Low-level laser therapy alleviates periodontal age-related inflammation in diabetic mice via the GLUT1/mTOR pathway.

Diabetes mellitus (DM) is a chronic age-related disease that was recently found as a secondary aging pattern regulated by the senescence associated secretory phenotype (SASP). The purpose of this study is to detect the potential efficacy and the specific mechanisms of low-level laser therapy (LLLT) healing of age-related inflammation (known as inflammaging) in diabetic periodontitis. Diabetic periodontitis (DP) mice were established by intraperitoneal streptozotocin (STZ) injection and oral P. gingivalis inoculation. Low-level laser irradiation (810 nm, 0.1 W, 398 mW/cm2, 4 J/cm2, 10 s) was applied locally around the periodontal lesions every 3 days for 2 consecutive weeks. Micro-CT and hematoxylin-eosin (HE) stain was analyzed for periodontal soft tissue and alveolar bone. Western blots, immunohistochemistry, and immunofluorescence staining were used to evaluate the protein expression changes on SASP and GLUT1/mTOR pathway. The expression of aging-related factors and SASP including tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 were reduced in periodontal tissue of diabetic mice. The inhibitory effect of LLLT on GLUT1/mTOR pathway was observed by detecting the related factors mTOR, p-mTOR, GLUT1, and PKM2. COX, an intracytoplasmic photoreceptor, is a key component of the anti-inflammatory effects of LLLT. After LLLT treatment a significant increase in COX was observed in macrophages in the periodontal lesion. Our findings suggest that LLLT may regulate chronic low-grade inflammation by modulating the GLUT1/mTOR senescence-related pathway, thereby offering a potential treatment for diabetic periodontal diseases.

Hyperglycaemia aggravates periodontal inflamm-aging by promoting SETDB1-mediated LINE-1 de-repression in macrophages.

AIM: To explore whether hyperglycaemia plays a role in periodontal inflamm-aging by inducing phenotypical transformation of macrophages, as well as the potential mechanism via SET domain-bifurcated histone lysine methyltransferase 1 (SETDB1). MATERIALS AND METHODS: A hyperglycaemic mouse model was established using streptozotocin injection. The alveolar bone was analysed using micro-computed tomography. Periodontal inflamm-aging was detected using western blotting, quantitative real-time PCR and immunohistochemical analysis. In vitro, RAW 264.7 macrophages were incubated with various doses of glucose. siRNA or overexpression plasmids were used to determine the regulatory mechanism of SETDB1 in macrophage senescence and inflamm-aging under hyperglycaemic conditions. Expression and distribution of SETDB1 and long interspersed element 1 (LINE-1) in gingival tissues of patients with or without diabetes were detected using immunofluorescent staining. RESULTS: SETDB1 expression in the periodontal tissues of patients and mice with diabetes was down-regulated compared with that in non-diabetic controls. SETDB1 deficiency induced senescence-like phenotypical changes in macrophages, which aggravated periodontal inflamm-aging in diabetic mice. Furthermore, metformin treatment rejuvenated SETDB1 activity and alleviated the hyperglycaemia-induced periodontal inflamm-aging. CONCLUSIONS: The findings of this study show that SETDB1 regulates senescence-like phenotypical switching of macrophages and is a potential candidate for the treatment of diabetes-induced periodontal inflamm-aging.

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.

Biological Functions of Diallyl Disulfide, a Garlic-Derived Natural Organic Sulfur Compound.

Garlic is widely accepted as a functional food and an excellent source of pharmacologically active ingredients. Diallyl disulfide (DADS), a major bioactive component of garlic, has several beneficial biological functions, including anti-inflammatory, antioxidant, antimicrobial, cardiovascular protective, neuroprotective, and anticancer activities. This review systematically evaluated the biological functions of DADS and discussed the underlying molecular mechanisms of these functions. We hope that this review provides guidance and insight into the current literature and enables future research and the development of DADS for intervention and treatment of multiple diseases.

Effect of adjunctive diode laser in the non-surgical periodontal treatment in patients with diabetes mellitus: a systematic review and meta-analysis.

This study aimed to systematically review and analyze the present randomized clinical trials (RCTs) regarding the clinical efficacy of a diode laser (DL) adjuvant to scaling and root planning (SRP) in patients with chronic periodontitis (CP) who have diabetes mellitus (DM). Five databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trails, Web of Science, and Chinese BioMedical Literature Databases) were searched. A meta-analysis was implemented to evaluate periodontal parameters including probing depth (PD) and clinical attachment level (CAL) as primary outcomes. Hemoglobin A1c (HbA1c), plaque index (PI), and the gingival index (GI) were also observed as secondary outcomes. Independent scanning of 239 papers resulted in 9 RCTs. Moderate evidence demonstrated that the test groups showed significant benefits for PD reduction, CAL gain, and HbA1c reduction after 3 and 6 months. Significant differences in PI and GI reduction were not found except for GI reduction within 1 month. The collective evidence suggested that the DL with SRP had significant improvements in clinical results compared to SRP alone. Based on our results, the DL could be a recommended therapy for patients with CP who have DM.

Efficacy of adjunctive photodynamic therapy and lasers in the non-surgical periodontal treatment: A Bayesian network meta-analysis.

BACKGROUND: Photodynamic therapy (PDT) and lasers have been widely applied in non-surgical treatments in recent decades; however, their efficacy is not known. The objective of this study was to compare adjunctive PDT, different lasers, and scaling and root planning (SRP) in the management of chronic periodontitis. METHODS: Randomized clinical trials (RCTs) assessing adjunctive PDT, different lasers, and SRP were identified. Relevant data were extracted, and the quality and risk of bias were evaluated. Network meta-analyses were performed to analyze clinical attachment level (CAL) outcomes. RESULTS: Forty-four studies, including 10 types of adjuncts, were included. PDT + SRP and PDT + diode laser (DL)+SRP were significantly more efficient than SRP at the 3-month and 6-month follow-up. Adjunctive potassium-titanyl-phosphate (KTP) laser showed significantly more CAL gains than SRP at 6 months. The most effective adjunctive treatment at 3 months was PDT + DL (60 %) and at 6 months was KTP laser (71 %). CONCLUSIONS: PDT + DL + SRP and PDT + SRP were found to be preferentially recommended methods. KTP + SRP was significantly superior to SRP at the 6-month follow-up. However, further investigations are necessary.