Emerging role of METTL3 in inflammatory diseases: mechanisms and therapeutic applications.

Despite improvements in modern medical therapies, inflammatory diseases, such as atherosclerosis, diabetes, non-alcoholic fatty liver, chronic kidney diseases, and autoimmune diseases have high incidence rates, still threaten human health, and represent a huge financial burden. N6-methyladenosine (m6A) modification of RNA contributes to the pathogenesis of various diseases. As the most widely discussed m6A methyltransferase, the pathogenic role of METTL3 in inflammatory diseases has become a research hotspot, but there has been no comprehensive review of the topic. Here, we summarize the expression changes, modified target genes, and pathogenesis related to METTL3 in cardiovascular, metabolic, degenerative, immune, and infectious diseases, as well as tumors. In addition to epithelial cells, endothelial cells, and fibroblasts, METTL3 also regulates the function of inflammation-related immune cells, including macrophages, neutrophils, dendritic cells, Th17 cells, and NK cells. Regarding therapeutic applications, METTL3 serves as a target for the treatment of inflammatory diseases with natural plant drug components, such as emodin, cinnamaldehyde, total flavonoids of Abelmoschus manihot, and resveratrol. This review focuses on recent advances in the initiation, development, and therapeutic application of METTL3 in inflammatory diseases. Knowledge of the specific regulatory mechanisms involving METTL3 can help to deepen understanding of inflammatory diseases and lay the foundation for the development of precisely targeted drugs to address inflammatory processes.

Porphyromonas gingivalis exacerbates ulcerative colitis via Porphyromonas gingivalis peptidylarginine deiminase.

Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalis strain in which the PPAD gene was deleted (Δppad) and a Δppad strain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad, or comΔppad twice a week for the entire 40 days (days 0-40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31-40). P. gingivalis and comΔppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppad increased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Δppad, or comΔppad with T lymphocytes in vitro and found that P. gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalis exacerbated the severity of UC in part via PPAD.

Composition and function of oral microbiota between gingival squamous cell carcinoma and periodontitis.

OBJECTIVES: Previous studies have proved that periodontitis is an independent risk factor of oral squamous cell carcinoma (OSCC) epidemiologically. Along with the important role of microbiota in the cancer process and the specific anatomical position, our study explored the microbial composition and functions in periodontitis and gingival squamous cell carcinoma (GSCC). MATERIALS AND METHODS: GSCC patients (n = 10), matched periodontitis patients (n = 15), and healthy individuals (n = 15) were recruited. Saliva, subgingival plaque, tongue dorsum, buccal mucosa, cancerous tissue, and paracancerous tissue samples were collected. 16S rDNA amplicon sequencing and functional prediction were applied for the taxonomic analysis. RESULTS: Periodontal pathogens occupied 46% in GSCC. Besides, the mutual operational taxonomy unites (OTU) generated from the subgingival plaque occupied 38.36% and 44.13% from saliva. Fusobacterium, Peptostreptococcus, and Prevotella were more abundant in cancerous tissues, while Streptococcus, Neisseria, and Haemophilus were more enriched in saliva or soft mucosa. PCoA exhibited similar cluster between tongue dorsum and saliva in GSCC. GSCC showed lower richness than periodontitis. In saliva and subgingival plaque, Atopobium was more prevalent in GSCC than periodontitis and controls in descending order. Lipopolysaccharide (LPS) biosynthesis increased in subgingival plaque of GSCC compared with the other two groups. CONCLUSION: Periodontal pathogens were abundant in GSCC. Cancerous tissues harbor enriched periodontal pathogens while saliva or soft mucosa harbored more periodontal health related bacteria. A high level of Atopobium in saliva and LPS biosynthesis have the potential for increasing the risk of suffering from GSCC in individuals with periodontitis, which needs more evidence to clarify it.

Ran promotes the proliferation and migration ability of head and neck squamous cell carcinoma cells.

HNSCC is an aggressive tumor that often recurrence and metastasis. Although the treatment of HNSCC has improved over the past few decades, it is easy to recurrence even after comprehensive treatment. Ran is a small Ras-related GTPase belonging to the Ras superfamily. Recently, Ran has been proven to be an important oncogene involved in the metastatic progression of many human cancers. But there is seldom research on HNSCC about Ran. This study revealed the relationship between Ran expression and HNSCC characteristics, investigated the expression and role of Ran in HNSCC tissues and cells by means of immunohistochemistry, qRT-PCR, CCK-8, FCM and transwell migration assays. The results indicated that HNSCC tissues had significantly higher Ran expression than adjacent non-tumor tissues. The overall survival rate was significantly lower in patients with Ran-positive tumors than in those with Ran-negative tumors. Moreover, Ran was positively correlated with tumor grade, lymph node metastasis and recurrence. Ran was also high expressed in the HNSCC cell lines (PCI-37B and SCC9) and down regulated of Ran could evidently inhibit their proliferation, migration and down-regulate of Met protein. In conclusion, our findings suggested Ran could promote the proliferation and migration ability of HNSCC cells. Ran may play an important role in the development of HNSCC and may serve as a novel prognostic indicator of HNSCC.

The prevalence rate of periodontal pathogens and its association with oral squamous cell carcinoma.

Mounting evidence suggests a causal relationship between specific bacterial infections or microbial compositions and the development of certain malignant neoplasms. In this study, we performed research through 16S rRNA amplicon sequencing, qPCR and fluorescence in situ hybridization to certify the relationship between periodontal pathogens and oral squamous cell carcinoma (OSCC). Subgingival plaque, cancer and paracancerous tissues from 6 patients with OSCC were selected for mapping bacterial profiles by 16S rRNA amplicon sequencing. The research showed that periodontal pathogens were enriched in cancer and paracancerous tissues, while the bacterial profiles were similar between the cancer tissues and subgingival plaque. Furthermore, the relative abundance of Porphyromonas gingivalis, Fusobacterium nucleatum and Streptococcus sanguinis was detected in 61 cancer tissues, paracancerous tissues and subgingival plaque samples and in 30 normal tissues by qPCR. The results revealed that P. gingivalis and F. nucleatum existed at higher levels in cancer tissue than in normal tissues and were correlated with subgingival plaques. P. gingivalis was detected using a special oligonucleotide probe in 60.7% of OSCC tissues, 32.8% of paracancerous tissues and 13.3% of normal tissues. Relevance analysis showed that P. gingivalis infection was positively associated with late clinical staging, low differentiation and lymph node metastasis in patients with OSCC, which was accompanied by deeper periodontal pockets, severe clinical attachment loss and loss of teeth. This study revealed that there might be a close relationship between oral microorganisms, particularly periodontal pathogens, and OSCC, which might enrich the pathogenesis of oral squamous carcinoma.

[Effectiveness of Nd:YAG laser with non-surgical periodontal therapy on improvement of periodontitis: meta analysis].

PURPOSE: To compare the effects of premolars restored with 2 different types of fiber post systems, so as to provide experience for restoration of residual crown of premolars. METHODS: Fifty-three residual crowns of premolar restored with fiber post systems were collected, and randomly divided into 2 groups: parallel fiber post group and double taper fiber post group. Repairing effect and operation difficulty were compared. The data was analyzed with SPSS 13.0 software package. RESULTS: There was no significant difference in success rate between the 2 groups, four complications occurred in parallel fiber post group and one in double taper fiber post group. CONCLUSIONS: The success rate between parallel fiber post groups and double taper fiber post group was not different, but the complication in double taper fiber post group is lower than parallel fiber post group.

Effects of different factors influencing clinical compliance of Chinese patients with chronic periodontitis.

OBJECTIVES: The aims of this study were to determine the relationship between compliance in patients with chronic periodontitis and the efficacy of nonsurgical periodontal treatment as well as to investigate the factors that influence the compliance of patients with chronic periodontitis. These aims may be useful for determining the prognosis and improving the efficacy of treatment. METHOD AND MATERIALS: Four hundred patients with chronic periodontitis were classified into three groups: the complete compliance group (S1), the erratic compliance group (S2), and the failing compliance group (S3). The patients who were in group S1 received supportive periodontal therapy (SPT) on time: they presented for their appointments within 2 months of the scheduled date; the patients who missed their appointments by more than 2 months or who completely missed a return visit one or more times, were placed in group S2; and the patients who never returned to receive SPT were assigned to group S3. They completed a questionnaire about compliance and underwent a clinical periodontal examination. SPSS 13.0 was used for the statistical analysis. RESULTS: Groups S2 (49.4%) and S3 (34.1%) were significantly different from group S1 (87.0%) (P < .05) in their understanding that periodontal disease is always associated with other diseases. The analysis of severe pain during the treatment revealed significant differences (P < .05) between group S1 (22.2%) and group S3 (39.9%). Awareness of chronic periodontitis and comfort during treatment are important factors influencing patient compliance. The distance of the patient's residence from the hospital, working hours, and attitudes of family members also affect patient compliance. CONCLUSION: Doctors should educate patients about oral health and manage their patients' comfort as much as possible during treatment, thereby enhancing patient compliance and achieving better treatment efficacy.