cystic neoplasms; assessment of ductal obstruction, calcification, hemorrhage, and pancreatitis-related changes; criteria for suspicious lymph nodes; differentiation of PCNs from pancreatic pseudocysts or retention cysts; and recommended imaging modalities and follow-up intervals. This guideline provides a structured and evidence-based framework for imaging evaluation and reporting of PCNs, which may improve the consistency and clarity of imaging reports and support clinical decision-making.

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.

Antralization is considered a critical, reversible stage preceding gastric cancer. However, available biomarkers for identifying antralization are lacking. This study aimed to explore antralization-specific biomarkers in peripheral blood and gastric mucosa.

In this prospective cohort study, adult patients presenting with upper gastrointestinal symptoms were enrolled and categorized into antralization and non-antralization groups based on pathological examination of gastric mucosa. Helicobacter pylori (H. pylori) infection was detected using the 13C-urea breath test, rapid urease test, and/or H. pylori serological test. Blood samples and gastric biopsies were collected for biomarker analysis.

Of the 92 patients studied, 42 (45.7%) were diagnosed with H. pylori infection and 61 (66.3%) with antralization. The rate of H. pylori infection and the incidence of acid reflux were higher in the antralization group than in the non-antralization group (both P < 0.05). Patients with antralization had higher plasma lymphocyte counts and lower serum levels of lipopolysaccharide (both P < 0.05). The positive rates and intensity of trefoil factor-2 and mucin (MUC) 6 expression were higher, whereas the positive rate and intensity of MUC5AC expression were lower in the incisura and body mucosa with antralization compared with those without antralization (all P < 0.05). Additionally, the intensity of MUC5B expression was higher in the gastric body mucosa with antralization than in those without antralization (P < 0.05).

Increased lymphocyte counts and decreased lipopolysaccharide levels in the blood, along with increased expression of trefoil factor-2, MUC6, and MUC5B and decreased MUC5AC expression in the proximal gastric mucosa, appear to be antralization-specific.

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.

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.

Preclinical studies of the serotonin 2A (5-HT2A) antagonist deramciclane suggested an anxiolytic profile, which has not been unequivocally established in the clinic. The same receptor profile also indicated that the compound may exhibit antidepressant potential. However, evidence for these effects remains inconclusive. The present study examined the effect of the drug in two preclinical tests with predictive validity for antidepressant activity.

The antidepressant-like activity of deramciclane was assessed in male Sprague-Dawley rats by measuring immobility time in the forced swim test (doses: 1, 5 mg/kg) and ambulation scores in the bilateral olfactory bulbectomized (doses: 5, 10 mg/kg) rat model. In both tests, the clinically effective antidepressant imipramine served as the control condition.

In the forced swim test, there was a statistically significant effect of treatment on immobility time (F2,34 = 5.77; p < 0.01; analysis of variance), which was attributable to the effect of the 5 mg/kg dose (p < 0.01; Bonferroni post-hoc test). Deramciclane at 1 mg/kg was not significantly different from vehicle-treated animals. By contrast, neither dose of deramciclane (5 mg/kg or 10 mg/kg) reversed the hyperactivity of olfactory bulbectomized rats, whereas imipramine was active in both tests.

Deramciclane demonstrates contradictory evidence for antidepressant-like activity in two validated pharmacological tools that identify such potential. The agent is clearly active in the forced swim test but not in the bulbectomized rat model. Further evaluation of the antidepressant-like potential of deramciclane in pharmacological models with predictive validity is warranted, and a more detailed examination of the dose-response relationship may be informative.