Bi-directional two-sample Mendelian randomization identifies causal association of depression with temporomandibular disorders.

BACKGROUND: Depression and anxiety have been suggested to be associated with temporomandibular disorders (TMD) in observational studies. However, the causal association and the direction in the relationship between depression/anxiety and TMD remain unknown. OBJECTIVES: This study investigated the potential causal relationship between depression/anxiety and TMD with two-sample bi-directional Mendelian randomization (MR). METHODS: Summary statistics of depression (N = 500 199), anxiety disorder (N = 17 310) and TMD (N = 195 930) were sourced from large-scale genome-wide association studies (GWAS). The primary Mendelian randomization (MR) estimation employed the inverse-variance weighted meta-analysis (IVW). Additional MR sensitivity methods and multivariate MR (MVMR) were applied to address pleiotropy. RESULTS: IVW results indicated a causal effect of genetically predicted depression on TMD (OR = 1.887, 95% CI = 1.504-2.367, p < .001), which was supported by other sensitivity MR approaches. MVMR results suggested that the negative effect of depression on TMD persisted after conditioning on other potential confounders. The association of anxiety disorder with TMD was not supported by our findings. In the reverse direction, we did not find compelling evidence suggesting the causal effect of TMD on depression and anxiety disorder. CONCLUSIONS: The present study suggests a potential causal association between genetic liability for depression and the risk of TMD. Our MR findings align with prior epidemiological research, underscoring the significance of early detection and prevention of depression in the treatment of TMD.

Cascade Reactions Catalyzed by Gold Hybrid Nanoparticles Generate CO Gas Against Periodontitis in Diabetes.

The treatment of diabetic periodontitis poses a significant challenge due to the presence of local inflammation characterized by excessive glucose concentration, bacterial infection, and high oxidative stress. Herein, mesoporous silica nanoparticles (MSN) are embellished with gold nanoparticles (Au NPs) and loaded with manganese carbonyl to prepare a carbon monoxide (CO) enhanced multienzyme cooperative hybrid nanoplatform (MSN-Au@CO). The Glucose-like oxidase activity of Au NPs catalyzes the oxidation of glucose to hydrogen peroxide (H2O2) and gluconic acid，and then converts H2O2 to hydroxyl radicals (•OH) by peroxidase-like activity to destroy bacteria. Moreover, CO production in response to H2O2, together with Au NPs exhibited a synergistic anti-inflammatory effect in macrophages challenged by lipopolysaccharides. The underlying mechanism can be the induction of nuclear factor erythroid 2-related factor 2 to reduce reactive oxygen species, and inhibition of nuclear factor kappa-B signaling to diminish inflammatory response. Importantly, the antibacterial and anti-inflammation effects of MSN-Au@CO are validated in diabetic rats with ligature-induced periodontitis by showing decreased periodontal bone loss with good biocompatibility. To summarize, MSN-Au@CO is fabricate to utilize glucose-activated cascade reaction to eliminate bacteria, and synergize with gas therapy to regulate the immune microenvironment, offering a potential direction for the treatment of diabetic periodontitis.

Functionalized MoS2-nanosheets with NIR-Triggered nitric oxide delivery and photothermal activities for synergistic antibacterial and regeneration-promoting therapy.

Bacterial infection in skin and soft tissue has emerged as a critical concern. Overreliance on antibiotic therapy has led to numerous challenges, including the emergence of multidrug-resistant bacteria and adverse drug reactions. It is imperative to develop non-antibiotic treatment strategies that not only exhibit potent antibacterial properties but also promote rapid wound healing and demonstrate biocompatibility. Herein, a novel multimodal synergistic antibacterial system (SNO-CS@MoS2) was developed. This system employs easily surface-modified thin-layer MoS2 as photothermal agents and loaded with S-nitrosothiol-modified chitosan (SNO-CS) via electrostatic interactions, thus realizing the combination of NO gas therapy and photothermal therapy (PTT). Furthermore, this surface modification renders SNO-CS@MoS2 highly stable and capable of binding with bacteria. Through PTT's thermal energy, SNO-CS@MoS2 rapidly generates massive NO, collaborating with PTT to achieve antibacterial effects. This synergistic therapy can swiftly disrupt the bacterial membrane, causing protein leakage and ATP synthesis function damage, ultimately eliminating bacteria. Notably, after effectively eliminating all bacteria, the residual SNO-CS@MoS2 can create trace NO to promote fibroblast migration, proliferation, and vascular regeneration, thereby accelerating wound healing. This study concluded that SNO-CS@MoS2, a novel multifunctional nanomaterial with outstanding antibacterial characteristics and potential to promote wound healing, has promising applications in infected soft tissue wound treatment.

A Mendelian randomization study on the association of bone mineral density with periodontitis.

OBJECTIVE: Observational studies indicated that individuals with osteoporosis could be at an increased risk of periodontitis. This study aimed to investigate whether there is a causal association of bone mineral density (BMD) with periodontitis using Mendelian randomization (MR). MATERIALS AND METHODS: Summary statistics were sourced from genome-wide association study on BMD measured at different skeletal sites, including estimated heel BMD (eBMD, N = 426,824), forearm BMD (FA-BMD, N = 8143), femoral neck BMD (FN-BMD, N = 32,735), and lumbar spine BMD (LS-BMD, N = 28,498). Genetic variants of periodontitis (N = 45,563) and loose teeth (N = 461,031) were used as outcome surrogates. Inverse variance weighted meta-analysis (IVW) was adopted as main analyses. Other sensitivity MR approaches were used to boost power and account for pleiotropy. RESULTS: IVW results suggested no evidence for a causal association of any phenotypes of BMD with periodontitis (eBMD, odds ratio [OR] = 0.984, 95% confidence interval [CI] = 0.885-1.083; FA-BMD, OR = 1.028, 95%CI = 0.864-1.193; FN-BMD, OR = 1.033, 95%CI = 0.896-1.169; LS-BMD, OR = 0.991, 95%CI =0.878-1.103; all P > 0.65). Such null associations were consistent through other sensitivity MR approaches. Similarly, no significant causal effects of BMD on loose teeth were found. CONCLUSIONS: Within the limitation of the study, our MR estimates suggested that a decreased BMD is unlikely to substantially increase the risk of periodontitis.

Mendelian randomization supports the causal role of fasting glucose on periodontitis.

Purpose: The effect of hyperglycemia on periodontitis is mainly based on observational studies, and inconsistent results were found whether periodontal treatment favors glycemic control. The two-way relationship between periodontitis and hyperglycemia needs to be further elucidated. This study aims to evaluate the causal association of periodontitis with glycemic traits using bi-directional Mendelian randomization (MR) approach. Methods: Summary statistics were sourced from large-scale genome-wide association study conducted for fasting glucose (N = 133,010), HbA1c (N = 123,665), type 2 diabetes (T2D, N = 659,316), and periodontitis (N = 506,594) among European ancestry. The causal relationship was estimated using the inverse-variance weighted (IVW) model and further validated through extensive complementary and sensitivity analyses. Results: Overall, IVW showed that a genetically higher level of fasting glucose was significantly associated with periodontitis (OR = 1.119; 95% CI = 1.045-1.197; PFDR= 0.007) after removing the outlying instruments. Such association was robust and consistent through other MR models. Limited evidence was found suggesting the association of HbA1C with periodontitis after excluding the outliers (IVW OR = 1.123; 95% CI = 1.026-1.229; PFDR= 0.048). These linkages remained statistically significant in multivariate MR analyses, after adjusting for body mass index. The reverse direction MR analyses did not exhibit the causal association of genetic liability to periodontitis with any of the glycemic trait tested. Conclusions: Our MR study reaffirms previous findings and extends evidence to substantiate the causal effect of hyperglycemia on periodontitis. Future studies with robust genetic instruments are needed to confirm the causal association of periodontitis with glycemic traits.

Mendelian randomization highlights the causal association of obesity with periodontal diseases.

AIM: The underlying mechanisms connecting obesity and periodontal diseases remain unclear. This study investigates the potential causal association of obesity with periodontal diseases using Mendelian randomization (MR). MATERIALS AND METHODS: Single-nucleotide polymorphisms of obesity traits including body mass index (BMI), waist circumference (WC), and WC adjusted for BMI (WCadjBMI) from large-scale genome-wide association studies were screened for instrumental variables. The single trait periodontitis and the combined trait comprising periodontitis and loose teeth were adopted as surrogates for periodontal diseases. Inverse-variance weighted (IVW), series of sensitivity analyses and multivariable MR were employed to determine the association of obesity with periodontal diseases. RESULTS: IVW results showed that per 1-SD increment in BMI (odds ratio, OR = 1.115; 95% confidence interval [CI] = 1.064-1.169; p < .001) and WC (OR = 1.117; 95% CI = 1.052-1.185; p < .001), but not WCadjBMI, were significantly associated with an increased risk of periodontitis/loose teeth. Moreover, the MR estimates were consistent across other MR sensitivity analyses and multivariable MR. However, a causal association of obesity with the single trait periodontitis was not identified. CONCLUSIONS: The presented evidence supports previous epidemiological findings by showing a potential causal association of genetic liability to obesity with periodontal diseases. The biological mechanisms underlying this association warrant further investigation.