Single-Cell Transcriptomes and Immune Repertoires Reveal the Cell State and Molecular Changes in Pemphigus Vulgaris.

The etiology and pathogenesis of pemphigus vulgaris (PV) entail intricate interactions between immune cells and epithelial cells. However, the specific subtypes of immune cells involved in PV, along with their respective roles, remain elusive. Likewise, the precise functions and mechanisms by which glucocorticoids affect cell types within the disease context require further elucidation. To address these knowledge gaps, we performed 5' single-cell RNA sequencing, combined with V(D)J enrichment on buccal mucosal lesions and peripheral blood samples from treatment-naive patients with PV, in conjunction with post-treatment peripheral blood samples obtained after oral prednisone treatment. Our findings suggest that the IL-1α signaling pathway, myeloid APCs, inflammatory CD8+ resident memory T cells, and dysfunctional CD4+ regulatory T cells are involved in the pathogenesis of PV. Part of these findings were validated by immunohistochemical assays and multiplex immunofluorescence assays. Furthermore, our results highlight the significant impact of prednisone treatment on monocytes and mucosal-associated invariant T cells while revealing a limited effect on CD4+ regulatory T cells. Additionally, we present the CDR3 amino acid sequence of BCR related to PV disease and investigate the characteristics of TCR/BCR clonotypes. In conclusion, our study provides a comprehensive understanding of PV, particularly focusing on the mucosal-dominant type, and sheds light on the effects of glucocorticoids within the PV context. These insights hold promise for the development of new therapeutic strategies in this autoimmune disorder.

Angelicin inhibits cell growth and promotes apoptosis in oral squamous cell carcinoma by negatively regulating DUSP6/cMYC signaling pathway.

Angelicin has been reported to have antitumor effects on many types of cancer. However, few studies on angelicin in oral squamous cell carcinoma (OSCC) have been performed. We performed cell cycle and apoptosis analyses to assess the effect of angelicin on OSCC cells. We conducted RNA-seq studies to reveal differentially expressed genes (DEGs). Dual-specificity phosphatase 6 (DUSP6) and c-MYC were strongly down-regulated differential genes. Silencing RNA (siRNA) was used to knockdown DUSP6. The mouse xenograft model was used to mimic OSCC. Angelicin inhibited OSCC in vitro. We found that DUSP6 interacted with c-MYC. DUSP6 knockdown group and DUSP6 knockdown + angelicin group had similar effects of OSCC cells. Angelicin could reduce tumor formation, DUSP6, and c-MYC expression in vivo. Compared with paclitaxel, the tumor inhibition effect of the two drugs was similar. However, angelicin did not cause weight loss and had lower toxicity. In sum, Angelicin has antitumor effects on OSCC in vitro and vivo by negatively regulating the DUSP6 mediated c-MYC signaling pathway.

Single-cell immune profiling reveals immune responses in oral lichen planus.

Introduction: Oral lichen planus (OLP) is a common chronic inflammatory disorder of the oral mucosa with an unclear etiology. Several types of immune cells are involved in the pathogenesis of OLP. Methods: We used single-cell RNA sequencing and immune repertoire sequencing to characterize the mucosal immune microenvironment of OLP. The presence of tissue-resident memory CD8+ T cells are validated by multiplex immunofluorescence. Results: We generated a transcriptome atlas from four OLP biopsy samples and their paired peripheral blood mononuclear cells (PBMCs), and compared them with two healthy tissues and three healthy PBMCs samples. Our analysis revealed activated tissue-resident memory CD8+ T cells in OLP tissues. T cell receptor repertoires displayed apperant clonal expansion and preferrential gene pairing in OLP patients. Additionally, obvious BCR clonal expansion was observed in OLP lesions. Plasmacytoid dendritic cells, a subtype that can promote dendritic cell maturation and enhance lymphocyte cytotoxicity, were identified in OLP. Conventional dendritic cells and macrophages are also found to exhibit pro-inflammatory activity in OLP. Cell-cell communication analysis reveals that fibroblasts might promote the recruitment and extravasation of immune cells into connective tissue. Discussion: Our study provides insights into the immune ecosystem of OLP, serving as a valuable resource for precision diagnosis and therapy of OLP.

Plasmonic Bi promotes the construction of Z-scheme heterojunction for efficient oxygen molecule activation.

Reactive oxygen species (ROS) are essential to photocatalytic degradation of antibiotics in water. In this work, we prepared Ag3PO4/Bi@Bi4Ti3O12 by simple in-situ reduction method and precipitation method, which improves the ability to capture visible light and increases the activity of photoinduced molecular oxygen activation, resulting in reactive oxygen species (ROS) such as superoxide radicals (•O2-), hydroxyl radicals (•OH), and H2O2. The excellent TC degradation efficiency derive from the SPR effect of the metal Bi on the surface enhances the light absorption intensity, and development of a Z-scheme heterojunction between Ag3PO4 and Bi4Ti3O12 promotes the activation of molecular oxygen. A possible photodegradation mechanism of the as-prepared photocatalyst was proposed. This work provides an insight perspective to the synthesis photocatalysts with molecular oxygen activation for environmental remediation.

Biosafety, Nontoxic Nanoparticles for VL-NIR Photothermal Therapy Against Oral Squamous Cell Carcinoma.

Semiconductor nanocrystals with extraordinary physicochemical and biosafety properties with unique nanostructures have shown tremendous potential as photothermal therapy (PTT) nanosensitizers. Herein, we successfully synthesized chiral molybdenum (Cys-MoO3-x ) nanoparticles (NPs) for overcoming the general limitation on electron energy bands and biotoxicity. The obtained Cys-MoO3-x NPs are selected as an ideal design for the treatment of oral squamous cell carcinoma (OSCC) cells through the decoration of cysteine molecules due to excellent initial photothermal spectral analysis of conductivity and light absorbance. Notably, NPs possess the ability to act as visible light (VL) and near-infrared (NIR) double-reactive agents to ablate cancer cells. By combining photoconductive PTT with hypotoxicity biochemotherapy, the treatment validity of OSCC cancer cells can be improved in vitro by up to 89% (808 nm) and get potential PTT effect under VL irradiation, which intuitively proved that the nontoxic NPs were lethally effective for cancer cells under laser irradiation. Hence, this work highlights a powerful and safe NP platform for NIR light-triggered PTT for use in head and neck cancer (HNC) cells, showing promising application prospects in oral tumor treatment.

[Application of Cochrane systematic reviews in diagnosis and treatment for oral mucosal diseases].

OBJECTIVE: To collect evidence in diagnosis and treatment of oral mucosal diseases. METHODS: The Cochrane library (Issue 3, 2009) was searched to get the full texts of published related Cochrane systematic reviews. The results were summarized for recommendation to dentists. The current status of evidence based medicine in this field was analyzed. RESULTS: Reliable evidence for management of oral submucous fibrosis is still limited; amifostine, hydrolytic enzymes, ice chips and Chinese medicine may be effective in preventing oral mucositis for patients with cancer receiving radiotherapy or chemotherapy; the evidence in treating oral mucositis with allopurinol mouthwash, granulocyte macrophage-colony stimulating factor, immunoglobulin or human placentral extract for patients with cancer receiving treatment is weak and unreliable yet; there is evidence that acyclovir is efficacious in prevention and treatment of herpes simplex virus infections in patients being treated for cancer; there is strong evidence that drugs absorbed or partially absorbed from the gastrointestinal tract prevent oral candidiasis in patients receiving treatment for cancer; relapses and adverse effects are common in using beta carotene, lycopene, vitamin A or retinoids to treat oral leukoplakia; only some weak evidence is provided in using cyclosporines, retinoids, steroids or phototherapy for treating oral lichen planus; the evidence about acyclovir for treating primary herpetic gingivostomatitis is insufficient; there is little research evidence for treatment of burning mouth syndrome. CONCLUSION: It is essential to raise the quality of design and conduction of clinical trials in the field of oral mucosal disease to provide solid bases for systematic review, so that to improve evidence based treatment of these diseases.