The activation of adenosine-monophosphate-activated protein kinase (AMPK) by berberine (BBR) benefits various inflammatory diseases. Conversely, high mobility group box-1 (HMGB1), a prototypical damage-associated molecular pattern (DAMP), typically exerts opposing effects. This research aims to investigate the relationship between AMPK and HMGB1, elucidating the functions and underlying mechanisms by which BBR alleviates acute lung injury (ALI) caused by lipopolysaccharide (LPS).

Male C57BL/6J mice were intragastrically administered BBR twice daily for three days with a total of 25 and 100 mg/kg/day. On day four, an intraperitoneal injection of 10 mg/kg LPS was administered, and BBR was given two hours before and six hours after this injection, respectively. Eighteen hours post-LPS administration, lung tissues and serum samples were collected to assess indicators of lung tissue injury, inflammation, oxidative stress, and apoptosis. The relationship between AMPK activation, HMGB1 release, and inflammatory activation was investigated in both mice and RAW264.7 cells using protein expression analysis, AMPK silencing, and exogenous HMGB1 introduction.

Our findings demonstrate that BBR activates AMPK and inhibits HMGB1 expression, translocation, and release in LPS-induced ALI, resulting in reduced histopathological lung injuries, decreased expression of inflammatory cytokine genes, and diminished oxidative stress and apoptosis. Mechanistic studies revealed that BBR decreases extracellular HMGB1 in LPS-stimulated RAW264.7 cells and inhibits HMGB1-stimulated nuclear factor Kappa B (NF-κB) activation. Concurrently, silencing the activation of AMPK by siRNA and compound C reversed the BBR-reduced extracellular HMGB1 level in LPS-stimulated RAW264.7 cells.

Based on these findings, we conclude that BBR effectively inhibits inflammation, oxidative stress, and apoptosis in LPS-induced ALI by modulating the AMPK-HMGB1-NF-κB axis. Consequently, BBR and other AMPK activators may represent promising therapeutic options for managing systemic inflammation and injury during sepsis.

Emerging evidence indicates that Akkermansia muciniphila (A. muciniphila or AKK) regulates host glucose metabolism through multiple pathways. In this study, we examined the therapeutic effects of A. muciniphila on chronic sleep deprivation (CSD)-induced glucose dysregulation and the underlying mechanisms.

A modified multiplatform water environment method was used to generate a mouse model of CSD. The mice were divided into three groups: the control (CON) group (ad libitum sleep), the CSD group (subjected to sleep deprivation), and the CSD+AKK group (CSD mice were supplemented with A. muciniphila at 3 × 10⁸ CFU per mouse, three times per week). After an 8-week intervention, glucose metabolism was assessed. Serum concentrations of lipopolysaccharide (LPS), interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) were measured. The mRNA expression and protein expression of mucin 2 (MUC2) and zonula occludens-1 (ZO-1) in the colon tissue were analyzed. Goblet cells in colon tissues were quantified using Alcian Blue–Periodic Acid-Schiff (AB–PAS) staining. Additionally, changes in gut microbiome diversity and composition among groups were compared.

CSD induced significant glucose intolerance and insulin resistance, evidenced by increased area under the curve (AUC) of the oral glucose tolerance test (OGTT), homeostatic model assessment of insulin resistance (HOMA-IR), and fasting insulin levels compared to the CON group (all p < 0.05). This was accompanied by a marked impairment of the colonic mucosal barrier, characterized by a profound loss of goblet cells and downregulation of key barrier components, MUC2 and ZO-1, at both the mRNA and protein levels (all p < 0.05). Intervention with A. muciniphila significantly ameliorated CSD-induced glucose intolerance, insulin resistance and colonic barrier damage. Furthermore, CSD elevated serum levels of LPS, IL-6, TNF-α, and IL-1β (all p < 0.05), which were effectively mitigated by A. muciniphila intervention. 16S rDNA sequencing confirmed the successful colonization of A. muciniphila, as its absolute abundance was significantly greater in the CSD+AKK group than in the CSD group. In addition, A. muciniphila intervention affected the abundance of Burkholderiales bacterium, Lactococcus garvieae, and other bacterial strains in the intestine.

A. muciniphila supplementation effectively ameliorated CSD-induced glucose intolerance, reduced the serum levels of LPS and proinflammatory cytokines (IL-6, TNF-α, and IL-1β), and restored intestinal barrier integrity by upregulating MUC2 and ZO-1 expression in colon tissues.

Odontogenesis-associated phosphoprotein (Odaph) is essential for tooth development. However, its role in osteoblast function and bone remodeling remains unclear. Recent studies suggest that Odaph may influence bone integrity, particularly in the maxillofacial region, thereby implicating it in craniofacial skeletal disorders. The study is designed to clarify the regulatory roles of Odaph in the proliferation, differentiation, and autophagy of osteoblasts, with particular emphasis on its participation in the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) signaling pathway.

The MC3T3-E1 osteoblast cell line was employed as an in vitro model, and the effects of Odaph overexpression on cell proliferation, differentiation, and migration were assessed via qPCR, Western blotting, CCK-8 assay, EdU staining, alkaline phosphatase (ALP) staining, and Alizarin Red S (ARS) staining. RNA sequencing (RNA-seq) was carried out to screen for differentially expressed genes, and subsequent Kyoto Encyclopedia of Genes and Genomes (KEGG)/GO enrichment analyses were conducted to verify the participation of the AMPK/mTOR signaling pathway. Autophagy was assessed via Western blotting, fluorescence double staining, transmission electron microscopy, and autophagy tandem lentiviral detection. For exploring the function of autophagy in osteogenic differentiation, the autophagy inhibitor 3-MA was used to treat the cells. Furthermore, a mouse model was utilized to confirm the impacts of Odaph overexpression on osteogenesis and autophagy in vivo.

Overexpression of Odaph markedly enhanced the proliferation, migration, and osteogenic differentiation of MC3T3-E1 cells, which was supported by the increased expression of osteogenic markers runt-related transcription factor 2 (RUNX2), Collagen I (COL1), and ALP. RNA-seq analysis demonstrated that genes regulated by Odaph were notably enriched in the AMPK/mTOR signaling pathway. Further validation demonstrated that Odaph increased AMPK phosphorylation while suppressing mTOR activity. Odaph overexpression also enhanced the expression of autophagy-related proteins LC3B-II and BECLIN1 while reducing p62 levels, whereas 3-MA treatment markedly attenuated these pro-osteogenic effects. Consistently, animal experiments confirmed that Odaph overexpression enhanced osteogenesis in vivo, accompanied by increased AMPK activation and autophagy induction.

Odaph enhances osteoblast function through autophagy induction mediated by the AMPK/mTOR axis. These results reveal a new regulatory mechanism in bone biology and indicate that Odaph could serve as a potential therapeutic target for maxillofacial bone conditions, including jaw osteopenia and periodontal bone loss.

Glaucoma is a major cause of irreversible blindness, characterized by the progressive degeneration of retinal ganglion cells (RGCs), with oxidative stress and apoptosis playing central roles in its pathogenesis. Sirtuin 3 (SIRT3) has demonstrated antioxidant and anti-apoptotic effects in various neurodegenerative diseases; however, its precise role in glaucoma remains unclear. This study aimed to elucidate the neuroprotective function and mechanistic basis of the SIRT3/AMP-activated protein kinase (AMPK) axis in glaucoma.

A rat model of chronic ocular hypertension (COH) was generated using cross-linked hydrogel injection, while an N-methyl-D-aspartate (NMDA)-induced RGC injury model was developed in vitro. SIRT3 overexpression was achieved using adeno-associated virus (AAV) transfection, either alone or combined with the AMPK inhibitor Compound C. Functional and molecular analyses were performed, including intraocular pressure (IOP) measurement, hematoxylin–eosin (H&E) staining, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunofluorescence, Cell Counting Kit-8 (CCK-8) cell viability assay, flow cytometry, Quantitative real-time PCR (qRT-PCR), and western blotting.

In the COH model, both SIRT3 expression and the p-AMPK/AMPK ratio were significantly reduced at weeks 2, 4, and 6 (p < 0.05). Overexpression of SIRT3 lowered IOP, preserved retinal thickness, and decreased the number of TUNEL-positive cells (p < 0.001), while Compound C partially reversed these effects (p < 0.05). In addition, SIRT3 overexpression markedly educed reactive oxygen species (ROS) accumulation (p < 0.001) and restored the p-AMPK/AMPK ratio (p < 0.001), both of which were partially inhibited by Compound C. In NMDA-induced RGCs, SIRT3 overexpression significantly increased SIRT3 mRNA levels (p < 0.01), enhanced cell viability (p < 0.001), and suppressed apoptosis (p < 0.001), with these effects attenuated by Compound C (p < 0.01). The reduction of ROS and activation of AMPK by SIRT3 in this model were also partly reversed by AMPK inhibition (p < 0.01).

This study provides the first comprehensive in vivo and in vitro evidence in glaucoma models that SIRT3 confers neuroprotection in experimental glaucoma, primarily through activation of the AMPK signaling pathway. These findings identify the SIRT3/AMPK axis as a novel mechanistic target and suggest a promising therapeutic strategy for IOP-independent neuroprotection in glaucoma.

Gastric cancer (GC) remains a major global health burden, particularly in East Asia, with complex etiologies involving Helicobacter pylori infection, diet, host genetics, and environmental exposures. GC development follows the Correa sequence (CS), a multistep cascade from gastritis to atrophy, erosion, and carcinoma. Although gut microbiota (GM) dysbiosis and metabolic reprogramming have each been implicated in GC, their integrated dynamics across CS remain incompletely defined.

We recruited participants across five groups: normal controls (G1), gastritis (G2), atrophy (G3), erosion (G4), and GC (G5). Fecal and gastric tissue samples were analyzed using 16S rRNA sequencing and untargeted metabolomics under both ion modes. Microbial diversity was assessed by α- and β-diversity indices, linear discriminant analysis effect size (LEfSe), and functional prediction. Metabolic features were profiled by UHPLC-Q Exactive Orbitrap MS, and differential metabolites were identified using t-tests and partial least squares discriminant analysis (PLS-DA). Diagnostic potential was evaluated using receiver operating characteristic (ROC) curves.

Microbial α-diversity decreased significantly with progression, particularly in G3, while compositional shifts included depletion of Bacteroides and Faecalibacterium alongside enrichment of Actinobacteria, Peptostreptococcaceae, and Lachnoclostridium. LEfSe identified Bifidobacterium and Oscillospiraceae as potential biomarkers of advanced stages. ROC analyses demonstrated strong discriminatory power, with the class Actinobacteria achieving an area under the ROC curve (AUC) of 0.935 in distinguishing controls from GC. Fecal metabolomics revealed reductions in anti-inflammatory short-chain fatty acids (SCFAs) and increases in pro-inflammatory metabolites emerging at G3, while tissue metabolomics showed broader reprogramming in GC involving amino acid, nucleotide, lipid, and energy metabolism. Notably, erosion (G4) exhibited transitional features, whereas atrophy (G3) marked a distinct metabolic “breakpoint”.

By integrating GM and metabolomic data, this study delineates stage-specific microbial and metabolic alterations along the CS. Atrophy represents a pivotal inflection point in the transition from homeostasis to carcinogenesis, while erosion serves as a transitional state. Combined microbiota–metabolite signatures hold promise for non-invasive early detection, disease stratification, and mechanistic insights into metabolic dependencies in GC.

Dysregulation of the transforming growth factor (TGF)-β/Ras homolog family member A (RhoA)/Rho-associated protein kinase (ROCK) pathway can lead to fibrotic changes in ocular diseases. The present study investigated its role in epithelial–mesenchymal transition (EMT) and fibrosis in the ciliary body in lens-induced myopia (LIM) guinea pigs.

A lens-induced myopia model was established in guinea pigs. Refraction, axial length, and ciliary body alterations were assessed via quantitative polymerase chain reaction (qPCR), western blot, PCR array, histological, and biomechanical analyses. Upstream mechanisms were explored using Ingenuity Pathway Analysis. Functional experiments were performed using the ROCK inhibitor Y-27632.

Refraction and axial length were increased in the myopic ciliary body in a time-dependent manner. Protein levels of TGF-β1, RhoA, ROCK1, ROCK2, α-smooth muscle actin (α-SMA), and matrix metalloproteinase (MMP)1 were significantly elevated in the myopic ciliary body, peaking at 6 weeks. In the ultra-early stage of lens myopia, functional changes such as refractive errors and increased biological parameters like axial length occur earlier than changes in EMT transcription factor levels. The differentially expressed genes were involved in cell movement, development, growth, proliferation, and transport in early myopia. Compared with those of normal animals, the Ca²⁺ inflow and Young’s modulus of the ciliary body were greater, the ciliary body elasticity was lower, and the degree of tissue fibrosis was aggravated in animals with deepening myopia. Furthermore, ROCK inhibition can alleviate the pathological levels of EMT and fibrosis in the cilia of myopic guinea pigs.

Collectively, our findings indicate that activation of the TGF-β/RhoA/ROCK pathway induces EMT in the ciliary body, promotes Ca²⁺ inflow, and reduces ciliary body elasticity in myopic animals, resulting in tissue fibrosis and dysfunction. It provides a new perspective on the pathological mechanisms of ciliary body fibrosis in the development of myopia.

Acupuncture has been shown to promote gastrointestinal motility. This study explores whether cutaneous transient receptor potential vanilloid 1 (TRPV1)⁺ fibers at Zusanli (ST36) acupoint can mediate the multimodal effects of acupuncture on colorectal motility, as well as examining their mechanistic role.

C57BL/6 mice were subjected to electroacupuncture (EA), manual acupuncture (MA), 46 °C thermal stimulation, and 1% capsaicin at the ST36 acupoint. Colon motility was quantified via the area under the curve (AUC) and contraction amplitude. Immunofluorescent co-localization of TRPV1 with CGRP, NF200, peripherin, and tyrosine hydroxylase (TH) was conducted in TrpV1^Cre mice to determine neural phenotypic subtypes. Furthermore, TrpV1^ChR2-eYFP and TrpV1^NpHR-eYFP transgenic mice that underwent optogenetic activation or silencing of local TRPV1⁺ fibers at ST36 were evaluated for acupuncture-like stimulation effects on colorectal AUC and amplitude.

All applied stimuli in C57BL/6 mice significantly increased colorectal motility parameters (AUC and amplitude, p < 0.05) compared to baseline. TRPV1⁺ somatosensory neurons in the dorsal root ganglion (DRG) predominantly co-expressed with peripherin (46.76%) and CGRP (27%), which are markers of unmyelinated peptidergic fibers, but rarely with NF200 (6%) or TH (< 1%). Optogenetic activation (30 mW blue light) of TRPV1⁺ fibers in TrpV1^ChR2-eYFP mice mimicked acupuncture-like stimuli, with significantly enhanced colorectal AUC and amplitude (p < 0.05). In contrast, optogenetic silencing of TRPV1⁺ fibers with yellow light abolished acupuncture-like stimulation of colorectal motility in TrpV1^NpHR-eYFP mice (p < 0.05).

Through the use of spatiotemporally precise optogenetic control, our study revealed that TRPV1⁺ sensory fibers at ST36 are the major convergent pathway for multimodal (electrical/mechanical/thermal/chemical) enhancement of colorectal motility by acupuncture.

Monoclonal gammopathy of undetermined significance (MGUS) is a precursor to multiple myeloma (MM), but the mechanisms of progression remain unclear.

Transcriptomic datasets procured from the Gene Expression Omnibus (GEO) underwent thorough analysis to ascertain disease-related modules using weighted gene co-expression network analysis. A prognostic model (MGUSscore) was constructed via least absolute shrinkage and selection operator (LASSO) regression within the GSE136337 cohort and validated across independent datasets (The Cancer Genome Atlas - multiple myeloma [TCGA-MM], GSE4581, GSE57317). Crucially, the investigation integrated original single-cell ATAC-seq profiling, immune landscape characterization, and pharmacogenomic sensitivity prediction. Protein-level disparities were validated in clinical specimens using immunohistochemistry and multiplex immunofluorescence.

DAP3 and UBE2S were identified as central drivers of progression. The MGUSscore effectively stratified patients into risk categories, with high-risk individuals exhibiting significantly inferior survival outcomes (p < 0.001). Notably, the high-risk group was characterized by distinct immune infiltration patterns and predicted responsiveness to specific chemotherapies. Experimental validation confirmed markedly elevated DAP3 and UBE2S protein expression in MM compared to MGUS tissues.

Collectively, DAP3 and UBE2S may constitute promising therapeutic targets for MM intervention, meriting additional investigative efforts.

This study aims to examine the roles and mechanisms of action of bellidifolin (BEL) in alleviating doxorubicin-mediated cardiotoxicity using network pharmacology and experimental validation .

Mice with doxorubicin-induced cardiotoxicity were randomly assigned to control, model, BEL, and dexrazoxane (DEX) groups. Echocardiography, histological staining, network pharmacology, and molecular validation were employed to assess cardiac function and myocardial injury. Immunohistochemical staining, western blotting, and RT-qPCR were used to confirm predicted targets and fibrosis biomarkers.

In vivo experiments demonstrated that BEL significantly improved cardiac function, as indicated by enhanced Ejection Fraction (EF) and Fractional Shortening (FS) compared to the model group (p < 0.01). BEL also notably reduced myocardial injury markers, including creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH) (p < 0.01), and alleviated doxorubicin-induced myocardial fibrosis. Network pharmacology identified 61 common target genes for BEL and cardiotoxicity. Proteinprotein interaction (PPI) network analysis highlighted 16 core genes, including transforming growth factor (TGF)-β1. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses revealed that BEL’s action pathways were primarily linked to the PI3K-AKT signaling pathway. Molecular docking and dynamic simulations showed a strong binding affinity between BEL and the core target TGF-β1. In vivo validation confirmed that BEL significantly downregulated the expression of TGF-β1, α-smooth muscle actin (SMA), collagen I (Col I), and collagen III (Col III) in myocardial tissue (p < 0.01 or p < 0.05), while activating the PI3K-AKT signaling pathway (p < 0.01 or p < 0.05).

BEL presents as a promising therapeutic candidate for cardiotoxicity, likely through its anti-fibrotic effects via the reduction of TGF-β1, α-SMA, Col I, and Col III expression, alongside regulation in the PI3K-AKT signaling pathway.

Triple-negative breast cancer (TNBC) is an aggressive malignancy that lacks effective treatment. Immune infiltration plays an important role in anti-tumor responses. Serpin family G1 (SERPING1), a biomarker associated with immune infiltration, has been implicated in multiple cancers, but its role in TNBC remains unclear.

RNA sequencing and clinical data for TNBC were obtained from the Gene Expression Omnibus, the Cancer Genome Atlas, and the Molecular Taxonomy of Breast Cancer International Consortium databases. First, the expression, prognostic value, and biological functions of SERPING1 were analyzed. Then, the tumor microenvironment (TME) was comprehensively characterized, and the relationship between SERPING1 expression and immunotherapy response was assessed. Immunohistochemical staining was performed to confirm SERPING1 expression and the abundance of CD4+ T cells and CD8+ T cells in clinical specimens. Finally, single-cell analysis was conducted to investigate the role of SERPING1 in immune cell activation.

SERPING1 was downregulated in TNBC and was an independent predictor of survival. Functionally, SERPING1 activated the immune response in TNBC patients. Mechanistically, elevated SERPING1 levels lead to increased immune cell infiltration, particularly of CD4+ and CD8+ T cells, in the TME. Moreover, SERPING1 was primarily localized in cancer-associated fibroblasts (CAFs), with SERPING1+ apCAFs exhibiting increased communications with anti-tumor immune cells at the single-cell level.

SERPING1 contributes to enhanced immune cell infiltration, desirable immunotherapy response, and improved prognosis. It thus can be utilized as a promising biomarker for immune infiltration and prognosis. These findings provide novel insights into TME-related immune regulation and may inform strategies to enhance immunotherapy efficacy in TNBC.

Lung cancer is the leading cause of cancer-related mortality worldwide, and metastasis is the key factor leading to patient death. Epithelial–mesenchymal transition (EMT), which is crucial to tumor metastasis, is primarily regulated by EMT transcription factors, such as Twist1. As an RNA-binding protein, far upstream element binding protein 3 (FUBP3) shows aberrant expression in various tumors; however, its mechanistic role in lung cancer metastasis remains unclear. This study aims to elucidate the functional role of FUBP3 in lung cancer metastasis and its molecular mechanism in the regulation of Twist1.

Bioinformatics analysis was conducted to examine FUBP3 expression patterns in lung cancer and its association with patient prognosis. The Cancer Genome Atlas database was used, and FUBP3 protein expression levels were detected in clinical lung cancer tissues by immunohistochemical analysis. Lung cancer cell lines with FUBP3 knockdown were established, and the effects of FUBP3 on the metastatic capacity of lung cancer were assessed using Transwell migration and invasion assays, 3D spheroid invasion experiments, and tail vein injection metastasis models. Changes in the expression levels of EMT markers were detected by western blot, quantitative real-time polymerase chain reaction, and immunofluorescence. The interaction between FUBP3 and signal transducer and activator of transcription 3 (STAT3) was verified by co-immunoprecipitation (Co-IP), proximity ligation assay, and immunofluorescence co-localization. The effects of STAT3 inhibitor S3I-201 on FUBP3-mediated pro-metastatic functions were assessed.

Bioinformatics analysis revealed high FUBP3 expression in lung cancer tissues, which correlated with poor patient prognosis. Notably, patients with distant metastasis (M1) stage exhibited higher FUBP3 expression than those at the no distant metastasis (M0) stage. Functional experiments confirmed that FUBP3 silencing inhibited the migration and invasion of lung cancer cells, as well as the formation of pulmonary metastatic foci in vivo. The knockdown of FUBP3 led to an increase in the expression of the epithelial marker E-cadherin and downregulated the expression of the mesenchymal marker vimentin, indicating that FUBP3 promotes lung cancer metastasis by promoting EMT. Subsequent analysis indicated that FUBP3 facilitates lung cancer progression by upregulating Twist1 expression. Both exhibit positive correlations in lung cancer patient tissues. Co-IP and immunofluorescence assays demonstrated a direct interaction between FUBP3 and STAT3 proteins. STAT3 silencing counteracted pro-metastatic effects associated with FUBP3 overexpression in lung cancer metastasis. Treatment with S3I-201 effectively reversed the pro-metastatic phenotype in cells with high FUBP3 expression, restored the typical patterns of EMT marker expression, and reduced the formation of metastatic foci in the in vivo metastasis model.

This study reveals the critical role of FUBP3 in lung cancer metastasis and identifies a new regulatory axis involving FUBP3–STAT3–Twist1. FUBP3 interacts with STAT3, enhancing STAT3-dependent Twist1 expression, which promotes EMT and metastasis. FUBP3 functions as a prognostic biomarker, and STAT3 inhibitors present therapeutic strategies for lung cancer, offering novel insights for precision treatment.

Cervical cancer (CC) is one of the most prevalent gynecological malignancies. The expression and functional role of the long non-coding RNA (lncRNA) Ras-related protein Rab-11B antisense RNA 1 (RAB11B-AS1) in CC remain poorly understood.

The expression profile of lncRNA RAB11B-AS1 across multiple cancer types was initially assessed using data from The Cancer Genome Atlas. Its expression in CC tissues and lesions of varying pathological grades was subsequently validated via RNA in situ hybridization. To investigate its functional role in CC, a combination of transcriptomic, proteomic, and functional assays was employed to delineate the molecular role of RAB11B-AS1. The effects of alterations in RAB11B-AS1 expression on cervical cancer growth were ultimately validated in vivo.

LncRNA RAB11B-AS1 was downregulated in CC and associated with a favorable patient prognosis. Functionally, RAB11B-AS1 promoted apoptosis while suppressing proliferation, migration, and invasion of CC cells in vitro, and inhibited tumor growth in vivo. Mechanistically, RAB11B-AS1 upregulated ribosomal protein L26 (RPL26) expression. Notably, RAB11B-AS1 suppressed cervical cancer progression by activating the p53 pathway via RPL26. Critically, in vitro and in vivo experiments confirmed that RPL26 knockdown abrogates the tumor-suppressive functions of RAB11B-AS1, establishing RPL26 as a pivotal downstream effector of RAB11B-AS1 in CC.

Our findings demonstrate that lncRNA RAB11B-AS1 suppresses cervical cancer progression primarily through upregulation of RPL26 and suggest that RAB11B-AS1 may serve as a potential biomarker and therapeutic target in cervical cancer.

Glioblastoma (GBM) is an exceptionally aggressive type of brain tumor with a poor prognosis, underscoring the urgent need to identify new molecular targets for therapeutic development. The objective of this research is to clarify the molecular interactions affected by the oncometabolite D-2-hydroxyglutarate (D-2-HG) within the framework of GBM.

Differential expression analysis of multi-omics data identified potential target genes linked to GBM pathogenesis. To enhance our understanding of the binding interactions between D-2-HG and the identified target proteins, we utilized an integrated methodology encompassing various machine learning algorithms, network pharmacology techniques, and molecular docking.

A sum of 135 genes was recognized as possible targets through which D-2-HG exerts its effects in GBM. The ensuing analysis, utilizing machine learning techniques, identified six crucial genes [eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1), fatty acid binding protein 3 (FABP3), potassium voltage-gated channel subfamily Q member 2 (KCNQ2), epithelial cell adhesion molecule (EPCAM), sphingosine-1-phosphate receptor 5 (S1PR5), and metabotropic glutamate receptor 3 (GRM3)] as key regulators. Among these, FABP3, KCNQ2, EPCAM, S1PR5, and GRM3 were significantly downregulated, whereas EIF4EBP1 was markedly upregulated (p < 0.05). Molecular docking simulations indicated a strong binding affinity of D-2-HG towards the target proteins.

Our study suggests that D-2-HG plays a significant role in the pathogenesis of GBM by modulating specific genes and signaling pathways. Utilizing machine learning techniques, we identified six essential regulatory genes, and further molecular docking simulations revealed a strong affinity of D-2-HG for these critical targets. Collectively, these results establish a substantial basis for future investigations into the mechanistic role of D-2-HG in GBM oncogenesis.

Alveolar echinococcosis (AE) is a serious zoonotic parasitic disease. This study aimed to investigate the mechanisms underlying the formation of the dense fibrotic band surrounding hepatic alveolar echinococcosis (HAE) lesions, which impedes chemotherapeutic drug penetration. Additionally, the roles of Interleukin-33 (IL-33) and eosinophils in the progression of fibrosis within this band were examined.

IL-33/suppression of tumorigenicity 2 (ST-2) expression levels were compared between patients with HAE and healthy controls, as well as between close to lesion tissues (CLT) and distant from the lesion tissues (DLT) using enzyme-linked immunosorbent assay (ELISA), western blot, and immunohistochemistry. Immunofluorescence co-localization analysis was performed to examine IL-33/ST-2 and eosinophil distribution. Masson’s trichrome staining was used to evaluate fibrosis in AE lesions. Cellular assays were carried out to assess the effects of IL-33 on eosinophil phagocytosis and migration, as well as its impact on α-smooth muscle actin (α-SMA) expression in hepatic stellate cells (HSCs).

ELISA findings indicated significantly elevated serum IL-33/ST-2 levels in patients with AE compared with healthy controls (p < 0.05). Immunohistochemistry and western blot analyses demonstrated higher IL-33/ST-2 expression in CLT than in DLT (p < 0.05), with IL-33/ST-2 and eosinophils exhibiting a highly consistent distribution within CLT. Masson’s trichrome staining confirmed increased fibrosis in CLT. Cellular assays showed that IL-33 enhanced eosinophil phagocytosis and migration, while IL-33 stimulation upregulated α-SMA expression on the HSC surface, with this effect being more pronounced in the presence of eosinophils.

IL-33 contributed to microenvironmental fibrosis within AE lesions via eosinophil-mediated mechanisms, highlighting a potential therapeutic target to improve chemotherapy efficacy in patients with AE.

Identifying oncogenic drivers with broad relevance across multiple cancer types is critical for developing novel therapeutic strategies. Kinesin family member 18B (KIF18B) is involved in mitotic regulation, but its comprehensive role and clinical significance across human malignancies remain poorly understood. This study performed a comprehensive pan-cancer analysis of KIF18B and experimentally validated its role in lung adenocarcinoma (LUAD).

We conducted a comprehensive bioinformatic analysis using public databases to evaluate the expression profile, prognostic value, and potential biological functions of KIF18B across various human cancers. Based on these findings, LUAD was selected for further investigation. We evaluated KIF18B protein levels in LUAD cell lines (A549, HCC827, H1975) and compared them to a normal bronchial epithelial cell line (BEAS-2B). Subsequently, KIF18B was silenced in A549 cells using small interfering RNA (siRNA), and its effects on cell proliferation, migration, and invasion were examined using colony formation, wound-healing, and Transwell assays.

Our analysis across various cancers revealed that KIF18B is markedly overexpressed, including in LUAD, and this high expression correlates with poor prognosis in patients across different cancer types. In line with these bioinformatic results, our experiments confirmed that KIF18B protein levels were elevated in LUAD cell lines compared with normal controls. Functional assays demonstrated that knockdown of KIF18B in A549 cells significantly suppressed colony-forming ability and impaired migratory and invasive capacities.

This study, integrating pan-cancer bioinformatic analysis with experimental validation, establishes KIF18B as a widely expressed oncogene with significant prognostic value. Our findings in LUAD confirm its crucial role in promoting key malignant phenotypes. Thus, KIF18B emerges as a valuable prognostic biomarker and a potential therapeutic target, not only for LUAD but potentially for a wider array of cancers.

Turmeric-derived exosome-like nanoparticles (TELNs) are nanoscale vesicles of plant origin with therapeutic potential. However, the specific efficacy and mechanisms of TELNs in inhibiting non-small cell lung cancer (NSCLC) remain unclear. This study investigated the effects of TELNs on NSCLC by epigenetically regulatiing histone acetyltransferase human males absent on the first (hMOF) and histone H4K16 acetylation (H4K16ac).

TELNs were isolated from turmeric using differential centrifugation and characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and zeta potential measurements. Cellular uptake was assessed via PKH26 labeling. In vitro assays evaluated the effects of TELNs on apoptosis (annexin V/PI staining, JC-1 mitochondrial depolarization, caspase-3 cleavage) and proliferation (CCK-8). The in vivo efficacy of TELNs was examined in A549 xenografts. Bioinformatics and molecular docking analyses revealed the interaction of curcumin in TELNs with hMOF, while RNA interference validated the role of hMOF in TELN-mediated apoptosis and migration suppression.

TELNs exhibited exosome-shaped morphology and efficient uptake by A549 cells. Treatment with TELNs induced apoptosis and reduced tumor volume by 58.1%. Mechanistically, TELNs upregulated hMOF expression and H4K16ac levels. RNA interference confirmed that knockdown of hMOF weakened the effect of the TELNs. Molecular docking suggested curcumin in TELNs may interact with hMOF.

This study reveals a novel epigenetic mechanism wherein TELNs suppress NSCLC by activating hMOF/H4K16ac. Curcumin within TELNs increases hMOF levels, thus positioning TELNs as a potential nanotherapeutics with the capacity for epigenetic modulation. Our findings underscore the potential of TELNs in NSCLC treatment and highlight hMOF as a therapeutic target.

N6-methyladenosine (m6A) RNA methylation is a crucial epigenetic modification that plays an essential role in regulating diverse biological processes. Accurate identification of m6A sites is therefore fundamental to understanding its regulatory mechanisms. In this study, we proposed DT-m6A, a novel deep learning framework that integrates DenseNet and Transformer architectures for accurate m6A site identification across diverse cell lines and tissues.

RNA sequences are first encoded using nucleotide chemical properties (NCP) for initial features extraction, after which DenseNet captures and reuses local sequence features through dense connections. The Transformer module then models long-range dependencies and extracts nonlinear representations, in which Batch Normalization replaces the conventional Layer Normalization in both sublayers to enhance training stability. Finally, a fully connected layer predicts m6A modification sites.

Evaluated on 11 independent test sets spanning eight cell lines and three tissue types, DT-m6A demonstrated robust performance, achieving average accuracy (ACC) of 76.97%, Matthews correlation coefficient (MCC) of 54.27%, precision (PRE) of 75.18%, recall (REC) of 79.76%, and F1 score of 77.26%.

DT-m6A surpassed the state-of-the-art method MST-m6A by 0.63% in average accuracy (p = 0.0023) and 1.4% in mean MCC (p = 0.0012) across 11 independent test sets. Although its performance on the CD8T and MOLM13 cell lines was comparable to MST-m6A, DT-m6A consistently achieved superior results across all other cell lines and tissues. Overall, DT-m6A effectively captures both local patterns and global dependencies in RNA sequences, improving prediction performance across diverse biological contexts.

Epithelial-mesenchymal transition (EMT) is a fundamental biological process. During EMT, epithelial cells transition to a mesenchymal phenotype, thereby contributing to embryonic development, tissue renewal, and cancer progression. EMT is a well-recognized key driver of tumor invasion and metastasis. However, the transcriptional differences between the physiological and cancer-associated EMT remain incompletely understood.

In the present study, we applied an integrative framework that combined transcriptomic profiling, functional enrichment analysis, and machine learning. The analysis was performed on 89 RNA-sequencing datasets derived from mouse cell lines and tissues, encompassing both normal and malignant contexts. This approach aimed to identify and prioritize genes systematically and signaling pathways associated with EMT.

Differential gene expression and pathway enrichment analyses revealed an over-representation of shared core biological processes related to cell adhesion, cytoskeletal remodeling, and morphogenesis, in both normal and cancer-associated EMT. Nonetheless, cancer-associated EMT exhibited additional enrichment for developmental and neural-related programs, including neurogenesis and gliogenesis. Machine learning models consistently prioritized candidate EMT biomarkers, with greater transcriptional heterogeneity observed in cancer samples.

Collectively, this integrative analysis delineates distinct transcriptional profiles between malignant and physiological EMT. The enrichment of neural-related programs in cancer-associated EMT highlights potential mechanisms that contribute to malignant cellular plasticity. In addition, the analysis identifies candidate biomarkers for future investigation of EMT heterogeneity.

Araliadiol, a triterpenoid compound isolated from Centella asiatica, exhibits diverse biological activities, including anti-cancer, neuroprotective, and hair growth-promoting properties. However, its protective effects against skin damage caused by environmental pollutants, such as urban particulate matter (UPM), remain unexplored. Given the critical role of oxidative stress in UPM-induced cellular damage, we investigated the potential of araliadiol as a dermoprotective agent and explored its underlying molecular mechanisms.

The stability of araliadiol was evaluated at various temperature conditions and solvent conditions using high-performance liquid chromatography (HPLC). To explore the biological functions and signaling pathways affected by araliadiol, bioinformatic analyses including Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Monarch phenotype analysis were performed. Cellular responses to araliadiol were assessed in HaCaT and HEK293T cells by measuring reactive oxygen species (ROS) levels and transcription of antioxidant genes. Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and activator protein-1 (AP-1) signaling pathway was further examined using quantitative polymerase chain reaction (PCR), luciferase assay, western blotting, and immunofluorescence staining. The interaction between araliadiol and mitogen-activated protein kinase kinase 7 (MKK7) was investigated through molecular docking and cellular thermal shift assay (CETSA). DNA damage and apoptosis were examined using the comet assay, γ-H2AX staining, Annexin V/PI flow cytometry, and protein expression analysis.

Araliadiol significantly reduced intracellular levels of ROS by upregulating key antioxidant genes, including HO-1, NQO1, TXNRD1, GCLC, and GCLM. Mechanistically, araliadiol promoted the expression and nuclear translocation of Nrf2, a master transcription factor involved in antioxidant defense. In parallel, araliadiol selectively activates the c-Jun N-terminal kinase (JNK)–AP-1 signaling cascade by directly binding to and activating MKK7, an upstream kinase involved in oxidative stress responses. Given the close association between oxidative stress, DNA damage, and apoptosis, we further investigated the protective capacity of araliadiol in this context. Araliadiol markedly attenuated UPM-induced DNA damage and apoptosis, as evidenced by reduced comet tail formation, decreased γ-H2AX levels, a lower proportion of Annexin V-positive cells, and modulation of apoptosis-related proteins. Meanwhile, although UPM exposure induced the expression of specific antioxidant-associated genes (TXNRD and GCLC), HO-1 protein expression, and AP-1 signaling, it failed to activate Nrf2 transcriptional activity. Instead, UPM exposure resulted in elevated intracellular ROS accumulation and increased DNA damage.

Our findings suggest that UPM exposure alone elicited limited stress-adaptive antioxidant responses without effective cytoprotection. In contrast, araliadiol treatment independently activated robust antioxidant and cytoprotective signaling. Moreover, under UPM exposure, araliadiol further enhanced cellular defense through the activation of the Nrf2 and JNK–AP-1 signaling pathways. These results highlight the therapeutic potential of araliadiol as a dermoprotective agent derived from Centella asiatica, particularly in mitigating pollutant-induced skin damage.