Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Helicobacter pylori (Hp) is a unipolar, microaerobic, multiflagellar, spiral-shaped Gram-negative bacterium that survives and colonizes human gastric mucosa. As a classⅠcarcinogen associated with gastric cancer, long-term stimulation of gastric mucosa by Hp can cause atrophic gastritis, peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. It has been reported that Hp can cause epithelial-mesenchymal transition (EMT) in gastric epithelial cells, thereby inducing gastric cancer. We review the mechanism of Hp-induced EMT in gastric epithelial cells, in order to provide new insights for early diagnosis and targeted therapy of gastric cancer.

The main mineral component of natural tooth was determined as calcium apatite many years ago; most of them exist in the form of hydroxyapatite with different crystallites. If a tooth decayed, the crystalline of hydroxyapatite would be changed and decomposed. In our experiment, a natural tooth with caries was measured by high resolution XRD equipment: X'pert Pro. Three spots which included normal enamel, normal dentin and caries tissue were analyzed. The results showed that tooth was a kind of biological mixed crystal composed of many crystal phases, the main crystal phase was hydroxyapatite. From normal enamel to normal dentin and to caries tissue, the length of the a-axis of hydroxyapatite crystallite increased, the length of the c-axis of hydroxyapatite crystallite remained unchanged. The crystal sizes were: normal enamel D002 = 27.600 nm; normal dentin D002 = 16.561 nm; caries tissue D002 = 13.163 nm. Crystallinity: normal enamel>normal dentin>caries tissue. According to our experiment, tooth could be conveniently studied by high resolution microdiffracion XRD equipment.
Dental Caries ; metabolism ; Dental Enamel ; chemistry ; Dentin ; chemistry ; Humans ; Tooth ; chemistry ; X-Ray Diffraction ; methods