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.

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.

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.

For individuals with decompensated advanced chronic liver disease (dACLD), the onset of refractory ascites (RA) represents a dramatic event. In this setting, a relevant proportion of RA patients develop kidney dysfunction, as well as hepatorenal syndrome-acute kidney injury, with limited therapeutic and survival chances. An 81-year-old woman with dACLD-RA was admitted with severe ascites and stage IV chronic kidney dysfunction. On the second day, hepatorenal syndrome-acute kidney injury occurred, requiring standard medical therapy. Intravenous human albumin (HA) and terlipressin administration were compromised by poor venous access and severe respiratory dysfunction. After excluding transjugular intrahepatic portosystemic shunt and transplantation due to age and comorbidities, peritoneal dialysis (PD) was initiated, leading to renal recovery and ascites resolution. Two weeks later, she was readmitted due to the unfeasibility of accessing peripheral veins for the intravenous administration of HA, which was essential to support circulatory function, preserve oncotic balance, and properly manage both RA and chronic kidney dysfunction. A novel PD+HA protocol was therefore started, with intraperitoneal infusion of HA-enriched dialysate to allow a positive albumin gradient from dialysate to blood. Over 12 months, serum albumin levels increased, and clinical stability and improved nutritional status were observed, with no additional hospitalizations or complications. This is the first case describing the application of HA-enriched PD in managing a dACLD patient with RA and kidney dysfunction. HA-enriched PD may represent a promising strategy in complex dACLD care by guaranteeing frequent and small-volume paracentesis and preservation of oncotic pressure without dialytic albumin loss.

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.

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.

The prognostic nutritional index (PNI), calculated from serum albumin and lymphocyte count, reflects a patient’s immune-nutritional status and has been proposed as a prognostic marker in hepatocellular carcinoma (HCC). However, its role in advanced HCC patients treated with atezolizumab plus bevacizumab (Ate/Bev) remains unclear. In this study, we aimed to evaluate the prognostic value of PNI in patients receiving first-line Ate/Bev therapy.

We retrospectively analyzed 362 patients with unresectable HCC who received Ate/Bev between November 2020 and June 2023 across two centers. Based on prior literature, a cutoff of 45 was used to classify patients into low-PNI (<45) and high-PNI (≥45) groups. Propensity score matching was performed to balance baseline characteristics.

After propensity score matching, 130 patients (65 per group) were included in the analysis. The high-PNI group showed a significantly lower incidence of grade ≥ 3 treatment-related adverse events (10.8% vs. 24.6%, p = 0.039), a higher objective response rate (38.4% vs. 20.0%, p = 0.037), and significantly longer overall survival (16.7 vs. 7.9 months, p = 0.009). Although progression-free survival was longer in the high-PNI group (4.8 vs. 3.0 months), the difference was not statistically significant (p = 0.597). Multivariate analysis confirmed that PNI was an independent predictor of overall survival (hazard ratio: 0.574, 95% confidence interval: 0.353–0.933, p = 0.025), after adjusting for vascular invasion, alpha-fetoprotein levels, concurrent therapy, and post-treatment interventions.

PNI is an independent prognostic factor for overall survival in advanced HCC patients treated with Ate/Bev in real-world clinical practice. Incorporating PNI into routine assessments may enhance risk stratification and guide therapeutic decision-making.

Pancreatic fibrosis, a major pathological feature of chronic pancreatitis, is primarily driven by the abnormal activation of pancreatic stellate cells (PSCs) and excessive deposition of extracellular matrix. Traditional Chinese medicine (TCM) offers a holistic and synergistic approach to preventing and treating pancreatic fibrosis through multi-target regulation of PSC activation. This review systematically elucidates the mechanisms by which TCM—encompassing both bioactive monomers and compound formulations—modulates key signaling pathways involved in PSC activation, including the mitogen-activated protein kinase, transforming growth factor-β/Smad, platelet-derived growth factor, nuclear factor kappa B, and Wingless/β-catenin pathways. By simultaneously targeting these interconnected signaling networks, TCM strategies effectively inhibit PSC activation, attenuate inflammatory responses, and reduce extracellular matrix deposition. In contrast to single-target pharmacological inhibitors, TCM embodies a “multi-component, multi-pathway” therapeutic paradigm that aligns with the complex pathophysiology of pancreatic fibrosis. This review also draws comparative insights from liver fibrosis, highlighting conserved pathways and organ-specific regulatory contexts. Ultimately, TCM represents a promising integrative avenue for the prevention and treatment of pancreatic fibrosis, supported by growing preclinical evidence and aligned with the principles of holistic intervention.