Relationship between circulating senescence-associated secretory phenotype levels and severity of type 2 diabetes-associated periodontitis: A cross-sectional study.

BACKGROUND: Senescence-associated secretory phenotype (SASP) has recently been found to drive comorbid diabetes and periodontitis by inducing a chronic, low-degree inflammatory state. Here, we sought to explore the relationship between circulating SASP and the severity of type 2 diabetes-associated periodontitis (DP). METHODS: Eighty patients (middle-aged periodontitis, M-P group; aged periodontitis, A-P group; M-DP group; and A-DP group; n = 20) provided gingival epithelium, serum, and periodontal clinical parameters. Circulating levels of 12 DP-related SASP factors were analyzed by immunoassay. Correlation between periodontal clinical parameters and circulating SASP levels was analyzed by Spearman's rank correlation coefficient and back propagation artificial neural network (BPNN). Senescence markers (p16, p21, and HMGB1) in gingiva were determined by immunofluorescence assay. RESULTS: M-DP group had increased serum levels of twelve SASP factors compared with the M-P group (p < 0.5). Serum levels of IL-6, IL-4, and RAGE were higher in the A-DP group than the A-P group (p < 0.5). The circulating concentrations of certain SASP proteins, including IL-1ß, IL-4, MMP-8, OPG, RANKL, and RAGE were correlated with the clinical parameters of DP. BPNN showed that serum SASP levels had considerable predictive value for CAL of DP. Additionally, the DP group had higher expressions of p16, p21, and cytoplasmic-HMGB1 in the gingiva than the P group (p < 0.5). CONCLUSIONS: Significantly enhanced circulating SASP levels and aggravated periodontal destruction were observed in patients with DP. Importantly, a non-negligible association between serum SASP levels and the severity of DP was found.

[Uprighting a mesially tilted mandibular second molar by using a dental implant as anchorage: a case report].

After tooth has been removed for a long time, adjacent teeth may tilt to occupy the edentulous space, leading to a break in the occlusal 3D equilibrium and a lack of restorative space. This case report presents a mandibular second molar uprighting with anchorage from a dental implant.

The risk of moderate-to-severe post-operative pain following the placement of dental implants.

In recent years, the implant-supported dentures have risen rapidly, and thus, more attention was paid to post-operative pain, following dental implantation. To explore risk factors and establish as well as validate a risk prediction model for moderate-to-severe post-operative pain following dental implantation. A observational study of 352 patients with 563 implants was carried out. The following candidate predictors were collected: age, gender, pain sensitivity, anxiety, pain expectation, operator experience, position, length and number of placed implants, duration of surgery and surgery procedures. The outcome was the presence of moderate-to-severe post-operative pain within the 24 hours post-surgery. Multivariate logistic regression in combination with bootstrapping techniques was used to explore independent risk factors and establish a prediction model. The mean pain intensity score was 4.21 within 24 hours post-operatively, while the incidence of moderate-to-severe pain was 61.9%. Independent risk factors of moderate-to-severe post-operative pain were flap surgery, surgical template, the interaction between anxiety state and pain sensitivity, the interaction between pain sensitivity and pain expectation and the interaction between implant length and immediate implant. The area under the receiver operator characteristic curve was 0.72. The model's sensitivity was 75.7%, and the specificity was 64.2%. The model reliability was good (Nagelkerke's R2 0.226). The risk factors and the prediction model (needs further improvement) can help dentists to identify patients at increased risk of moderate-to-severe post-operative pain following dental implantation.

Chimeric 5/35 adenovirus-mediated Dickkopf-1 overexpression suppressed tumorigenicity of CD44⁺ gastric cancer cells via attenuating Wnt signaling.

BACKGROUND: Gastric cancer stem cells (CSCs), which require activation of Wnt signaling to maintain their self-renewal and tumorigenicity, are proposed to be critical targets for effective therapy of gastric carcinomas. Gene therapies that are delivered by adenovirus of serotype 5 (Ad5) or chimeric 5/35(Ad5/35) adenovirus have shown promise for treating various cancers. Here we aimed to develop a gene therapy strategy that targeted gastric CSCs (CD44⁺ cells). METHODS: CD44⁺ cells were isolated by fluorescence activated cell sorting from both primary gastric cancer cells and cell lines. Expression of adenovirus receptors was examined in CD44⁺ and CD44⁻ cells. A potent Wnt antagonist Dickkopf-1 (DKK1) was delivered into CD44⁺ cells using Ad5/35 (Ad5/35-DKK1). The therapeutic outcomes were evaluated. RESULTS: Expression of Coxsakievirus adenovirus receptor for Ad5 was significantly reduced, while abundance of CD46, the receptor for Ad5/35, was slightly higher in CD44⁺ cells. Accordingly, CD44⁺ cells were sensitive to Ad5/35 infection, but not to Ad5. Ad5/35-DKK1 introduced DKK1 into CD44⁺ cells and deactivated endogenous Wnt/ß-catenin signaling efficiently. Overexpression of DKK1 inhibited survival, anchorage-independent colony formation, and invasion of CD44⁺ cells, which were restored by a GSK-3 specific inhibitor BIO-acetoxime. More importantly, introduction of DKK1 abrogated the tumorigenicity of CD44⁺ cells in vivo. However, Ad5/35-DKK1 only showed minimal cytotoxicity to normal tissue-derived cells, L-02 and GES-1. CONCLUSIONS: We developed, for the first time, a novel Ad5/35-DKK1-based approach to abrogate Wnt signaling in CSCs and demonstrated that gastric CSC-targeting gene therapy was effective in preclinical experiments.