Metabolic dysfunction-associated steatotic liver disease (MASLD) is an independent risk factor for cardiovascular disease (CVD). While gut bacteria have been linked to CVD, the role of intestinal fungi in subclinical coronary atherosclerosis (SCA) remains unclear. In this study, we aimed to investigate the association between the gut mycobiome and SCA in MASLD.

A cross-sectional study was conducted among 103 MASLD patients without established CVD. Fibrosis and steatosis were assessed using magnetic resonance elastography (MRE) and proton density fat fraction, respectively. SCA was defined by coronary artery calcification (CAC). Fecal fungal composition was analyzed via internal transcribed spacer sequencing.

Mean age was 60.8 ± 11.2 years; 51.5% were men; 20.4% had cirrhosis. CAC correlated with MRE (r = 0.489, p < 0.001), interleukin-6 (r = 0.407, p < 0.001), and tumor necrosis factor-α (r = 0.254, p = 0.018), but not proton density fat fraction. Cirrhosis patients had higher CAC than F0–F3 (456.9 vs. 205.9, p = 0.033). Candida albicans (C. albicans) abundance was greater in cirrhosis and correlated with CAC (r = 0.403, p < 0.001) and MRE (r = 0.212, p = 0.032). In multivariate analysis, older age, diabetes, obesity, cirrhosis, and enriched C. albicans independently predicted CAC ≥ 100 AU in MASLD.

In MASLD, cirrhosis and C. albicans enrichment are independently associated with higher SCA burden, suggesting advanced liver disease and a potential fungal contribution to CVD pathogenesis.

Thalassemia is a group of anemias that result from inherited defects in the production of the beta chain of hemoglobin. It is stabilized by gamma globin, which combines to form fetal hemoglobin. One therapeutic approach is to target histone deacetylase (HDAC), which plays an important role in controlling beta thalassemia. This study sought to identify a natural inducer for treating this disease.

Twenty-five Andrographis paniculata compounds were screened using Schrödinger Suite 2020 (Maestro 12.3) for ligand preparation, grid generation, glide extra precision docking and molecular mechanics/generalized born surface area scoring. The HDAC2 crystal structure (Protein Data Bank ID: 4LXZ) was prepared by removing crystallographic water molecules and performing restrained minimization. Top-scoring complexes were subjected to 5-ns molecular dynamics simulations in GROMACS 2019 using the optimized potentials for liquid simulations force field, three interaction site point charge solvation, and standard neutralization and equilibration protocols. Absorption, distribution, metabolism, and excretion properties were predicted using QikProp.

Among the twenty five screened compounds, SRJ09 derivative of andrographolide, ranked among the top candidates based on glide extra precision docking and molecular mechanics/generalized born surface area scores and was therefore selected for further analysis. SRJ09 showed favorable binding to the HDAC2 active site, with interactions comparable to the reference inhibitor 20Y. Absorption, distribution, metabolism, and excretion predictions indicated acceptable drug-likeness, and molecular dynamics simulations demonstrated stable SRJ09–HDAC2 complex behavior over 5 ns.

We concluded that beta thalassemia may benefit from the use of andrographolide, and SRJ 09 as prospective HDAC2 inhibitor drugs that are favourable and efficacious and that generate fetal hemoglobin. Therefore, this bioactive compound is worth further investigation using in vitro and in vivo studies.

This narrative review provides a detailed and comprehensive examination of hemoadsorption therapy and its role in treating severe poisoning. First, the global problem of suicidal and nonsuicidal self-injury is described, with regional differences in the types of poisons used noted. Lower- and middle-income countries are disproportionately affected by pesticides compared to high-income countries. Organophosphates often constitute the majority of pesticide poisoning in many of these countries. Next, we review the history of hemoadsorption therapy from its early origins to its current evolution. The key physical and chemical principles underlying extracorporeal therapy and its effectiveness are described. A review of the literature examining the evidence for the efficacy of hemoadsorption therapy in poisoning is presented. Current evidence-based guidelines are summarized, including toxin types, clinical indications, and the extracorporeal therapies recommended. Emerging evidence regarding the use of hemoadsorption therapy for severe organophosphate and calcium channel blocker poisoning is also considered. A care pathway for considering hemoadsorption in poisonings where formal guidelines are lacking is proposed. Both the hemoadsorption strategies used and the potential adverse effects of this therapy are discussed. For this narrative review, the PubMed/Medline was searched from inception to April 30, 2025, using the terms (“hemoperfusion” OR “hemadsorption”) AND (“poisoning”). Clinical trials, randomized controlled trials, and meta-analyses were included, along with additional relevant studies identified through a manual review of references. The role of modern resin bead hemoadsorption therapy for severe poisoning is expanding to include removal of commonly encountered poisons that are protein-bound and have a large volume of distribution. Using a multicycle approach, hemoadsorption therapy has shown improved outcomes for both calcium channel blockers and organophosphate poisoning.

Cardiorenal syndrome is associated with high morbidity and mortality and is characterized by bidirectional interactions between cardiac and renal dysfunction. The advent of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the nonsteroidal mineralocorticoid receptor antagonist finerenone has substantially changed the therapeutic landscape. Combination therapy with SGLT2i and finerenone may provide additional benefits through complementary mechanisms, representing a potential paradigm shift in the management of cardiorenal syndrome. In this review, we examine the pathophysiological pathways that characterize cardiorenal syndrome, clinical data from major randomized controlled trials, and the rationale for the concomitant use of these two drug classes. SGLT2 inhibitors significantly reduce hospitalization for heart failure, slow renal function decline, and provide benefits in both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction, irrespective of diabetes status. Finerenone has been shown to reduce the risk of cardiovascular events and chronic kidney disease progression in patients with type 2 diabetes and chronic kidney disease, with a more favorable safety profile than steroidal mineralocorticoid receptor antagonists. Emerging evidence suggests that combination therapy may reduce hospitalizations for heart failure and slow renal disease progression beyond the effects of either monotherapy. However, implementation of these therapeutic options requires careful patient selection, ongoing monitoring of renal function and electrolytes, and close collaboration between cardiologists and nephrologists.

Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence and mortality rates worldwide, in which immune evasion mechanisms play a crucial role in its progression and treatment. Natural killer group 2D ligands (NKG2DL), as key molecules activating immune cells, significantly influence the immune evasion of liver cancer through their regulatory mechanisms. This review summarizes the regulatory mechanisms of NKG2DL expression, including genetic, signaling pathway, non-coding RNA, and stress response modulation, and discusses their expression patterns and clinical relevance in HCC. Studies have shown that the expression status of NKG2DL not only impacts patient prognosis and therapeutic response but also provides potential targets for HCC immunotherapy. Future research should focus on the molecular networks regulating their expression and their synergy with immunotherapy to provide a theoretical basis for developing more precise diagnostic and personalized treatment strategies for HCC.

Combined traumatic brain injury (CTBI) remains a leading cause of disability/mortality among workers, yet which routine biochemical tests that predict infectious complications remain controversial. We aimed to identify the most informative serum markers for early diagnosis and prognosis of such complications.

In this retrospective observational study, 80 acute CTBI patients (40 without vs. 40 with mainly bacterial infectious complications) and 40 healthy controls were analyzed. Serum collected at 24, 72, and 168 h was assayed for protein fractions, metabolic markers, lipid peroxidation indices, antioxidant activity, endogenous intoxication markers, acids/minerals, and relevant enzymes.

The study found that the most important prognostic indicator for infectious complications was a simultaneous increase in α1-globulins, β-globulins, diene conjugates, superoxide dismutase, medium- and low-molecular-weight substances in erythrocytes, erythrocyte oligopeptides, and lactate at 24 h after injury (p < 0.001). A significant increase in sialic acids, uronic acids, total Ca and P, and low-density lipoproteins was observed at 72 h after injury (p < 0.001). Notably, individual components from the 24-h panel demonstrated high standalone predictive value, with areas under the curve of diene conjugates (0.91), erythrocyte oligopeptides (0.87), β-globulin (0.86), α1-globulin (0.82), and superoxide dismutase (0.82), respectively. The elevation of these biomarker profiles was significantly correlated with worse clinical outcomes, including longer intensive care unit stay and ventilation duration.

This study identified a set of biochemical markers associated with infectious complications in patients with CTBI. These biochemical parameters may serve as additional diagnostic and prognostic criteria for the management of infectious complications in patients with СTBI.

Luteolin is a dietary flavonoid widely distributed in fruits and vegetables. It has attracted substantial preclinical interest due to its pleiotropic hepatoprotective effects against hepatic steatosis, inflammation, fibrosis, and hepatocellular carcinoma. By reviewing data from in vitro and in vivo studies, this review comprehensively synthesizes the full spectrum of liver-directed pharmacology of luteolin, covering metabolic and toxic liver injury, fibrosis, cancer, and viral hepatitis, while critically mapping each mechanism to specific disease contexts and systematically identifying the key challenges limiting its clinical translation. The underlying mechanisms of luteolin action involve activation of Nrf2-mediated antioxidant defense, suppression of NF-κB- and NLRP3-driven inflammatory responses, inhibition of hepatic stellate cell activation via the TGF-β/Smad and STAT3 pathways, and regulation of metabolic homeostasis through liver X receptor (LXR)/SREBP-1c and AMPK signaling. Despite well-characterized mechanisms in preclinical models, several critical gaps hinder its clinical translation: (1) Rigorous randomized controlled trials in well-defined patient populations are scarce, with only one combination supplement study reported. (2) The relative contribution of luteolin metabolites to its overall bioactivity remains poorly understood, even though derivatives such as luteolin-7-diglucuronide exhibit distinct pharmacological properties. Cell-type-specific delivery systems, which show promise in preclinical fibrosis and cancer models, have not been evaluated clinically. (3) Systematic studies on the synergistic effects of luteolin with standard-of-care drugs remain largely exploratory. Overall, luteolin is a promising multi-target nutraceutical for liver diseases, and its clinical translation requires optimized delivery strategies, investigation of metabolite activity, and well-designed human clinical trials.

The pathogenic role of MIR142 genetic abnormalities in the development of primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) is unexplored. The objective of this study was to investigate the frequency, spectrum, and functional significance of mutations in the MIR142 gene in primary CNS DLBCL.

Direct Sanger sequencing of the MIR142 gene was performed in tumor tissue from 35 patients with primary DLBCL of the CNS. In silico prediction of microRNA (miRNA)–target interactions, enrichment analysis of target gene ontologies, and prediction of the secondary structure and minimum free energy of the miRNA hairpin were performed.

The mutation frequency was 37.1% (95% confidence interval: 23.2–53.7%). The vast majority of the identified single-nucleotide variants were located outside the regions encoding mature miRNA chains. In silico analysis showed that the n.29A>G mutation located in the seed sequence of miR-142-5p resulted in a significant reduction in the number of potential targets and alterations to the interaction spectrum. All single-nucleotide variants identified in the study patients caused a change in minimum free energy and affected the shape and length of the hairpin stem of pri-miRNA. The results indicate the fragility of the pri-miR-142 hairpin.

The frequency of gene mutations in primary DLBCL of the CNS significantly exceeds that reported for systemic DLBCL.

Immunothrombosis, the interplay between immune activation and coagulation, contributes to disease progression in inflammatory disorders. Its role in hepatitis B virus–related acute-on-chronic liver failure (HBV-ACLF) and the involvement of neutrophil extracellular traps (NETs) remain unclear. This study aimed to elucidate NETs-mediated immunothrombosis in HBV-ACLF.

Liver single-cell RNA sequencing data from HBV-ACLF patients and healthy controls were analyzed to define immune and endothelial transcriptional profiles. A cohort of 46 HBV-ACLF patients, 20 chronic hepatitis B patients, and 20 healthy controls was assessed for circulating NETs, endothelial injury markers, and coagulation parameters. Histopathology and in vitro assays examined NETs distribution and endothelial interactions.

NETs were markedly elevated in HBV-ACLF and correlated with endothelial injury markers (syndecan-1, von Willebrand factor, soluble thrombomodulin), coagulopathy, and prognostic scores. Histology revealed NETs colocalization with endothelial cells and platelets within hepatic microthrombi. NETs from patient neutrophils impaired endothelial integrity and enhanced procoagulant activity in vitro. Mechanistically, toll-like receptor 2 (TLR2) and complement component 5a receptor 1 (C5aR1) signaling were involved in NETs formation, and their pharmacological inhibition reduced NETs generation.

NETs are associated with endothelial injury and immunothrombosis in HBV-ACLF. Mechanistic analyses suggest a role for TLR2 and C5aR1 pathways in NETs formation, indicating potential targets for future therapeutic investigation.