Biomedical subjects

Meng Xu

Publications and source records attributed to Meng Xu.

3 recordsLinked to original sources

PubMed2026

Icaritin Sensitizes Hepatocellular Carcinoma to PD-L1 Therapy by NQO1-Dependent Ferroptosis Induction.

Hepatocellular carcinoma (HCC) remains challenging with limited immunotherapy response. Despite its clinical promise in advanced HCC, the mechanisms of icaritin, especially concerning ferroptosis induction and immune modulation, remain elusive. This study aims to determine if the antitumor effect of icaritin involves the induction of ferroptosis via NAD(P)H quinone oxidoreductase 1 (NQO1) and if it can augment the efficacy of programmed cell death 1 ligand 1 (PD-L1) therapy by potentiating natural killer (NK) cell activity. Using human HCC cell lines (Huh7, Hep3B, PLC/PRF/5, SNU-449, and MHCC97-H) and two synergistic mouse models (Hepa1-6 and SgPten/c-Met), we examined icaritin's inhibition of tumor growth and induction of ferroptosis via the NQO1 pathway, monitoring key markers (reactive oxygen species [ROS], glutathione peroxidase 4 [GPX4], ferritin heavy chain 1 [FTH1]). The NQO1 inhibitor dicoumarol was employed to validate the pathway. Tumor microenvironment (TME) remodeling was assessed through cancer-associated fibroblasts (CAFs) markers and immune cell profiling, focusing on NK cell infiltration. Combination therapy with anti-PD-L1 was tested in vivo. Icaritin significantly inhibited HCC growth in vitro and in vivo. Its antitumor effect was mediated by NQO1-mediated ferroptosis, via elevated ROS, diminished mitochondrial membrane potential, and downregulated GPX4 and FTH1. Analysis of The Cancer Genome Atlas (TCGA) data revealed that NQO1 is overexpressed in human HCC tissues. Icaritin enhanced NK cell infiltration while reducing CAF abundance and suppressing recombinant focal adhesion kinase (FAK) and discoidin domain receptor 1 (DDR1) signaling. Notably, icaritin synergized with anti-PD-L1 therapy to enhance tumor suppression without increasing toxicity, correlating with potentiated NK cell immunity. Our findings demonstrate that icaritin triggered NQO1-mediated ferroptosis and remodeled TME to enhance NK cell recruitment and PD-L1 therapy efficacy. This provides rationale for evaluating icaritin-based combination immunotherapy in HCC through dual action on ferroptosis and NK cell activation.

Ferroptosis↗

PubMed2025

Bioavailable testosterone reduces the risk of lung squamous cell carcinoma: a comprehensive data study.

BACKGROUND: The association between testosterone and lung cancer remains unclear. This study investigates the relationship between testosterone levels and lung cancer risk, focusing on bioavailable testosterone levels (BTLs), total testosterone levels (TTLs), and sex hormone-binding globulin (SHBG) in relation to lung cancer subtypes. METHODS: We utilized bidirectional and multivariable Mendelian randomization (MR) analyses based on genome-wide association studies (GWAS) to assess causal links. To validate the findings clinically, immunohistochemical (IHC) staining for androgen receptor (AR) expression and survival analyses were conducted on a cohort of 90 patients with lung squamous cell carcinoma (LUSC). RESULTS: MR analysis demonstrated that higher BTLs were significantly associated with a reduced risk of LUSC (OR = 0.365, P = 0.001), while no significant associations were observed for TTLs or SHBG. Reverse MR analysis found no causal effect of lung cancer on testosterone levels. Multivariable MR confirmed BTLs as an independent protective factor. In the clinical cohort, AR expression was significantly associated with better prognosis, showing improved median progression-free survival (12.3 vs. 9.0 months, P = 0.01) and median overall survival (35.3 vs. 29.4 months, P < 0.01). Cox regression identified AR expression as an independent protective factor for patient outcomes. However, study limitations include potential residual confounding, ethnic heterogeneity between European GWAS data and Asian clinical cohorts, and the lack of direct experimental validation. CONCLUSIONS: Our findings suggest that higher BTLs may play a protective role against LUSC. BTLs and AR expression show potential as valuable biomarkers for the diagnosis and prognostic assessment of LUSC.

Humans↗

PubMed2025

Haplotype-resolved telomere-to-telomere genome assembly of Populus lasiocarpa unveils retrotransposon-driven centromere evolution.

Centromeres, essential for chromosome segregation, exhibit remarkable evolutionary dynamism in sequence composition and structural organization. Here, we report the first haplotype-resolved, telomere-to-telomere genome assembly of Populus lasiocarpa (PLAS) and precisely map all 38 functional centromeres through CENH3 ChIP-Seq. Unlike classical satellite-rich centromeres in model plants, PLAS centromeres lack abundant satellite arrays but are dominated by retrotransposons, particularly RLG and RIL elements, which form intricate nested TE arrays within the functional centromeric regions, disrupting their structural integrity and driving their evolution. Comparative analysis with P. trichocarpa reveals a conserved retrotransposon-dominated architecture, despite minimal sequence conservation. We propose a cyclic model of centromere evolution in which autonomous retrotransposons destabilize functional centromeres through epigenetic erosion, triggering neocentromere formation at pericentromeric sites enriched in transposable elements (TEs) and tandem repeats (TRs). These neocentromeres either succumb to recurrent retrotransposon invasions or stabilize through KARMA-mediated TR expansion, ultimately giving rise to satellite-rich centromeres. Our work redefines centromeres as dynamic, epigenetically plastic domains shaped by retrotransposon-TR antagonism, challenging the satellite-centric paradigm and offering novel insights into plant genome evolution.

Retroelements↗