Chronic hepatitis B virus (HBV) infection is the leading risk factor for hepatocellular carcinoma (HCC). Lactylation-related genes (LRGs) participate in HCC progression, yet their roles in HBV-associated HCC (HBV-HCC) remain largely unclear. In this study, we screened differentially expressed LRGs (DE-LRGs) from HBV-HCC transcriptomic data using weighted gene co-expression network analysis (WGCNA) and built a high-precision random forest prediction model. Three hub genes (RACGAP1, STMN1, ILF2) were verified to be overexpressed in HBV-HCC tissues across multiple datasets and quantitative real-time polymerase chain reaction (qPCR), and their high expression correlated with unfavorable overall survival and distinct immune infiltration. A three-gene nomogram was constructed in the GSE47197 cohort, with an area under the curve (AUC) of 0.928 validated by calibration curves, decision curve analysis (DCA) and receiver operating characteristic (ROC) curves. External validation in GSE121248 reached an AUC of 0.965, verifying its robust predictive power. Moreover, consensus clustering divided HBV-HCC into two LRG-based molecular subtypes, where Cluster 2 had worse prognosis. Collectively, this study establishes an LRG-based predictive model and identifies two molecular subtypes for HBV-HCC, providing reliable and promising biomarker candidates for HBV-HCC risk prediction and individualized immunotherapy.
This study explores the role and mechanism of RNA m6A methylation in reduced antiplatelet response to aspirin in older adults. A total of 34 patients aged ≥60 years routinely receiving 100 mg/d aspirin were enrolled. Based on light transmission aggregometry (LTA), subjects were divided into a low-response group (n = 14, platelet aggregation rate (PAR) ≥12 %) and a high-response group (n = 20, PAR ≤7 %). Patients with a low aspirin response exhibited higher levels of m6A, accompanied by elevated methyltransferase-like 3 (METTL3) and YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) (p < 0.05). Serum levels of prostaglandin H2 (PGH2) and thromboxane B2 (TXB2) were also elevated in the low-response group. Spearman correlation revealed that PAR and PGH2 were positively correlated with both METTL3 and YTHDF1 mRNA, while TXB2 positively correlated with METTL3 mRNA (p < 0.05), indicating the association of m6A degree with aspirin response. Mechanistically, METTL3 overexpression in MEG-01 cells enhanced megakaryocyte proliferation and upregulated YTHDF1, which subsequently increased the translation efficiency of cyclooxygenase 1 (COX-1) mRNA and elevated COX-1 protein. RNA immunoprecipitation confirmed that YTHDF1 directly bound to COX-1 mRNA in a METTL3-dependent manner. The METTL3/YTHDF1-COX-1 axis may attenuate the antiplatelet efficiency of aspirin by modulating AA metabolism and megakaryocyte function, providing a potential biomarker and target for aspirin low-responsiveness.
This study evaluated the protective effects of Plantago asiatica L. (PAL) extract against acute lower limb ischemia-reperfusion injury (LL-IRI). Network pharmacology and molecular docking identified core targets associated with inflammation, oxidative stress, and apoptosis and indicated stable interactions betweenPAL constituents and these targets. In vivo, PAL improved skeletal muscle pathology and ultrastructural injury in LL-IRI rats, reduced interleukin-1β (IL-1β) and malondialdehyde (MDA) levels, restored superoxide dismutase (SOD) and catalase (CAT) activities and Bcl-2 expression, and suppressed Bax and cleaved Caspase-3. In vitro, PAL promoted the proliferation and migration of lipopolysaccharide (LPS)-injured C2C12 cells, stabilized mitochondrial membrane potential, and modulated apoptosis-related proteins. These findings support the view that PAL protects against LL-IRI by attenuating inflammation and oxidative stress and by regulating apoptosis.
Aicardi-Goutières syndrome type 1 (AGS1) is a rare autosomal recessive inflammatory disorder caused by mutations in TREX1 gene, and is frequently misdiagnosed as congenital or neonatal central nervous system infection because of its overlapping clinical manifestations. We report a 27-day-old male neonate who presented with recurrent fever, a persistent cerebrospinal fluid (CSF) pleocytosis, and poor response to broad-spectrum antimicrobial therapy. Imaging revealed diffuse white matter abnormalities and bilateral basal ganglia calcifications. Extensive microbiological investigations were negative, prompting genetic testing. Whole exome sequencing identified two compound heterozygous variants in TREX1: c.294dup (p.Cys99MetfsTer3) and c.868_885del (p.Pro290_Ala295del), inherited from his mother and father, respectively. Based on the clinical manifestations, neuroimaging findings, and genetic results, a diagnosis of AGS1 was established. Treatment with the Janus kinase inhibitor ruxolitinib reduced the frequency and severity of febrile episodes. However, the patient developed microcephaly, neurodevelopmental delay, and motor impairment in infancy. We reported a rare case of AGS1 associated with two compound heterozygous variants, including c.294dup (p.Cys99MetfsTer3) and c.868_885del (p.Pro290_Ala295del). This case expands the genotypic and phenotypic spectrum of TREX1-associated AGS1 and highlights the importance of considering monogenic interferonopathies in neonates presenting with sterile CSF inflammation, intracranial calcifications, and treatment-refractory fever.
Wound healing is a complex process involving inflammation control, protection against infection, oxidative balance, and tissue regeneration. Honey has attracted considerable attention due to its multifunctional biological activities. In addition to its anti-inflammatory and antioxidant actions, honey exhibits broad antimicrobial activity that helps prevent microbial colonization and biofilm formation, thereby facilitating a favorable environment for healing. It also limits oxidative stress through reactive oxygen species (ROS) scavenging and erythroid 2–related factor 2 (Nrf2) activation, resulting in better control of inflammation and improved tissue repair. However, despite promising experimental and clinical evidence, the clinical translation of honey remains limited by variability in composition, lack of standardization, and methodological weaknesses in existing trials, and robust, well-controlled studies and standardized formulations are therefore essential to confirm efficacy and support its integration into evidence-based wound care. This review summarizes current knowledge on how honey supports wound healing, focusing on its antimicrobial, anti-inflammatory, antioxidant, and immunomodulatory effects. The analysis is based on a literature search of MEDLINE, Google Scholar, Scopus, and Web of Science. Overall, honey reduces pro-inflammatory mediators (e.g., tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, nuclear factor kappa B (NF-κB)) and enhances anti-inflammatory responses such as IL-10 and M2 macrophage activity.
