Li Lin

Background: To investigate whether the subgingival microbiota or the systemic immune‐inflammation index (SII) is more closely associated with the periodontal inflamed surface area (PISA). Methods: Ninety participants were enrolled in this cross‐sectional study for subgingival microbiota sequencing, SII, and PISA assessment. Restricted cubic spline and regression analyses examined the SII–PISA relationship. Microbiota analyses (LEfSe, alpha‐diversity, partitioning around medoids clustering) and interaction analyses were used to evaluate whether microbiota–SII interactions were associated with PISA. Results: A nonlinear relationship between PISA and SII was observed with a significant inflection point. In the High_SII group (log ₂ SII > 9.13), higher SII values were significantly associated with increased PISA ( P = 0.003). In the Low_SII group (log ₂ SII ≤ 9.13), increased PISA was linked to greater microbial richness ( P = 0.031) and a Porphyromonas ‐dominant microbial type. Stratified and interaction analyses provided additional support for these findings. Conclusion: At low SII levels, the periodontitis severity showed significant associations with microbial dysbiosis‐related features, whereas at higher SII levels, it was closely related to systemic immune cell imbalance, indicating that immune–inflammatory modulation may be particularly important for patients with a high SII level. Plain language summary: This study explored the links between a person's immune cell imbalance (assessed by the systemic immune‐inflammation index, SII), subgingival microbiota, and periodontitis severity. Ninety participants were tested for their blood cell markers of inflammation and the composition of microbiota. A nonlinear relationship between the SII and the periodontal inflamed surface area (PISA) was observed. There was a turning point: when SII was low, periodontitis severity was strongly linked to an imbalanced subgingival microbiota. However, when SII was high, periodontitis severity was more strongly related to an imbalance in immune cells. These findings indicate heterogeneity in the association among SII, oral microbiota, and periodontal inflammation.

This study investigated the relationship between periodontitis and metabolic dysfunction-associated steatotic liver disease (MASLD), with a specific focus

Purpose: Alveolar bone resorption in periodontitis is the primary clinical cause of tooth loss. This study aimed to investigate the inhibitory effect of Allium cepa L.-derived extracellular vesicles (AC-EVs) loaded with celecoxib (ACEV@CEL) on alveolar bone resorption. Methods: AC-EVs were isolated using gradient centrifugation in combination with ultracentrifugation, after which celecoxib was incorporated via ultrasonication to generate ACEV@CEL. Subsequently, a rat periodontitis model was established, and local administration was performed to systematically evaluate the biocompatibility and therapeutic effects on alveolar bone resorption. In vitro, after determining the optimal administration dose for each treatment group, we confirmed that RAW264.7 cells were able to internalize AC-EVs and ACEV@CEL. In the established in vitro periodontitis model, ACEV@CEL significantly inhibited osteoclast differentiation, and this inhibitory effect was stronger than that of either AC-EVs or celecoxib alone. Results: In vivo, ACEV@CEL exhibited good biocompatibility and effectively suppressed alveolar bone resorption in rats with periodontitis. In vitro, ACEV@CEL was internalized by RAW264.7 cells and inhibited their differentiation into osteoclasts. Conclusion: ACEV@CEL is able to suppress osteoclast differentiation under periodontitis conditions, while demonstrating favorable biocompatibility and safety, suggesting its potential as a therapeutic agent for periodontitis and warranting further long-term investigation. The process begins with onions, leading to AC-EVs, followed by density gradient centrifugation, ultracentrifugation and ultrasound, resulting in ACEV@CEL. Celecoxib is added during ultracentrifugation. In vivo testing involves a periodontitis model in rats, assessing biocompatibility and alveolar bone resorption inhibitory ability. In vitro testing uses RAW264.7 cells to evaluate AC-EVs and ACEV@CEL’s ability to inhibit osteoclast differentiation. Result analysis compares Celecoxib or AC-EVs with [email protected] abstract showing the preparation of ACEV@CEL and their therapeutic effects in periodontitis. ACEV@CEL is generated via ultrasonication and applied in a rat periodontitis model and RAW264.7 cells, demonstrating good biocompatibility, reduced alveolar bone resorption, and inhibition of osteoclast differentiation.

Background: The glycocalyx serves as the skeletal structure of the outer layer of endothelial cells and regulates the function of endothelial cells. Porphyromonas gingivalis ( P. gingivalis ) outer membrane vesicles (OMVs) exhibit the fundamental biological traits of bacteria, such as inducing inflammatory responses, damaging host cells, and delivering virulence factors to distal tissues like the cardiovascular system. This study aimed to investigate the role of P. gingivalis OMVs in vascular endothelial glycocalyx injury. Methods: In this clinical study, serum levels of syndecan-1 (SDC1) and heparan sulfate (HS), biomarkers of endothelial glycocalyx injury, were measured and compared between patients with stage III-IV periodontitis and those with stage I-II or no periodontitis. Then, glycocalyx injury was detected using transmission electron microscopy, immunofluorescence and western blotting after vascular endothelial cells were stimulated and C57BL/6J mice were administered with P. gingivalis OMVs via tail vein injection. Transcriptomic high-throughput sequencing analysis and in vitro and in vivo rescue experiments were conducted to determine the key mechanism in glycocalyx injury. Experiments were conducted using OMVs, ^PPAD−OE OMVs, and ^ΔPPAD OMVs to identify the special virulence factors in OMVs. Results: This study revealed that serum levels of SDC1 and HS were significantly higher in patients with stage III-IV periodontitis ( P < 0.05). A marked reduction in both the fluorescence intensity of the glycocalyx and the expression levels of its key components was observed in the OMVs group compared with control group ( P < 0.05). We identified the key differentially expressed gene B3GAT1 using high-throughput sequencing. Subsequent rescue experiments both in vitro and in vivo demonstrated that overexpression of B3GAT1 effectively restored glycocalyx integrity following injury ( P < 0.05). Notably, Porphyromonas gingivalis peptidylarginine deiminase (PPAD) was found to promote endovascular glycocalyx injury by citrullinating histone H3, thereby decreasing the expression of B3GAT1 ( P < 0.05). Conclusions: Our experiments demonstrated that biomarkers of endothelial glycocalyx injury were significantly higher in patients with stage III-IV periodontitis and PPAD could enter the cell nucleus, playing a vital role in vascular endothelial glycocalyx injury through the CitH3/B3GAT1 pathway. Graphical

Mitochondria are central to cellular energy metabolism and play a key role in regulating important physiological processes, including apoptosis and oxidative stress. Mitochondrial quality control has recently garnered significant attention, with the underlying mechanisms traditionally considered to be mitophagy and its dynamics. Various studies have demonstrated that extracellular vesicles are crucial for the transmission of mitochondria and their components. These vesicles effectively transport mitochondria to target cells, facilitating intercellular material exchange and signal transmission, thereby enhancing cellular function and viability. This review explores the mechanisms of mitochondrial transfer through mitochondrial extracellular vesicles (MitoEVs), analyzes the novel roles of MitoEVs in mitochondrial quality control, and discusses their applications in disease treatment. We aim to provide new perspectives for future research and support the development of relevant therapeutic strategies.

Periodontitis, a chronic inflammatory disease, is characterized by irreversible bone resorption, persistent attachment loss, and even ultimate tooth loss. The individual quality of life and the public burden of health are greatly impacted by the destruction of periodontal tissue and the lack of effective treatment. Exploration into how the inflammatory and damaged structure changes into the healthy and regenerative tissue is one of the most fascinating subjects in this field. A novel approach is the application of a nanoparticle, extracellular vesicle, which originates from natural or engineered cells. To further exploit its full potential, scientists have conducted massive studies into its biological and functional mechanisms. This review provides an overview of current extracellular vesicle-based treatments on periodontal diseases. It begins with summarizing the history of periodontal regeneration. Then, this article takes a general overview of extracellular vesicle’s biological characteristics, structures and current achievements. After that, we discussed extracellular vesicle’s functions in periodontium. In addition, this study also embraces a diverse range of extracellular vesicle-based strategies, a general workflow for EVs’ periodontal application. Finally, the challenges and prospects of the extracellular-based therapy have been discussed.

Aim: Porphyromonas gingivalis , a consensus periodontal pathogen, is thought to be involved in Alzheimer's disease (AD) progression, and P. gingivalis ‐derived outer membrane vesicles (PgOMVs) are a key toxic factor in inducing AD pathology. This study aimed to clarify the regulatory mechanism underlying the PgOMV‐induced AD‐like phenotype.Materials and Methods: We intraperitoneally injected PgOMVs into the periphery of wild‐type and CatB knockout mice for 4 or 8 weeks to assess the effect of CatB on PgOMV‐induced AD pathology. Mice were evaluated for cognitive change, tau phosphorylation, microglial activation, neuroinflammation and synapse loss. Microglial and primary neuron culture were prepared to verify the in vivo results.Results: CatB deficiency significantly alleviated PgOMV‐induced cognitive dysfunction, microglia‐mediated neuroinflammation, tau hyperphosphorylation and synapse loss. Subsequent transcriptomic analysis, immunofluorescence and immunoblotting suggested that CatB modulates microglia‐mediated neuroinflammation through stress‐activated protein kinases (SAPK)/Jun amino‐terminal kinases (JNK) signals after administration of PgOMVs, which in turn regulates neuronal tau phosphorylation and synapse loss in a SAPK/JNK‐dependent manner.Conclusion: Our study unveils a previously unknown role of CatB in regulating PgOMV‐induced AD pathology.

The approval of anti-amyloid β (Aβ) monoclonal antibodies (lecanemab) for the treatment of patients with early preclinical stage of Alzheimer’s disease (AD) by the Food and Drug Administration, suggests the reliability and importance of brain Aβ clearance for AD therapy. Microglia are the main phagocytes that clear Aβ in the brain, but the underlying regulatory mechanism is unclear. Here, we investigate the critical role of cathepsin B (CatB) in modulating microglial Aβ clearance from mouse brain. Wild-type or CatB^−/− mice were injected with Aβ into the hippocampus from 1 to 3 weeks. Mice were evaluated for cognitive change, Aβ metabolism, neuroinflammation. Microglia and neuron cultures were prepared to verify the in vivo results. The statistical analyses were performed by student’s t test, one-way ANOVA with a post hoc Tukey’s test using the GraphPad Prism software package. CatB deficiency significantly reduces Aβ clearance efficiency and aggravates mouse cognitive decline. Exogenous Aβ markedly increases CatB expression in activated microglia. Transcriptome analysis and in vitro cell culture experiments demonstrate that CatB is associated with gene clusters involved in migration, phagocytosis, and inflammation. In addition, transcriptome analysis and immunoblotting suggest that CatB modulates microglial Aβ clearance via PI3K-AKT activation. Our study unveils a previously unknown role of CatB in promoting microglial functionality during Aβ clearance.

To detect the association between periodontitis and all-cause as well as cause-specific mortality rates among adults diagnosed with depression. Participants diagnosed with depression were selected from NHANES across three periods (1988—1994; 1999—2004; 2009—2014). Cox proportional hazards and Weibull accelerated failure time (AFT) models were utilized to calculate hazard ratios (HRs), time ratios (TRs), and their 95% confidence intervals (CIs) to evaluate the association between moderate-to-severe periodontitis and all-cause as well as cause-specific mortality among participants with depression. white blood counts and C-reactive protein were used to assess the mediating role of systemic inflammation. Among the 1,189 participants with a median follow-up of 9.25 years, 133 deaths were recorded. After adjusting for multiple variables, moderate-to-severe periodontitis was obvious associated with an increased risk of cancer-related mortality in individuals with depression (Cox: HR 3.22, 95% CI 1.51—6.83, P = 0.002; AFT: TR 0.70, 95% CI 0.52—0.94, P = 0.017). Neither WBC nor CRP significantly mediate the association between periodontitis and cancer-related mortality. The risk of cancer-related mortality rose with the severity of periodontitis (P for trend = 0.021). However, no association was observed between moderate-to-severe periodontitis and other kinds of mortality. Moderate-to-severe periodontitis is linked to an elevated risk of cancer-related mortality among adults diagnosed with depression, with the mortality risk increasing alongside the severity of periodontitis. No significant mediating effect of systemic inflammation was found in this association. These findings highlight the importance of addressing periodontal health in individuals with depression. By uncovering the association between periodontitis and mortality in this population, our study underscores the potential benefits of preventive dental care and periodontal treatment in reducing the risk of cancer-related mortality in individuals with depression.

Background: Periodontitis is a chronic and multi-factorial infectious disease. A notable difference exists in the prognosis of patients with severe periodontitis after non-surgical periodontal treatment. Thus, a retrospective study was conducted to identify common and specific factors that impact the prognosis of patients with periodontitis stage III-IV following non-surgical periodontal treatment at different tooth sites. Methods: A total of 977 teeth were included in the study, comprising 266 patients diagnosed with periodontitis stage III-IV. This sample included 330 anterior teeth, 362 maxillary posterior teeth, and 285 mandibular posterior teeth. Following treatment, the teeth were categorized into two groups based on residual pocket depth [probing depth (PD) ≥ 5 mm] at 3 months post-treatment. The prognosis of periodontitis stage III-IV was assessed through multivariate analysis employing logistic regression to determine the association of various risk factors. Results: The PD values of each site and the deepest PD values of each tooth significantly decreased at 3 months post-treatment. Residual pockets were predominantly found in the mesio/disto-buccal and mesio/disto-lingual regions. Multivariate analysis revealed that gender, PD, sulcus bleeding index (SBI) and plaque index (PLI) at baseline, and crown-root ratio in anterior teeth had a significant influence on periodontitis stage III-IV (P < 0.05). Smoking, PD, PLI and furcation involvement (FI) at baseline, PLI at 3 months post-treatment, grades of periodontitis, and crown-root ratio were prediction factors for maxillary posterior teeth. Factors such as PD, PLI and FI at baseline, PLI at 3 months post-treatment, and crown-root were significant in mandibular posterior teeth. Conclusions: The outcome of non-surgical treatment varies depending on the tooth positions for patients with periodontitis stage III-IV. Dentists must accurately identify the affected teeth that have periodontal pockets of more than 5 mm, taking into consideration the positions of the affected teeth, as well as various local and systemic factors. This comprehensive assessment will enable dentists to develop a customized and effective treatment plan.