Introduction: Psoriasis is a chronic immune-mediated inflammatory skin disease with a complex genetic background, susceptible to psoriatic arthritis as a complication. However, interpretation of genetic associations from bulk tissue analyses is limited by cellular heterogeneity, hindering mechanistic inference. This study aimed to explore cell-type-specific causal regulatory mechanisms between psoriasis and periodontitis. Methods: We integrated psoriasis and periodontitis genome-wide association data with three single-cell expression quantitative trait locus (sc-eQTL) datasets (OneK1K, sc-eQTLGen, and dynamic CD4+ T-cell activation). Two-sample Mendelian randomization (MR) was supplemented by bulk eQTL, plasma protein QTL, and Steiger directionality analyses. Prioritized genes were further examined using single-cell transcriptomics, network-based in silico perturbation, functional enrichment, drug-signature analysis, and molecular docking. Results: Cell-type-resolved MR analyses revealed heterogeneous and context-dependent genetic effects across immune cell subsets, with both concordant and discordant associations between psoriasis and periodontitis. Among the prioritised candidates, LRRC25 showed nominally significant MR associations with both diseases, although these associations were not corrected for multiple testing. Bulk blood-derived eQTL analyses showed consistent inverse associations with both diseases, whereas naive B cell-specific MR analyses showed associations in the opposite direction. Single-cell RNA sequencing showed that LRRC25 expression was predominantly detected in monocytes, whereas only a small proportion of naive B cells expressed LRRC25 . In silico LRRC25 perturbation in monocytes produced concordant transcriptional changes across psoriasis and periodontitis, with FCGR3A identified as a central network hub. Functional enrichment analyses implicated innate immune, type I interferon and Fc receptor-related pathways. Conclusions: LRRC25 emerged as a putative shared immunoregulatory candidate, although evidence varied across molecular levels and immune cell contexts. No statistically significant shared protein-level association was identified. Our findings suggest that bulk eQTL inference may obscure cell-type-specific regulatory signals and highlight the value of single-cell-informed gene prioritization. Further experimental validation is needed.
Introduction Psoriasis is a chronic immune-mediated inflammatory skin disease with a complex genetic background, susceptible to psoriatic arthritis as a complication. However, interpretation of genetic associations from bulk tissue analyses is limited by cellular heterogeneity, hindering mechanistic inference. This study aimed to explore cell-type-specific causal regulatory mechanisms between psoriasis and periodontitis. Methods We integrated psoriasis and periodontitis genome-wide association data with three single-cell expression quantitative trait locus (sc-eQTL) datasets (OneK1K, sc-eQTLGen, and dynamic CD4+ T-cell activation). Two-sample Mendelian randomization (MR) was supplemented by bulk eQTL, plasma protein QTL, and Steiger directionality analyses. Prioritized genes were further examined using single-cell transcriptomics, network-based in silico perturbation, functional enrichment, drug-signature analysis, and molecular docking. Results Cell-type-resolved MR analyses revealed heterogeneous and context-dependent genetic effects across immune cell subsets, with both concordant and discordant associations between psoriasis and periodontitis. Among the prioritised candidates, LRRC25 showed nominally significant MR associations with both diseases, although these associations were not corrected for multiple testing. Bulk blood-derived eQTL analyses showed consistent inverse associations with both diseases, whereas naive B cell-specific MR analyses showed associations in the opposite direction. Single-cell RNA sequencing showed that LRRC25 expression was predominantly detected in monocytes, whereas only a small proportion of naive B cells expressed LRRC25. In silico LRRC25 perturbation in monocytes produced concordant transcriptional changes across psoriasis and periodontitis, with FCGR3A identified as a central network hub. Functional enrichment analyses implicated innate immune, type I interferon and Fc receptor-related pathways. Conclusions LRRC25 emerged as a putative shared immunoregulatory candidate, although evidence varied across molecular levels and immune cell contexts. No statistically significant shared protein-level association was identified. Our findings suggest that bulk eQTL inference may obscure cell-type-specific regulatory signals and highlight the value of single-cell-informed gene prioritization. Further experimental validation is needed.
Introduction and aims: Head and neck squamous cell carcinoma (HNSCC) is a major oral health challenge, and accumulating evidence suggests that microbial dysbiosis may contribute to disease development. However, most previous studies relied on 16S rRNA sequencing, limiting species-level resolution and providing inconsistent microbial signatures across cohorts. This study aimed to characterize HNSCC-associated microbial alterations using genome-resolved metagenomics and identify candidate microbiota-based interventions. Methods: Shotgun metagenomic data from 150 oral and faecal samples spanning an in-house case–control cohort and two public datasets were integrated and analysed using a unified bioinformatics pipeline. Microbial diversity, differential biomarkers, co-occurrence networks, and species-level genome bins were analysed. Candidate probiotic strains were predicted using metaProbiotics and further evaluated in a CAL27 zebrafish xenograft model. Results: Faecal communities showed stronger disease-associated restructuring than oral communities, with reduced observed richness and significant Bray–Curtis separation, whereas oral community differences were not significant. Integration of LEfSe and random forest identified eleven faecal consensus markers, including control-enriched Roseburia faecis, Phocaeicola vulgatus , and Bifidobacterium longum , and four cancer-enriched oral markers, including reproducible Capnocytophaga sputigena . Microbial networks were consistently less connected in HNSCC across both niches. Among 990 dereplicated species-level genome bins, Bifidobacterium represented the dominant high-confidence probiotic genus. In vivo validation showed that B. longum and the induction chemotherapy component docetaxel, cisplatin, and 5-fluorouracil (TPF) reduced tumour burden and inflammatory/angiogenic responses, while combination treatment modulated macrophage-associated migration and partially restored microbial network connectivity. Conclusion: Genome-resolved metagenomic profiling revealed distinct oral and gut microbial features associated with HNSCC and identified B. longum as a candidate adjunctive probiotic intervention requiring further mammalian and clinical validation. Clinical relevance: This study provides microbial biomarkers and candidate probiotic strategies that may support future microbiome-based risk assessment and adjunctive management of HNSCC in oral healthcare settings.
Introduction and aims Head and neck squamous cell carcinoma (HNSCC) is a major oral health challenge, and accumulating evidence suggests that microbial dysbiosis may contribute to disease development. However, most previous studies relied on 16S rRNA sequencing, limiting species-level resolution and providing inconsistent microbial signatures across cohorts. This study aimed to characterize HNSCC-associated microbial alterations using genome-resolved metagenomics and identify candidate microbiota-based interventions. Methods Shotgun metagenomic data from 150 oral and faecal samples spanning an in-house case–control cohort and two public datasets were integrated and analysed using a unified bioinformatics pipeline. Microbial diversity, differential biomarkers, co-occurrence networks, and species-level genome bins were analysed. Candidate probiotic strains were predicted using metaProbiotics and further evaluated in a CAL27 zebrafish xenograft model. Results Faecal communities showed stronger disease-associated restructuring than oral communities, with reduced observed richness and significant Bray–Curtis separation, whereas oral community differences were not significant. Integration of LEfSe and random forest identified eleven faecal consensus markers, including control-enriched Roseburia faecis, Phocaeicola vulgatus, and Bifidobacterium longum, and four cancer-enriched oral markers, including reproducible Capnocytophaga sputigena. Microbial networks were consistently less connected in HNSCC across both niches. Among 990 dereplicated species-level genome bins, Bifidobacterium represented the dominant high-confidence probiotic genus. In vivo validation showed that B. longum and the induction chemotherapy component docetaxel, cisplatin, and 5-fluorouracil (TPF) reduced tumour burden and inflammatory/angiogenic responses, while combination treatment modulated macrophage-associated migration and partially restored microbial network connectivity. Conclusion Genome-resolved metagenomic profiling revealed distinct oral and gut microbial features associated with HNSCC and identified B. longum as a candidate adjunctive probiotic intervention requiring further mammalian and clinical validation. Clinical relevance This study provides microbial biomarkers and candidate probiotic strategies that may support future microbiome-based risk assessment and adjunctive management of HNSCC in oral healthcare settings.
Background The periosteal vertical mattress suture (PVMS) technique can stabilize grafts through soft-tissue tension during guided bone regeneration (GBR), but its influence on level-specific postoperative graft behaviour remains uncertain. This study evaluated whether PVMS was associated with level-specific graft stability. Methods This study retrospectively reviewed 49 patients (77 implant sites) treated with GBR in the maxillary anterior esthetic zone. The Suture Group received GBR with PVMS (n = 23), whereas the Non-Suture Group received GBR without membrane fixation (n = 26). Cone-beam computed tomography images were assessed preoperatively (T0), immediately postoperatively (T1), and at postoperative follow-up (T2; 4.5–8.0 months). Linear mixed-effects models examined dimensional changes at 1, 3, 5, and 7 mm, accounting for measurements nested within sites and patients; restricted cubic splines explored the nonlinear relationship between immediate horizontal augmentation and its retention rate. Results Overall augmentation was similar between groups, but the model identified a significant level-dependent pattern (P = .008). The Suture Group showed greater mean retained horizontal augmentation in the apical region, whereas the Non-Suture Group showed greater mean retention at the coronal 1-mm level. After baseline-width adjustment, the group-by-level interaction remained significant (P = .003), but direct between-group contrasts at individual levels were not significant. Immediate graft volume gain correlated with postoperative graft volume reduction in the Non-Suture Group (P < .001), but not significantly in the Suture Group (P = .097); the between-group correlation comparison was nonsignificant (P = .055). Conclusion PVMS was associated with a level-dependent pattern of postoperative graft stability during early healing, rather than a demonstrated overall volumetric benefit. Lower coronal and higher apical mean retention should both be considered when interpreting the postoperative alveolar contour. Clinical relevance: These findings can inform level-specific augmentation planning with PVMS, emphasizing coronal contour preservation to support implant esthetics in the maxillary anterior region.
