ABSTRACT
Objective: The head and neck squamous cell carcinomas (HNSCCs) have higher incidence rates in men, but the reasons are still obscure. This study aimed to investigate the sex-specific gene expression patterns and predict the regulatory mechanisms. Design: Data including clinical, survival, RNA-seq, miRNA, and methylation information were derived from The Cancer Genome Atlas (TCGA). A total of 131 paired male and female cases were included based on propensity score matching. We concentrated on the prognostic values of the sex-specific pathways enriched by differentially expressed genes (DEGs) and predicted the potential regulatory mechanisms from immune cell infiltration, ceRNA regulatory network, methylation, and differential coexpression analysis. Results: Compared with females, males exhibited a lower activity of immune-related functions and higher activities of mitochondrial and ubiquitination functions. The pathway activities were associated with the prognosis of males but less relevant to females. We extracted eight pathways with sex-biased survival patterns, of which five were about down-regulated immune functions, and three were up-regulated pathways (GTP biosynthetic, DNA polymerase, and spliceosomal complex assembly). The five immune pathways were moderately or strongly correlated with the proportion of macrophages. We identified six over-expressed lncRNAs that might be involved in the regulation of the three up-regulated pathways. These lncRNAs exhibited a lower methylation density in males, which might account for their over-expression. Conclusions: For HNSCCs, males were characterized by immunosuppression. It was a sign of unfavorable prognosis and might be associated the proportion of macrophages. LncRNAs and methylation might be involved in the regulation of these pathways.
ABSTRACT
Even though China Antarctic medical care has made huge progress, dental care has always been a neglected area. Dental health is well-known to be closely related with life quality and work efficiency. Hence, knowing the dental care situation there and providing ways to improve are urgently needed. We choose doctors who worked in China Antarctic station as a window to see the whole picture by sending questionnaire. The results showed dental visits ranked second high, the ratio of doctors who got pre-departure dental knowledge education and screen is low. What is worse, none of them got any after-departure dental check. Their dental knowledge is not as good as we expect, and they were troubled by dental problems in Antarctic. Interestingly, most dental problems were treated by non-dentist with no essential equipment, but 2/3 of them were satisfied with the outcome. As for the dental-related diet and behaviour, snacks eating and alcohol drinking are the strongest predictors of dental pain and gum problem. Those findings are crucial to Antarctic dental care and research.
Subject(s)
Alcohol Drinking , Medical Staff , Humans , Antarctic Regions , China , Dental CareABSTRACT
BACKGROUND: Protein arginine methyltransferase 5 (PRMT5) catalyzes the methylation of arginine residues in multiple proteins. Recent reports have highlighted the anti-inflammatory role of PRMT5. Dendritic cells (DCs) are well-known professional antigen-presenting cells that are crucial for immune response initiation. However, whether PRMT5 participates in DC immunity processes is unknown. METHODS: In an in vitro experiment, a PRMT5 inhibitor (EPZ015666) was used to inhibit PRMT5 expression, and lipopolysaccharide (LPS) stimulation was applied to mimic the inflammation context. Proinflammatory cytokine production, interferon-stimulated genes (ISGs), costimulatory molecules, major histocompatibility complex (MHC) expression and DC metabolism were measured following PRMT5 inhibition and LPS stimulation. In an in vivo study, we first tested PRMT5 mRNA and protein expression in a BALB/c mouse ligature-induced periodontitis model. Then, we evaluated changes in periodontal tissue and DC migration to cervical lymph nodes after local treatment with the PRMT5 inhibitor. RESULTS: The in vitro results revealed that PRMT5 inhibition attenuated DC activation and maturation by inhibiting the expression of proinflammatory cytokines, ISGs, costimulatory molecules, and MHC induced by LPS stimulation. We also found that inhibition of PRMT5 blocked the DC metabolic switch to glycolysis. In the in vivo study, we found that PRMT5 inhibition reversed the severity of the lesions and slowed the migration of DCs to cervical lymph nodes. CONCLUSIONS: The results show a critical role of PRMT5 in the control of DC activation through inhibition of the metabolic switch and indicate that PRMT5 is a promising therapeutic target in periodontitis.
ABSTRACT
In the inflamed microenvironment of peri-implantitis, limited osteogenesis on the implant surface impedes well-established reosseointegration using current clinical therapies. MicroRNAs (miRNAs) function as potent molecular managers that may simultaneously regulate multiple endogenous processes such as inflammation and osteogenesis. The delivery of miRNAs may provide a way to effectively treat some diseases. In this study, we showed that miR-27a was differentially downregulated in samples from a canine peri-implantitis model. We found that overexpressing miR-27a positively regulated osteogenesis-angiogenesis coupling by ameliorating the TNF-α inhibition of bone formation in vitro. Mechanistically, we identified Dickkopf2 (DKK2) and secreted frizzled related protein 1 (SFRP1) as two essential direct miR-27a targets that were osteogenic and angiogenic. Furthermore, we constructed a miR-27a-enhanced delivery system to repair the bone defect around implants in a canine peri-implantitis model. The results demonstrated that the miR-27a-treated group could optimize new bone formation and reosseointegration in vivo. Our assay provides evidence that this strategy exerts therapeutic effects on peri-implantitis, suggesting that it represents a feasible method to maintain the stability and masticatory function of dental implants. © 2018 American Society for Bone and Mineral Research.
Subject(s)
Dental Implants , Down-Regulation , Intercellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/metabolism , MicroRNAs/metabolism , Osteogenesis , Peri-Implantitis , Animals , Dogs , Male , Osseointegration , Peri-Implantitis/metabolism , Peri-Implantitis/pathology , Peri-Implantitis/therapyABSTRACT
Peri-implantitis, which is characterized by dense inflammatory infiltrates and increased osteoclast activity, can lead to alveolar bone destruction and implantation failure. miRNAs participate in the regulation of various inflammatory diseases, such as periodontitis and osteoporosis. Therefore, the present study aimed to investigate the differential expression of miRNAs in canine peri-implantitis and to explore the functions of their target genes. An miRNA sequence analysis was used to identify differentially expressed miRNAs in peri-implantitis. Under the criteria of a fold-change >1.5 and P<0.01, 8 up-regulated and 30 down-regulated miRNAs were selected for predictions of target genes and their biological functions. Based on the results of Gene Ontology (GO) and KEGG pathway analyses, these miRNAs may fine-tune the inflammatory process in peri-implantitis through an intricate mechanism. The results of quantitative real-time PCR (qRT-PCR) revealed that let-7g, miR-27a, and miR-145 may play important roles in peri-implantitis and are worth further investigation. The results of the present study provide insights into the potential biological effects of the differentially expressed miRNAs, and specific enrichment of target genes involved in the mitogen-activated protein kinase (MAPK) signaling pathway was observed. These findings highlight the intricate and specific roles of miRNAs in inflammation and osteoclastogenesis, both of which are key aspects of peri-implantitis, and thus may contribute to future investigations of the etiology, underlying mechanism, and treatment of peri-implantitis.
Subject(s)
MicroRNAs/genetics , Peri-Implantitis/genetics , Animals , Bone Resorption/etiology , Bone Resorption/genetics , Dental Implants/adverse effects , Disease Models, Animal , Dogs , Gingiva/pathology , Male , Mitogen-Activated Protein Kinases/genetics , Osteoclasts/physiology , Osteogenesis/physiology , Stomatitis, Denture/etiology , Stomatitis, Denture/geneticsABSTRACT
miRNAs play a number of roles in bone, including mediating the pathological effects of inflammation. Here, we found that miR-33a-5p expression was significantly increased after TNF-α treatment during BMP-2-induced osteogenic differentiation of hBMSCs. Luciferase reporter assays and western blotting demonstrated that special AT-rich sequence-binding protein 2 (SATB2) is a target of miR-33a-5p. Moreover, we show that BMP-2 induces SATB2 expression by interacting with SATB2 directly via the BMP-2-RUNX2 pathway. However, TNF-α first decreases SATB2 expression by inhibiting miR-33a-5p degradation. We thus conclude that miR-33a-5p plays a central role in this complex regulatory network. These findings will help to understand the regulatory role of miR-33a-5p in the inflammatory process.