Type 2 diabetes (T2D) is associated with alterations in the oral microenvironment, including microbial dysbiosis and host transcriptional changes. Whether antidiabetic therapies such as semaglutide modulate these alterations in a coordinated manner remains unclear. To investigate the association between semaglutide treatment and coordinated changes in oral microbiota and host transcriptional programs. 16S rRNA sequencing and bulk RNA-seq were performed on oral samples from WT, db/db, and semaglutide-treated db/db mice. Microbial diversity, taxonomic composition, gene expression, and integrative analyses were conducted. β diversity revealed clear separation between WT and db/db groups, with treated samples partially shifting toward the WT state, while α diversity showed no significant difference. The dysbiosis index was increased in db/db mice and reduced following treatment. At the genus level, Bacillus and Delftia decreased, whereas Streptococcus increased in db/db mice, with opposite trends after treatment. Transcriptomic analysis identified interferon-enriched and metabolic-associated gene clusters, with modulation of interferon- and antiviral-response pathways following treatment. Integration analyses demonstrated reorganization of gene-microbiota networks and significant correlations between cluster-specific transcriptional programs and dysbiosis. T2D is associated with coordinated alterations in oral microbiota and host transcription, and semaglutide treatment is accompanied by partial remodeling of these features.

The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists. The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers, based on factors such as detailed clinical medical history inquiry, histopathological examination, and ulceration-related systemic diseases screening. Not only it can provide a standardized procedure of oral ulceration, but also it can improve the diagnostic efficiency, in order to avoid misdiagnosis and missed diagnosis.

Exposure to radiation causes DNA damage; hence, continuous surveillance and timely DNA repair are important for genome stability. Epigenetic modifications alter the chromatin architecture, thereby affecting the efficiency of DNA repair. However, how epigenetic modifiers coordinate with the DNA repair machinery to modulate cellular radiosensitivity is relatively unknown. Here, we report that loss of the demethylase ribosomal oxygenase 1 (RIOX1) restores cell proliferation and reduces cell death after exposure to ionizing radiation. Furthermore, RIOX1 depletion enhances homologous recombination (HR) repair but not nonhomologous end-joining (NHEJ) repair in irradiated bone marrow cells and oral mucosal epithelial cells. Mechanistic study demonstrates that RIOX1 removes monomethylation at K491 of cyclic GMP-AMP synthase (cGAS) to release cGAS from its interaction with the methyl-lysine reader protein SAGA complex-associated factor 29 (SGF29), which subsequently enables cGAS to interact with poly(ADP-ribosyl)ated poly(ADP-ribose) polymerase 1 (PARP1) at DNA break sites, thereby blocking PARP1-mediated recruitment of Timeless. High expression of RIOX1 maintains cGAS K491me at a low level, which impedes HR repair and reduces cellular tolerance to ionizing radiation. This study highlights a novel RIOX1-dependent mechanism involved in the non-immune function of cGAS that is essential for the regulation of ionizing radiation-elicited HR repair.