Multifunctional MXene-doped photothermal microneedles for drug-resistant bacteria-infected wound healing.

Skin injuries and drug-resistant bacterial infections pose serious challenges to human health. It is essential to establish a novel multifunctional platform with good anti-infection and wound-healing abilities. In this study, a new MXene-doped composite microneedle (MN) patch with excellent mechanical strength and photothermal antibacterial and ROS removal properties has been developed for infected wound healing. When the MN tips carrying the MXene nanosheets are inserted into the cuticle of the skin, they will quickly dissolve and subsequently release the nanomaterials into the subcutaneous infection area. Under 808 nm NIR irradiation, the MXene, as a "nano-thermal knife", sterilizes and inhibits bacterial growth through synergistic effects of sharp edges and photothermal antibacterial activity. Furthermore, ROS caused by injury and infection can be cleared by MXene-doped MNs to avoid excessive inflammatory responses. Based on the synergistic antibacterial and antioxidant strategy, the MXene-doped MNs have demonstrated excellent wound-healing properties in an MRSA-infected wound model, such as promoting re-epithelialization, collagen deposition, and angiogenesis and inhibiting the expression of pro-inflammatory factors. Therefore, the multifunctional MXene-doped MN patches provide an excellent alternative for clinical drug-resistant bacteria-infected wound management.

Chemokine C-C motif ligand 8 in periodontal ligament during orthodontic tooth movement.

OBJECTIVES: To investigate the roles of chemokine (C-C motif) ligand 8 (CCL8) in periodontal ligament during orthodontic tooth movement (OTM). METHODS: Bioinformatics analyzed 100 genes in human periodontal ligament cells that were most upregulated after 48 hours of mechanical stress, and these genes were classified through GO and KEGG databases. Nickel-titanium closed-coil springs were placed between right first molar and incisors to produce 20 cN of orthodontic force in eight-week-old male SD rats for 1 and 2 days, followed by immunohistochemical staining of CCL8. Human periodontal ligament fibroblasts (hPDLFs) were stimulated by 14% cyclic tension force (Flexcell FX-5000 T Tension System) or hypoxia conditions to mimic OTM for 1 and 2 days, then the resulting CCL8 were examined through ELISA. Scratching assay was performed by treating hPDLFs with different concentrations of CCL8 (1 ng/ml, 10 ng/ml, 100 ng/ml). The migration, proliferation, and adhesion abilities of 100 ng/ml CCL8-treated hPDLFs were also examined. qRT-PCR and western blot detected matrix metalloproteinase 3, periostin, and osteoprotegrin expressions of hPDLFs under 100 ng/ml CCL8. RESULTS: Bioinformatic analysis demonstrated that CCL8 was upregulated after applying mechanical stress for 48 hours. CCL8 secretion showed upregulation after 24 hours of OTM applicationsin vivo and in vitro. CCL8-treated hPDLFs showed significant positive effects on cell proliferation and matrix metalloproteinase 3. It also inhibited periostin and osteoprotegrin expressions. CONCLUSIONS: CCL8 was upregulated in periodontal ligament during initial stage of OTM. Although CCL8 in human periodontal ligaments showed no significant effects on cell migration ability, it did enhance cell proliferation and osteoclastogenesis.

The m6A reader protein YTHDC2 is a potential biomarker and associated with immune infiltration in head and neck squamous cell carcinoma.

BACKGROUND: Increasing evidence has shown that N6-methyladenosine (m6A) RNA methylation regulators have important biological functions in human cancers. However, there are few studies on the value of m6A reader protein YTHDC2 in the diagnosis and tumor-infiltrating of head and neck squamous cell carcinoma (HNSCC). Therefore, it is important to understand the potential clinical value of YTHDC2 in the prognosis and immune infiltration of HNSCC. METHODS: In this study, gene expression profiles and the corresponding clinical information of 270 HNSCC patients were downloaded from the Gene Expression Omnibus (GEO) database. The gene co-expression network was established to verify whether YTHDC2 was related to the prognosis of HNSCC and verified again in the public database. The correlations between YTHDC2 and immune infiltration was investigated via Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). RESULTS: The results showed that YTHDC2 appeared in the blue module related to survival time and survival state and had a close correlation with the prognosis and immune infiltration level of HNSCC in public database. Patients with low expression of YTHDC2 had poor overall survival (OS) and recurrence-free survival (RFS) than those with high expression. In addition, the expression of YTHDC2 was positively correlated with the level of CD4+ T cell subpopulations infiltration in HNSCC. CONCLUSIONS: Through this study, we found that YTHDC2 is a tumor suppressor gene with high expression in normal tissues and low expression in tumor tissues. In addition, YTHDC2 is correlated with the immune infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells in HNSCC, which may become a potential marker for prognosis and immune infiltration of HNSCC.

Application of weighted gene co-expression network analysis to reveal key modules and hub genes in generalized aggressive periodontitis.

OBJECTIVE: The aim of this study was to construct a gene co-expression network to identify key modules and genes in people with generalized aggressive periodontitis. METHODS: We used database GSE79705 to construct a co-expression network by weighted gene co-expression network analysis (WGCNA). In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted. RESULTS: A total of 51 co-expression modules were conducted, darkseagreen1 and blue1 modules were the most significantly related to generalized aggressive periodontitis. Genes in the darkseagreen1 module enriched in affecting cellular response to tumor necrosis factor and vascular endothelial growth factor production, and the blue1 module enriched in the regulation of ion transport, proteinaceous extracellular matrix and neuropeptide binding. Besides, we found that 4 hub genes (SNRPG, MRPL22, MRPS18C and CEP290) played an important role in the occurrence of generalized aggressive periodontitis. CONCLUSION: Through this study, we identified two modules and four hub genes associated with generalized aggressive periodontitis. Besides, 4 hub genes (SNRPG, MRPL22, MRPS18C and CEP290) can be expected to trigger new therapeutic drug development for generalized aggressive periodontitis.