Biomedical subjects

Huan Wang

Publications and source records attributed to Huan Wang.

6 recordsLinked to original sources

PubMed2026

Decoding Primary Open-Angle Glaucoma: A Multi-Omics Approach to Identify Druggable Effector Genes.

PURPOSE: Genomewide association studies (GWAS) have identified numerous primary open angle glaucoma (POAG) risk loci, yet most reside in non-coding regions with unclear function. Mapping these loci to effector genes can elucidate disease mechanisms, identify functionally conserved variants, improve cross-ancestry risk prediction by reducing population-specific noise, and uncover shared therapeutic targets. METHODS: Here, we integrate European POAG GWAS with six types of multi-omics molecular Quantitative Trait Locis (xQTLs) using multi-trait colocalization to identify candidate effector variants and evaluate their cross-population relevance using genetic risk score (GRS) analysis, and their therapeutic potential through drug target prioritization. RESULTS: We identified 25 POAG effector variants colocalized with at least one xQTLs. In non-European populations, effector variants showed stronger effect size correlations with Europeans than non-colocalized variants (Pearson r2 = African 0.85 vs. 0.71; East Asian 0.81 vs. 0.69; and Latin American 0.91 vs. 0.75). Effector variants also had smaller allele frequency variations across populations (average interquartile range [IQR] = 0.15 vs. 0.20). The genetic risk score based on effector variants performed comparably to the genome-wide significant single-nucleotide polymorphism (SNP)-based GRS in non-European populations. Drug prioritization identified zinc, copper, sunitinib, probucol, and astemizole as potential common therapeutic agents for POAG and its subtypes. CONCLUSIONS: Our findings offer deeper insight into the molecular mechanisms underlying glaucoma and effector variants for developing more robust GRS models and broadly effective therapeutic strategies for POAG.

Humans↗

PubMed2026

Exploring the therapeutic targets and signaling mechanisms of quercetin activity against radiation skin ulcer based on the observational research of network pharmacology.

Radiation skin ulcer is a common adverse complication after radiotherapy. Currently, there is no efficient therapy for this complication. In this study, we searched for the potential pathological targets of radiation skin ulcer and the potential pharmacological targets of quercetin, respectively, and obtained the potential therapeutic targets after intersection. Subsequently, an array of bioinformatics assessments on possible therapeutic targets was conducted, encompassing functional enrichment studies, analysis of protein interaction networks, identification of key targets, and validation through molecular docking. The enrichment analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways shows that the therapeutic effect of quercetin on radiation skin ulcer may be through targeting aging cells. In addition, we identified 5 core targets, including AKT1, EGFR, MAPK3, SRC, and TP53. They are significantly enriched in EGFR tyrosine kinase inhibitors (SRC, AKT1, EGFR, and MAPK3) and epidermal growth factor receptor signaling pathways (SRC, EGFR, and AKT1), indicating the importance of EGFR signaling. Quercetin may have a therapeutic effect on radiation skin ulcer by targeting aging cells. Specifically, it may act through 4 core targets, including AKT1, EGFR, SRC, and TP53.

Quercetin↗

PubMed2025

The correlation of DPM1 overexpression with immune infiltration and poor prognosis in hepatocellular carcinoma.

BACKGROUND: The DPM1 gene, crucial for glycosylation processes, has shown abnormal expression in various cancers, raising interest in its potential oncogenic role and as a biomarker in hepatocellular carcinoma (HCC). METHODS: Transcriptomic data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. DPM1 expression levels were compared between HCC tissues and adjacent normal tissues. Clinical correlations were assessed using statistical analyses, including survival analysis and multivariate Cox regression. Immune microenvironment profiling was conducted to evaluate associations between DPM1 expression and immune cell infiltration patterns. RESULTS: Elevated DPM1 levels were associated with advanced tumor stages (P < 0.001), higher pathologic T stage (P < 0.001), increased histologic grade (P < 0.001), tumor positivity (P < 0.001), tissue inflammation (P < 0.001), and elevated alpha-fetoprotein levels (AFP > 400 ng/mL, P < 0.05). Multivariate Cox regression analysis identified DPM1 as an independent prognostic factor for reduced overall survival (HR = 1.990, 95% CI 1.390-2.848). Immunological analysis revealed that DPM1 expression was positively correlated with T helper cells (R = 0.268, P < 0.001) and Th2 cells (R = 0.295, P < 0.001), and negatively correlated with plasmacytoid dendritic cells (R=-0.291, P < 0.001) and cytotoxic cells (R=-0.284, P < 0.001). CONCLUSIONS: DPM1 serves as a promising prognostic biomarker in HCC, with its expression correlating with unfavorable clinical outcomes and immune landscape alterations. Future studies should further validate DPM1's impact on ferroptosis and immune evasion in HCC, and explore its potential as a therapeutic target.

DPM1↗

PubMed2025

A pancreatic cancer organoid biobank links multi-omics signatures to therapeutic response and clinical evaluation of statin combination therapy.

Chemotherapy remains the primary treatment for pancreatic ductal adenocarcinoma (PDAC), but most patients ultimately develop resistance. Here, we established 260 pancreatic cancer organoid lines, followed by extensive multi-omics profiling and therapeutic sensitivity assessments. Integrated analyses uncovered 6 novel coding and 35 noncoding driver candidates. We discovered 2,794 multi-omics features associated with drug sensitivity and 322 features linked to radiation sensitivity. Pharmacogenomic analyses revealed that chemoresistant organoids exhibited enrichment in protein glycosylation and cholesterol metabolism pathways. Notably, statins effectively targeted chemoresistant PDAC organoids. Statin treatment attenuated protein glycosylation, cholesterol levels, and the epithelial-to-mesenchymal transition (EMT) signature in PDAC organoids. We conducted a single-center, single-arm, phase 2 clinical trial (NCT06241352) combining atorvastatin with chemotherapy in patients with advanced pancreatic cancer. Among 37 patients, 26 (70.3%) demonstrated a response, with tumor markers decreasing by more than 20%, suggesting durable responses and potential clinical benefits in this challenging patient population.

Humans↗

PubMed2025

Construction and In Vitro and In Vivo Analysis of Coxsackievirus B4 Reporter Viruses: Attenuated Virulence but Highly Efficient for Antiviral Drug Screening and Evaluation.

Coxsackievirus B4 (CVB4) is an enterovirus with one of the highest mortality rates following infection, yet research on it remains limited. To enhance the efficiency of CVB4 research, we developed the rCVB4-EGFP and rCVB4-NanoLuc reporter viruses. The replication kinetics of these reporter viruses in SH-SY5Y and HeLa cells were essentially consistent with those of the wild-type CVB4. A strong correlation was observed between the fluorescence and bioluminescence signals of rCVB4-EGFP and rCVB4-NanoLuc and viral titers at specific times postinfection. When evaluating the anti-CVB4 drug fluoxetine using these reporter viruses, the half-maximal effective concentrations derived from fluorescence signals, bioluminescence signal intensities, and viral genome copies were consistent. In In Vivo drug evaluations, because CVB4 can infect various tissues and organs, the bioluminescence signal of rCVB4-NanoLuc effectively demonstrated the antiviral effects of drugs, offering significant advantages over traditional tissue viral titer analysis. The reporter viruses exhibited reduced virulence compared with wild-type CVB4 both In Vitro, in SH-SY5Y and HeLa cells, and In Vivo, in ICR suckling mice. Although this reduced virulence may limit their application for studying pathogenic mechanisms, these reporter viruses can serve as highly efficient tools for high-throughput screening and evaluation of anti-CVB4 drugs, vaccines, and neutralizing antibodies.

Humans↗

PubMed2024

The Protective Role of DDIT4 in Helicobacter pylori-induced Gastric Metaplasia Through Metabolic Regulation of Ferroptosis.

BACKGROUND & AIMS: Helicobacter pylori (H pylori) infection is a significant factor leading to gastric atrophy, metaplasia and cancer development. Here, we investigated the role of the stress response gene DDIT4 in the pathogenesis of H pylori infection. METHODS: Cell lines, transgenic mice, and human tissue samples were implemented. Proteomics were performed on Ddit4+/+ and Ddit4-/- mice infected with H pylori strain PMSS1. C57BL/6 mice were administered with tamoxifen to induce gastric metaplasia. Stomach tissues were analyzed for histopathologic features, reactive oxygen species, Fe2+, lipid peroxidation, expression of DDIT4, and ferroptosis-related proteins. RESULTS: DDIT4 expression was upregulated at 6 hours but significantly decreased at 24 hours in response to H pylori infection in gastric epithelial cells. Gastric DDIT4 were downregulated in INS-GAS mice at 4 months post H pylori infection. Notably, H pylori infection led to more severe gastric metaplasia lesion in Ddit4-knockout mice. The proteomic profiling revealed an increase in ferroptosis in the gastric tissues of infected Ddit4-deficient mice, compared with infected wild-type mice. Mechanistically, knockout of DDIT4 promoted H pylori-induced ferroptosis through the accumulation of lipid peroxides and ROS levels, and alterations in proteins such as GPX4, ALOX15, and HMOX1. Overexpression of DDIT4 counteracted H pylori-induced stem cell marker CD44V9 through modulation of ferroptosis. Similarly, in another mouse model of gastric metaplasia treated with tamoxifen, as well as in human GIM tissues, we observed the loss of DDIT4 and induction of ferroptosis. CONCLUSIONS: Our results indicate that DDIT4 serves as a protective factor against H pylori-induced gastric metaplasia by metabolic resistance to ferroptosis.

Ferroptosis↗