Intervention with extracellular matrix metalloproteinase inducer in osteoclasts attenuates periodontitis-induced bone resorption.

Extracellular matrix metalloproteinase inducer (EMMPRIN) plays critical roles in the regulation of inflammation and bone metabolism. The roles of EMMPRIN signaling in osteoclasts are worthy of deep study. The present study aimed to investigate bone resorption in periodontitis through the intervention of EMMPRIN signaling. The distribution of EMMPRIN in human periodontitis was observed. RANKL-induced osteoclast differentiation of mouse bone marrow-derived macrophages (BMMs) were treated with EMMPRIN inhibitor in vitro. Rats with ligation-induced periodontitis were treated with EMMPRIN inhibitor and harvested for microcomputed tomography scanning, histologic observation, immunohistochemistry, and double immunofluorescence analysis. Positive expressions of EMMPRIN could be found in the CD68+-infiltrating cells. Downregulated EMMPRIN restrained osteoclast differentiation of BMMs in vitro, which also inhibited MMP-9 expression (*P < 0.05). In vivo, EMMPRIN inhibitor restrained ligation-induced bone resorption by decreasing tartrate-resistant acid phosphatase-positive osteoclasts. Both EMMPRIN-positive and MMP-9-positive osteoclasts were less common in the EMMPRIN inhibitor groups than in the control groups. Intervention of EMMPRIN signaling in osteoclasts could probably provide a potential therapeutic target for attenuating ligation-induced bone resorption.

Knowledge, attitude, and practice toward self-control of dental plaque among patients with periodontal diseases: a cross-sectional study.

BACKGROUND: The development of periodontal disease is closely linked to individual oral healthcare behaviors. This study aimed to investigate the knowledge, attitude, and practice (KAP) toward the self-control of dental plaque among patients with periodontal diseases. METHODS: This cross-sectional study was conducted at Jinan Stomatological Hospital between July 2022 and September 2022 through a self-administrated questionnaire for patients with periodontal diseases. RESULTS: A total of 563 participants were included. Among them, 147 (26.11%) had gingivitis and 416 (73.89%) had periodontitis. Participants' knowledge, attitude, and practice scores were 8.71 ± 2.81 (range 0-12), 39.82 ± 3.69 (range 10-50), 33.13 ± 5.91 (range 11-55), respectively. The multivariate logistic regression analysis showed that the knowledge [odds ratio (OR) = 1.212, 95% confidence interval (CI): 1.097-1.339, P < 0.001], attitude (OR = 1.132, 95% CI: 1.070-1.198, P < 0.001), occupation, especially in the commercial and service industry (OR = 0.488, 95% CI: 0.221-1.080, P = 0.007), and income of 10,000-20,000 yuan (OR = 0.476, 95% CI: 0.258-0.877, P = 0.017) were independently associated with good practice. CONCLUSIONS: Chinese patients with periodontal diseases demonstrated satisfactory knowledge and attitudes regarding oral hygiene, but the practical aspects need more promotion and training, especially in daily brushing frequency, usage of oral irrigator and interdental brush. Individualized approach should consider patients' knowledge, attitudes, occupation and income level.

Identification of Immune Subtypes for Predicting the Prognosis of Patients in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with poor prognosis and immune response, which plays an important role in tumor progression. Recently, immunotherapies have revolutionized the therapeutic means of malignancies including HNSCC. However, the relationship between immunophenotypes of HNSCC and its clinical response to immune-checkpoint inhibitors remains unclear. We aim to identify molecular subtyping related to distinct immunophenotypes in HNSCC. Consensus clustering algorithm was conducted for subtyping. Immunophenotypes between subtypes were compared according to infiltrating immunocytes, immune reactions, major histocompatibility complex (MHC) family, immunoinhibitory, immunostimulatory and immune scores. The relationship between immunophenotype and genotype was investigated from gene mutation and tumor mutation burden. The potential response of Immune-checkpoint blockade (ICB) therapy was estimated with TIDE and ImmuCellAI algorithms, and immune-checkpoint genes. The immune characteristics were also investigated. Biological functions were annotated by the gene-set enrichment analysis (GSEA) algorithm. Two distinct immune subtypes of HNSCC with different survival outcomes, biological characteristics, immunophenotype, and ICB response were identified. The subtype-1 was featured with better prognosis, more infiltrated immunocytes, stronger immune reaction, higher immune-related gene expression, higher immune-checkpoint gene expression (PD-1, PD-L1, and CTLA-4), and better ICB response. A higher immune response in subtype-1 was also revealed by GSEA. Subtype-1 possessed a higher immune response and more sensitivity to ICB therapy leading to a better prognosis. These findings may shed promising light on the immunotherapy strategy in HNSCC.

Progranulin is highly expressed in patients with chronic periodontitis and protects against experimental periodontitis in rats.

BACKGROUND: The autocrine growth factor progranulin (PGRN) plays a crucial role in the physiological and pathological processes. However, its function in chronic periodontitis (CP) remains unclear. METHODS: Forty-five CP patients and 43 healthy controls were recruited. Expressions of PGRN in gingival biopsies were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry, respectively. The levels of PGRN, tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1ß) in the gingival crevicular fluid (GCF) before and after non-surgical periodontal treatment were quantified by ELISA. In addition, recombinant human PGRN (rhPGRN) or its vehicle was injected into the gingiva of rats with ligature-induced experimental periodontitis to test its influence on the disease process. Local inflammatory cell infiltration and alveolar bone loss were assessed by histomorphometric analysis, and the expression levels of TNF-α and IL-1ß in the gingiva were determined by RT-qPCR and ELISA. RESULTS: PGRN expression was increased in the gingiva and GCF of patients with CP compared with healthy controls. With the decline of periodontal clinical indices, the molar ratio of PGRN to TNF-α in GCF at 1 month after non-surgical treatment was significantly higher than at baseline (35.31 ± 22.09 vs 25.67 ± 16.19, P < 0.01). In rats with experimental periodontitis, local administration of rhPGRN attenuated inflammatory cell infiltration (P < 0.05), inhibited alveolar bone loss (P < 0.05) and decreased TNF-α and IL-1ß levels (both P < 0.01) compared with the vehicle treatment group. CONCLUSION: These findings suggest that progranulin is highly expressed in the gingiva and GCF of patients with CP and protects against experimental periodontitis in rats.

Long noncoding RNA GIHCG enhanced tongue squamous cell carcinoma progression through regulating miR-429.

Long noncoding RNAs play essential roles in cancer development and progression. Here, we tried to investigate the role of GIHCG in the progression and metastasis of tongue squamous cell carcinoma (TSCC). In our study, we showed that that the expression level of GIHCG was upregulated in TSCC tissues and cell lines. In addition, we indicated that high GIHCG expression was positively associated with poor overall survival. Moreover, ectopic expression of GIHCG enhanced TSCC cell cycle, proliferation, and migration. Elevated expression of GIHCG inhibited the miR-429 expression in TSCC cells. We demonstrated that the expression level of miR-429 was lower in TSCC tissues and cell lines. Low miR-429 expression was positively associated with poor overall survival. We then determined the correlation between miR-429 and GIHCG expression levels. A statistically significantly inverse correlation was observed between miR-429 and GIHCG expression levels in TSCC tissues. In addition, overexpression of miR-429 suppressed the TSCC cell cycle, proliferation, and migration. Elevated expression of GIHCG promoted TSCC cell cycle, proliferation, and migration through regulating miR-429 expression. These results suggested that GIHCG increased TSCC progression through negative modulation of miR-429. Our results suggested that GIHCG/miR-429 might play a vital role in TSCC progression.

Long non-coding RNA CASC15 promotes tongue squamous carcinoma progression through targeting miR-33a-5p.

Long non-coding RNAs (lncRNAs) have gained a lot of attention because they participate in several human disorders, including tumors. This study determined the role of LncRNA CASC15 (cancer susceptibility candidate 15) in the development of tongue squamous cell carcinoma (TSCC). Here, we identified that CASC15 expression was upregulated in TSCC samples and cell lines. We showed that overexpression of CASC15 promoted cell proliferation, cycle, and migration in TSCC. In addition, we revealed that miR-33a-5p expression was downregulated in TSCC tissues and cell lines. Moreover, we showed that the expression of CASC15 was negatively related with miR-33a-5p expression in TSCC tissues. Ectopic expression of miR-33a-5p suppressed cell proliferation, cycle, and migration in TSCC. Elevated expression of CASC15 suppressed miR-33a-5p expression and promoted ZEB1 expression in SCC4 cell. Ectopic expression of CASC15 promoted TSCC cell proliferation, cycle, and migration through targeting miR-33a-5p. These results suggested that lncRNA CASC15 and miR-33a-5p might be exploited as new markers of TSCC and were potential treatment targets for TSCC patients.

[Study on lingual mucosa carcinogenesis of C57BL/6 mice induced by 4-nitroquinoline 1-oxide].

OBJECTIVE: This study aimed to induce carcinogenesis of lingual mucosa in C57BL/6 mice by feeding them 4-nitroquinoline 1-oxide (4NQO) solution. METHODS: A total of 85 C57BL/6 mice were randomly divided into distilled water control group (DD group, n=5), 1,2-propylene glycol control group (PG group, n=5), and experimental group (EP group, n= 75). The mice in the experimental group were medially fed in 15 cages. By contrast, the mice in DD, EP, and PG groups were watered with distilled water, 50 mg.L-1 4NQO solution, and 1,2-propylene glycol solution. The mice in EP group were executed every two weeks from week 0, and the mice in the control groups were sacrificed at the 28th week. The mice were weighed. Mucosal lesions were measured by macroscopic observation and histopathologic detection. RESULTS: One mouse in EP group died of unknown reason. The weight of the mice in EP group presented weight loss compared with the mice in DD and PG groups after the 24th week. Seventy-nine macroscopic lesions were observed in the lingual mucosa, oral floor, and upper palatal and buccal mucosa. A total of 70 macroscopic lesions (88.6%) were located in the lingual mucosa. Mucosal lesions changed from simple hyperplasia to squamous cell carcinomas. Well-differentiated squamous cell carcinomas were observed in all mice of EP group by pathological section at the 28th week. No lesion was found in the mice of DD and PG groups. CONCLUSION: The animal model of lingual squamous cell carcinomas was successfully established. The periods from 12th to 16th week and 20th to 28th week were the ideal times for the research on pathogenesis of early and medial-advanced stage during carcinogenesis of squamous cell carcinomas.