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Biomedical subjects

Yang Gao

Publications and source records attributed to Yang Gao.

4 recordsLinked to original sources

Identification and characterization of anti-chikungunya virus compounds using a biosafe toolkit.

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus for which no specific antiviral therapy is currently available. During the large outbreak in Foshan, Guangdong Province, China, in July 2025, CHIKV rapidly spread to neighboring regions and caused more than 16,000 confirmed cases. In this study, the predominant outbreak strain of CHIKV was selected as the reference sequence to establish a panel of complementary biosafe tools for antiviral compound screening and mechanistic investigation. A virus replicon particle (VRP) system for CHIKV was first constructed and applied to compound library screening, resulting in the identification of three candidate antiviral compounds: MDL-12330A, bazedoxifene acetate, and anidulafungin. To further validate their antiviral activities and investigate their potential mechanisms, CHIKV functional evaluation systems were subsequently established, including vesicular stomatitis virus (VSV)- and murine leukemia virus (MLV)-based pseudovirus systems for viral entry, a replicon RNA system for post-entry replication-associated processes, a replication-defective nsP4 mutant replicon RNA system for primary translation, and a virus-like particle (VLP) system for viral particle assembly and budding assessment. Using these complementary systems, we systematically evaluated the antiviral profiles of the three candidate compounds across multiple stages of the CHIKV life cycle. This analysis revealed distinct stage-specific inhibitory patterns and provided insights into their potential antiviral mechanisms, which warrant validation using authentic CHIKV infection to assess their translational potential.

Chikungunya virus

Expression of PIEZO1 in lung adenocarcinoma correlates with PD-L1 expression, cell migration, and poor prognosis: an exploratory study.

BACKGROUND AND AIMS: Lung adenocarcinoma (LUAD) treatment is challenging process. and the function of PIEZO1, a mechanically sensitive ion channel has not been systematically determined. In this study we aimed to explore the expression, potential associations, and clinical significance of PIEZO1 in LUAD. METHODS AND AIMS: A comprehensive bioinformatics analysis was performed using data from the Cancer Genome Atlas (TCGA) database, the Gene Expression Omnibus (GEO) database and other databases. Experimental validation was performed to confirm the expression patterns and preliminarily examine the associations of PIEZO1 in LUAD cell lines. RESULTS: PIEZO1 expression was significantly lower in LUAD tissues than in normal lung tissues (P&#x2009;<&#x2009;0.05). Its expression was correlated with advanced pathological stage, lymph node involvement, and distant metastasis. High PIEZO1 expression was associated with a distinct immune-related tumor microenvironment, characterized by correlations with the expression levels of multiple immune checkpoint molecules, and was identified as an independent factor associated with poor overall survival (HR&#x2009;=&#x2009;1.49; 95% CI 1.11-2; P&#x2009;<&#x2009;0.007). In vitro experiments confirmed the downregulated PIEZO1 expression in LUAD cell lines, and functional knockdown experiments revealed its association with cell migration and PD-L1 expression. CONCLUSION: This exploratory study revealed that PIEZO1 expression in LUAD cell lines correlated with the expression of immune-related features and EMT-related genes, as well as poor prognosis. In vitro, PIEZO1 knockdown is associated with reduced cell migration and decreased PD-L1 expression. These findings provide a basis for future investigations into the potential role of PIEZO1 in LUAD.

Gene expression

Region-Resolved Integrative Multi-Omic Characterization Reveals Diverse Tumor and Microenvironment Features of Pituitary Neuroendocrine Tumors.

Pituitary neuroendocrine tumors are frequently invasive, with cavernous sinus invasion leading to poor treatment outcomes and high recurrence. Regional differences within these tumors remain poorly understood, hindering targeted therapy development. Here, we present the first integrative multi-omics analysis combining proteomics, metabolomics and single-cell transcriptomics to characterize tumors from the cavernous sinus and saddle regions. Our results reveal profound regional and cellular heterogeneity: cavernous sinus tumors exhibit significantly enhanced cell proliferation, driven by cancer-associated fibroblasts through the IGF1-IGF1R-MAPK1 axis. Cancer-associated fibroblasts in the cavernous sinus secrete IGF1 under regulation of the transcription factor FOXO1, which binds to receptors on tumor cells to activate proliferation. Metabolomic profiling identifies proline as a key enriched metabolite that stimulates cancer-associated fibroblasts to produce collagen fibers, reinforcing a pro-tumorigenic microenvironment. Single-cell transcriptomics further delineates a distinct subpopulation of receptor-positive malignant cells and a high abundance of cancer-associated fibroblasts in the cavernous sinus. These findings establish core mechanisms underlying the aggressive behavior of cavernous sinus-invading tumors, providing novel actionable targets for precision therapeutic strategies tailored to distinct tumor regions.

Humans

Heme oxygenase 1 (HO-1) is a drug target for reversing cisplatin resistance in non-small cell lung cancer.

INTRODUCTION: Platinum-based drugs, the most widely used chemotherapeutic drugs in clinical oncology, have long faced the problem of drug resistance, which is urgently in need of resolution. Identifying biomarkers of drug resistance may help reduce platinum resistance and improve therapeutic efficacy. OBJECTIVES: This study aims to identify potential biomarkers associated with the development of cisplatin resistance in non-small cell lung cancer (NSCLC) and explore mechanisms to overcome chemoresistance. METHODS: NSCLC cisplatin resistance cell lines were constructed, and transcriptome sequencing was performed. Results were validated using Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Molecular docking, proteomics sequencing, and in vitro and in vivo experiments were conducted to evaluate the role of Heme Oxygenase 1 (HO-1) in cisplatin resistance. RESULTS: NSCLC cisplatin resistance cell lines, GEO and TCGA data identified HMOX1, downstream of Nrf2, as a key drug resistance gene induced by cisplatin. Activation of the Nrf2/HO-1 pathway was found to induce ferroptosis resistance, a critical mechanism of cisplatin resistance. Candidate compounds SB 202190 and Nordihydroguaiaretic acid (NDGA) effectively reactivated ferroptosis by inhibiting HO-1, thereby increasing cisplatin sensitivity. CONCLUSION: The Nrf2/HO-1 pathway is a significant contributor to cisplatin resistance in NSCLC. Targeting HO-1 with SB 202190 and NDGA presents a promising strategy to overcome resistance and improve chemotherapy outcomes.

Cisplatin