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by Quan He, Xiong Zou, Chunyan Zheng, Jiawei Zhang, Jialing Li, Liping Hu, Ting Zeng, Zijuan Huang, Peipei Zeng, Jinli Wei, Haichen Cui, Yongjian Su, Hai Li
BackgroundResidual mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains a significant clinical challenge despite standard immunoprophylaxis. Identifying molecular markers is crucial for improved prevention and diagnosis.
MethodsWe conducted a case-control study using the Guangxi Liuzhou HBV MTCT registry. Peripheral blood RNA sequencing (Illumina HiSeq) was performed on infants from HBsAg-positive mothers: cases (HBsAg-positive, n = 6) and controls (HBsAg-negative, n = 10). All infants receive HBIG and the first dose of hepatitis B vaccine within 24 hours after birth, followed by completion of the three-dose vaccination series. Differentially expressed miRNAs (DEMs; adj-p 1) were identified. Target genes were predicted (miRanda/RNAhybrid) and functionally analyzed (GO/KEGG enrichment, PPI network). HBV-associated target genes were identified by cross-referencing GeneCards/NCBI.
ResultsRNA-seq identified 62 DEMs (19 upregulated, 43 downregulated). Target prediction yielded 5,014 genes. Functional enrichment highlighted key pathways and processes. PPI analysis pinpointed highly connected genes. Integration with HBV databases revealed 3 key target genes potentially modulated by 4 specific DEMs (hsa-miR-6747-3p, hsa-miR-4772-3p upregulated; hsa-miR-4676-5p, hsa-miR-485-5p downregulated).
ConclusionThis study identifies dysregulation of 4 key miRNAs and their association with 3 HBV-linked target genes as potential contributors to residual HBV MTCT. These findings provide novel insights into the molecular mechanisms underlying HBV MTCT and suggest potential targets for intervention.
by Zijing Wang, Liyuan Ma, Zhanyuan Sun, Hengyi Lv, Ruxue Ma, Mengqi Ding, Hai Li, Tao Jiang
BackgroundDiethyl phthalate (DEP), a widely used plasticizer with endocrine-disrupting properties, has raised concerns regarding its potential carcinogenic effects. However, its precise role in colorectal cancer (CRC) development remains poorly understood.
MethodsThe chemical structure of DEP was obtained from the PubChem database. Potential targets of DEP were identified through ChEMBL and STITCH databases and intersected with known CRC-related genes to screen for candidate biomarkers. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and signaling pathways involved. Molecular docking was conducted to predict the binding affinities between DEP and core targets. Finally, 200-ns molecular dynamics (MD) simulations using GROMACS were employed to evaluate the binding stability and dynamic behavior of the DEP–target complexes.
ResultsA total of 62 overlapping genes were identified between DEP targets and CRC-associated genes. GO and KEGG enrichment analyses indicated enrichment in epigenetic regulation, chromatin remodeling, and cancer-related signaling pathways, including Notch, TGF-β, and FoxO. Protein–protein interaction analysis identified EP300, EZH2, HDAC1, HDAC2, and KDM1A as key epigenetic regulators. Molecular docking predicted moderate binding affinities between DEP and these targets (−6.6 to −5.7 kcal·mol ⁻ ¹). Subsequent 200-ns MD simulations suggested that DEP formed stable complexes with HDAC1, KDM1A, and EZH2, moderate stability with EP300, and partial dissociation with HDAC2, consistent with hydrophobic and hydrogen-bonding interactions at the binding interfaces.
ConclusionThis study provides a theoretical framework for exploring the molecular mechanisms through which DEP may contribute to CRC development, emphasizing the value of network toxicology in cancer research. These findings may inform future investigations into the risks of DEP exposure and support public health policy and the development of targeted therapeutic strategies.
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