Gingipain from Porphyromonas gingivalis causes insulin resistance by degrading insulin receptors through direct proteolytic effects.

Periodontitis is a critical risk factor for the occurrence and development of diabetes. Porphyromonas gingivalis may participate in insulin resistance (IR) caused by periodontal inflammation, but the functional role and specific mechanisms of P. gingivalis in IR remain unclear. In the present study, clinical samples were analysed to determine the statistical correlation between P. gingivalis and IR occurrence. Through culturing of hepatocytes, myocytes, and adipocytes, and feeding mice P. gingivalis orally, the functional correlation between P. gingivalis and IR occurrence was further studied both in vitro and in vivo. Clinical data suggested that the amount of P. gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score. In vitro studies suggested that coculture with P. gingivalis decreased glucose uptake and insulin receptor (INSR) protein expression in hepatocytes, myocytes, and adipocytes. Mice fed P. gingivalis tended to undergo IR. P. gingivalis was detectable in the liver, skeletal muscle, and adipose tissue of experimental mice. The distribution sites of gingipain coincided with the downregulation of INSR. Gingipain proteolysed the functional insulin-binding region of INSR. Coculture with P. gingivalis significantly decreased the INSR-insulin binding ability. Knocking out gingipain from P. gingivalis alleviated the negative effects of P. gingivalis on IR in vivo. Taken together, these findings indicate that distantly migrated P. gingivalis may directly proteolytically degrade INSR through gingipain, thereby leading to IR. The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.

Pyroptotic macrophages induce disruption of glutamate metabolism in periodontal ligament stem cells contributing to their compromised osteogenic potential.

Macrophage pyroptosis is of key importance to host defence against pathogen infections and may participate in the progression and recovery of periodontitis. However, the role of pyroptotic macrophages in regulating periodontal ligament stem cells (PDLSCs), the main cell source for periodontium renewal, remains unclear. First, we found that macrophage pyroptosis were enriched in gingiva tissues from periodontitis patients compared with those of healthy people through immunofluorescence. Then the effects of pyroptotic macrophages on the PDLSC osteogenic differentiation were investigated in a conditioned medium (CM)-based coculture system in vitro. CM derived from pyroptotic macrophages inhibited the osteogenic differentiation-related gene and protein levels, ALP activity and mineralized nodule formation of PDLSCs. The osteogenic inhibition of CM was alleviated when pyroptosis was inhibited by VX765. Further, untargeted metabolomics showed that glutamate limitation may be the underlying mechanism. However, exogenous glutamate supplementation aggravated the CM-inhibited osteogenic differentiation of PDLSCs. Moreover, CM increased extracellular glutamate and decreased intracellular glutamate levels of PDLSCs, and enhanced the gene and protein expression levels of system xc - (a cystine/glutamate antiporter). After adding cystine to CM-based incubation, the compromised osteogenic potency of PDLSCs was rescued. Our data suggest that macrophage pyroptosis is related to the inflammatory lesions of periodontitis. Either pharmacological inhibition of macrophage pyroptosis or nutritional supplements to PDLSCs, can rescue the compromised osteogenic potency caused by pyroptotic macrophages.

Harnessing Mechanical Stress with Viscoelastic Biomaterials for Periodontal Ligament Regeneration.

The viscoelasticity of mechanically sensitive tissues such as periodontal ligaments (PDLs) is key in maintaining mechanical homeostasis. Unfortunately, PDLs easily lose viscoelasticity (e.g., stress relaxation) during periodontitis or dental trauma, which disrupt cell-extracellular matrix (ECM) interactions and accelerates tissue damage. Here, Pluronic F127 diacrylate (F127DA) hydrogels with PDL-matched stress relaxation rates and high elastic moduli are developed. The hydrogel viscoelasticity is modulated without chemical cross-linking by controlling precursor concentrations. Under cytomechanical loading, F127DA hydrogels with fast relaxation rates significantly improved the fibrogenic differentiation potential of PDL stem cells (PDLSCs), while cells cultured on F127DA hydrogels with various stress relaxation rates exhibited similar fibrogenic differentiation potentials with limited cell spreading and traction forces under static conditions. Mechanically, faster-relaxing F127DA hydrogels leveraged cytomechanical loading to activate PDLSC mechanotransduction by upregulating integrin-focal adhesion kinase pathway and thus cytoskeletal rearrangement, reinforcing cell-ECM interactions. In vivo experiments confirm that faster-relaxing F127DA hydrogels significantly promoted PDL repair and reduced abnormal healing (e.g., root resorption and ankyloses) in delayed replantation of avulsed teeth. This study firstly investigated how matrix nonlinear viscoelasticity influences the fibrogenesis of PDLSCs under mechanical stimuli, and it reveals the underlying mechanobiology, which suggests novel strategies for PDL regeneration.

Expert consensus on odontogenic maxillary sinusitis multi-disciplinary treatment.

ABSTARCT: Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multi-disciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.

Journey of Mineral Precursors in Bone Mineralization: Evolution and Inspiration for Biomimetic Design.

Bone mineralization is a ubiquitous process among vertebrates that involves a dynamic physical/chemical interplay between the organic and inorganic components of bone tissues. It is now well documented that carbonated apatite, an inorganic component of bone, is proceeded through transient amorphous mineral precursors that transforms into the crystalline mineral phase. Here, the evolution on mineral precursors from their sources to the terminus in the bone mineralization process is reviewed. How organisms tightly control each step of mineralization to drive the formation, stabilization, and phase transformation of amorphous mineral precursors in the right place, at the right time, and rate are highlighted. The paradigm shifts in biomineralization and biomaterial design strategies are intertwined, which promotes breakthroughs in biomineralization-inspired material. The design principles and implementation methods of mineral precursor-based biomaterials in bone graft materials such as implant coatings, bone cements, hydrogels, and nanoparticles are detailed in the present manuscript. The biologically controlled mineralization mechanisms will hold promise for overcoming the barriers to the application of biomineralization-inspired biomaterials.

Third molar-related knowledge, attitudes, behaviors, and medical history of 904 Chinese adults: a cross-sectional survey. / 904åä¸­å›½æˆå¹´äººå¯¹ç¬¬ä¸‰ç£¨ç‰™ç›¸å ³çŸ¥è¯†ã€æ€åº¦ã€è¡Œä¸ºå’Œç— å²çš„æ¨ªæ–­é¢ç ”ç©¶.

This study investigated the perceptions and medical history of third molars (M3s) and assessed the prevalence of visible M3s (V-M3s) among 904 Chinese adults. The enrolled participants were interviewed to complete a structural questionnaire focused on sociodemographic information and their understanding of, attitudes toward, behaviors regarding, and medical history with respect to M3s. In addition, the number of V-M3s in the cohort was determined by oral examination. Logistic regression analysis was performed to explore the association between individuals' sociodemographic characteristics and their perception of M3s or the presence of V-M3s. The Chi-square test was used to compare the actions taken against symptomatic M3s and the corresponding outcomes among different groups divided according to respondents' sociodemographic factors. In total, 904 completed questionnaires were gathered and analyzed. Nearly half (43.9%) of the respondents knew nothing about M3s, and only 12.7% provided correct answers to all the questions asked. Male sex, older age, occupation involving physical labor, and no previous dental experience were active factors in unawareness of M3s. Male sex was also significantly associated with the presence of at least one V-M3 and negative behavior about symptomatic M3s. In terms of medical history, 192 participants reported having had at least one M3 extracted (438 in total), and 72.6% of the M3s were removed due to the presence of related symptoms or pathologies. In conclusion, the population investigated had a shortage of knowledge about M3s and adopted negative attitudes and actions about M3-related problems.

ßIV-Spectrin in Cardiac Fibroblasts: Implications for Fibrosis and Therapeutic Targeting in Cardiac Diseases. Comment on Nassal et al. Spectrin-Based Regulation of Cardiac Fibroblast Cell-Cell Communication. Cells 2023, 12, 748.

Fibroblasts in the heart, traditionally recognized as interstitial cells, have long been overlooked in the study of cardiac physiology and pathology [...].

Non-Impacted Third Molars: Angels or Devils?

Third molars, also known as wisdom teeth, are located in the most posterior of the tooth arch [...].

NADPH-dependent ROS accumulation contributes to the impaired osteogenic differentiation of periodontal ligament stem cells under high glucose conditions.

Diabetes mellitus is an established risk factor for periodontal disease that can aggravate the severity of periodontal inflammation and accelerate periodontal destruction. The chronic high glucose condition is a hallmark of diabetes-related pathogenesis, and has been demonstrated to impair the osteogenic differentiation of periodontal ligament stem cells (PDLSCs), leading to delayed recovery of periodontal defects in diabetic patients. Reactive oxygen species (ROS) are small molecules that can influence cell fate determination and the direction of cell differentiation. Although excessive accumulation of ROS has been found to be associated with high glucose-induced cell damage, the underlying mechanisms remain unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) is an important electron donor and functions as a critical ROS scavenger in antioxidant systems. It has been identified as a key mediator of various biological processes, including energy metabolism and cell differentiation. However, whether NADPH is involved in the dysregulation of ROS and further compromise of PDLSC osteogenic differentiation under high glucose conditions is still not known. In the present study, we found that PDLSCs incubated under high glucose conditions showed impaired osteogenic differentiation, excessive ROS accumulation and increased NADPH production. Furthermore, after inhibiting the synthesis of NADPH, the osteogenic differentiation of PDLSCs was significantly enhanced, accompanied by reduced cellular ROS accumulation. Our findings demonstrated the crucial role of NADPH in regulating cellular osteogenic differentiation under high glucose conditions and suggested a new target for rescuing high glucose-induced cell dysfunction and promoting tissue regeneration in the future.

Autophagy, a double-edged sword for oral tissue regeneration.

BACKGROUND: Oral health is of fundamental importance to maintain systemic health in humans. Stem cell-based oral tissue regeneration is a promising strategy to achieve the recovery of impaired oral tissue. As a highly conserved process of lysosomal degradation, autophagy induction regulates stem cell function physiologically and pathologically. Autophagy activation can serve as a cytoprotective mechanism in stressful environments, while insufficient or over-activation may also lead to cell function dysregulation and cell death. AIM OF REVIEW: This review focuses on the effects of autophagy on stem cell function and oral tissue regeneration, with particular emphasis on diverse roles of autophagy in different oral tissues, including periodontal tissue, bone tissue, dentin pulp tissue, oral mucosa, salivary gland, maxillofacial muscle, temporomandibular joint, etc. Additionally, this review introduces the molecular mechanisms involved in autophagy during the regeneration of different parts of oral tissue, and how autophagy can be regulated by small molecule drugs, biomaterials, exosomes/RNAs or other specific treatments. Finally, this review discusses new perspectives for autophagy manipulation and oral tissue regeneration. KEY SCIENTIFIC CONCEPTS OF REVIEW: Overall, this review emphasizes the contribution of autophagy to oral tissue regeneration and highlights the possible approaches for regulating autophagy to promote the regeneration of human oral tissue.

Biotin-Avidin System-Based Delivery Enhances the Therapeutic Performance of MSC-Derived Exosomes.

Exosomes (EXs) shed by mesenchymal stem cells (MSCs) are potent therapeutic agents that promote wound healing and regeneration, but when used alone in vivo, their therapeutic potency is diminished by rapid clearance and bioactivity loss. Inspired by the biotin-avidin interaction, we developed a simple yet versatile method for the immobilization of MSC-derived EXs (MSC-EXs) into hydrogels and achieved sustained release for regenerative purposes. First, biotin-modified gelatin methacryloyl (Bio-GelMA) was fabricated by grafting NHS-PEG12-biotin onto the amino groups of GelMA. Biotin-modified MSC-EXs (Bio-EXs) were then synthesized using an in situ self-assembling biotinylation strategy, which provided sufficient binding sites for MSC-EX delivery with little effect on their cargo composition. Thereafter, Bio-EXs were immobilized in Bio-GelMA via streptavidin to generate Bio-GelMA@Bio-EX hydrogels. An in vitro analysis demonstrated that Bio-EXs could be taken up by macrophages and exerted immunomodulatory effects similar to those of MSC-EXs, and Bio-GelMA@Bio-EX hydrogels provided sustained release of MSC-EXs for 7 days. After subcutaneous transplantation, a more constant retention of MSC-EXs in Bio-GelMA@Bio-EX hydrogels was observed for up to 28 days. When placed in an artificial periodontal multitissue defect, the functionalized hydrogels exhibited an optimized therapeutic performance to regrow complex periodontal tissues, including acellular cementum, periodontal ligaments (PDLs), and alveolar bone. In this context, Bio-GelMA@Bio-EX hydrogels exerted a robust immunomodulatory effect that promoted macrophage polarization toward an M2 phenotype. Our findings demonstrate that MSC-EXs delivered with the aid of the biotin-avidin system exhibit robust macrophage-modulating and repair-promoting functions and suggest a universal approach for the development of MSC-EX-functionalized biomaterials for advanced therapies.

Periodontitis exacerbates atherosclerosis through Fusobacterium nucleatum-promoted hepatic glycolysis and lipogenesis.

AIMS: Positive associations between periodontitis (PD) and atherosclerosis have been established, but the causality and mechanisms are not clear. We aimed to explore the causal roles of PD in atherosclerosis and dissect the underlying mechanisms. METHODS AND RESULTS: A mouse model of PD was established by ligation of molars in combination with application of subgingival plaques collected from PD patients and then combined with atherosclerosis model induced by treating atheroprone mice with a high-cholesterol diet (HCD). PD significantly aggravated atherosclerosis in HCD-fed atheroprone mice, including increased en face plaque areas in whole aortas and lesion size at aortic roots. PD also increased circulating levels of triglycerides and cholesterol, hepatic levels of cholesterol, and hepatic expression of rate-limiting enzymes for lipogenesis. Using 16S ribosomal RNA (rRNA) gene sequencing, Fusobacterium nucleatum was identified as the most enriched PD-associated pathobiont that is present in both the oral cavity and livers. Co-culture experiments demonstrated that F. nucleatum directly stimulated lipid biosynthesis in primary mouse hepatocytes. Moreover, oral inoculation of F. nucleatum markedly elevated plasma levels of triglycerides and cholesterol and promoted atherogenesis in HCD-fed ApoE-/- mice. Results of RNA-seq and Seahorse assay indicated that F. nucleatum activated glycolysis, inhibition of which by 2-deoxyglucose in turn suppressed F. nucleatum-induced lipogenesis in hepatocytes. Finally, interrogation of the molecular mechanisms revealed that F. nucleatum-induced glycolysis and lipogenesis by activating PI3K/Akt/mTOR signalling pathway in hepatocytes. CONCLUSIONS: PD exacerbates atherosclerosis and impairs lipid metabolism in mice, which may be mediated by F. nucleatum-promoted glycolysis and lipogenesis through PI3K/Akt/mTOR signalling in hepatocytes. Treatment of PD and specific targeting of F. nucleatum are promising strategies to improve therapeutic effectiveness of hyperlipidaemia and atherosclerosis.

Periodontitis salivary microbiota exacerbates nonalcoholic fatty liver disease in high-fat diet-induced obese mice.

Periodontitis may aggravate the development of nonalcoholic fatty liver disease (NAFLD); however, the precise mechanism is unknown. In this study, salivary microbiota collected from patients with periodontitis was transferred intragastrically to obese mice induced by high-fat diet. Microbiomics and metabolomics analysis were performed to assess the influence of periodontitis salivary microbiota on gut microbiome and liver metabolism. Periodontitis salivary microbiota altered gut microbiota composition and exacerbated intestinal barrier dysfunction in obese mice. Subsequently, the bacterial lipopolysaccharide transported to liver may activate the toll-like receptor 4 signaling and cause the release of pro-inflammatory factors. Moreover, the tryptophan-kynurenine-AhR signal axis was upregulated in liver, which may be related to aggravated hepatic steatosis and glucolipid metabolism dysregulation during NAFLD development. This study indicated that in the context of obesity, periodontitis salivary microbiota may aggravate the pathological progression of NAFLD, in which the tryptophan-AhR pathway may play a key role.

Long non-coding RNA AC018926.2 regulates palmitic acid exposure-compromised osteogenic potential of periodontal ligament stem cells via the ITGA2/FAK/AKT pathway.

Although obesity has been proposed as a risk factor for periodontitis, the influence of excessive fat accumulation on the development of periodontitis and periodontal recovery from disease remains largely unknown. This study investigated the cellular response of periodontal ligament stem cells (PDLSCs) to elevated levels of a specific fatty acid, namely, palmitic acid (PA). The mechanism by which PA exposure compromises the osteogenic potential of cells was also explored. It was found that exposure of PDLSCs to abundant PA led to decreased cell osteogenic differentiation. Given that long non-coding RNAs (lncRNAs) play a key role in the stem cell response to adverse environmental stimuli, we screened the lncRNAs that were differentially expressed in PDLSCs following PA exposure using lncRNA microarray analysis, and AC018926.2 was identified as the lncRNA that was most sensitive to PA. Next, gain/loss-of-function studies illustrated that AC018926.2 was an important regulator in PA-mediated osteogenic differentiation of PDLSCs. Mechanistically, AC018926.2 upregulated integrin α2 (ITGA2) expression and therefore activated ITGA2/FAK/AKT signalling. Further functional studies revealed that inactivation of ITGA2/FAK/AKT signalling by silencing ITGA2 counteracted the pro-osteogenic effect induced by AC018926.2 overexpression. Moreover, the results of bioinformatics analysis and RNA immunoprecipitation assay suggested that AC018926.2 might transcriptionally regulate ITGA2 expression by binding to PARP1 protein. Our data suggest that AC018926.2 may serve as a therapeutic target for the management of periodontitis in obese patients.

Enhanced removal of Pb from electrolytic manganese anode slime and preparation of chemical MnO2.

Electrolytic manganese anode slime (EMAS) is produced during the production of electrolytic manganese metal. In this study, a method based on vacuum carbothermal reduction was used for Pb removal in EMAS. A Pb-removal efficiency of 99.85% and MnO purity in EMAS of 97.34 wt.% were obtained for a reduction temperature of 950°C and a carbon mass ratio of 10% for a holding time of 100 min. The dense structure of the EMAS was destroyed, a large number of multidimensional pores and cracks were formed, and the Pb-containing compound was reduced to elemental Pb by the vacuum carbothermal reduction. A recovery efficiency for chemical MnO2 of 36.6% was obtained via preparation from Pb-removed EMAS through the 'roasting-pickling disproportionation' process, with an acid washing time of 100 min, acid washing temperature of 70°C, H2SO4 concentration of 0.8 mol·L-1, liquid-solid mass ratio of 7 mL·g-1, calcination temperature of 60°C and calcination time of 2.5 h. Moreover, the crystal form of the prepared chemical MnO2 was found to be basically the same as that of electrolytic MnO2, and its specific surface area, micropore volume and discharge capacity were all higher than that of electrolytic MnO2. This study provides a new method for Pb removal and recycling for EMAS.HighlightsVacuum carbothermal reduction method was used for Pb removal in EMAS.The removal efficiency of Pb was 99.85%.Chemical MnO2 with excellent discharge performance was prepared using treated EMAS.This study provides a new method for EMAS resource utilization.

The impact of Anatomic Features of Asymptomatic Third Molars on the Pathologies of Adjacent Second Molars: A Cross-sectional Analysis.

BACKGROUND: We aimed to comprehensively examine how the anatomic characteristics of asymptomatic third molars (As-M3s) affect distal pathologies of adjacent second molars (Ad-M2s). MATERIALS AND METHODS: Patients with at least 1 quadrant having intact As-M3s and first and second molars were enrolled. Distal pathologies of Ad-M2s, including caries, pocket depth of 4 mm or more (PD4+), and alveolar bone loss of 3 mm or more (ABL3+), were analysed based on As-M3 status (absent/impacted/nonimpacted). Especially within nonimpacted M3s (N-M3s), the effects of regions (maxillary vs mandibular) and dental intervals (narrow vs wide) on Ad-M2 pathologies were further compared. RESULTS: A total of 248 patients with their 805 quadrants were finally included in this cross-sectional study. The impacted and nonimpacted As-M3s elevated the risk of any distal pathology (caries, PD4+, or ABL3+) of Ad-M2s vs M3 absence with odds ratios (ORs) of 8.33 and 3.27, respectively. Within N-M3s, mandibular regions increased the odds of PD4+ (OR, 1.96); wide dental intervals increased the odds of ABL3+ (OR, 3.01). However, maxillary regions and narrow dental intervals contributed to more severe bone loss in Ad-M2s with ABL3+. CONCLUSIONS: The presence of As-M3 is a risk factor for Ad-M2 pathologies irrespective of impaction status. Within N-M3s, Ad-M2 pathologies are significantly influenced by anatomic characteristics such as regions and dental intervals.

Evolution of gene regulatory network of C4 photosynthesis in the genus Flaveria reveals the evolutionary status of C3-C4 intermediate species.

C4 photosynthesis evolved from ancestral C3 photosynthesis by recruiting pre-existing genes to fulfill new functions. The enzymes and transporters required for the C4 metabolic pathway have been intensively studied and well documented; however, the transcription factors (TFs) that regulate these C4 metabolic genes are not yet well understood. In particular, how the TF regulatory network of C4 metabolic genes was rewired during the evolutionary process is unclear. Here, we constructed gene regulatory networks (GRNs) for four closely evolutionarily related species from the genus Flaveria, which represent four different evolutionary stages of C4 photosynthesis: C3 (F. robusta), type I C3-C4 (F. sonorensis), type II C3-C4 (F. ramosissima), and C4 (F. trinervia). Our results show that more than half of the co-regulatory relationships between TFs and core C4 metabolic genes are species specific. The counterparts of the C4 genes in C3 species were already co-regulated with photosynthesis-related genes, whereas the required TFs for C4 photosynthesis were recruited later. The TFs involved in C4 photosynthesis were widely recruited in the type I C3-C4 species; nevertheless, type II C3-C4 species showed a divergent GRN from C4 species. In line with these findings, a 13CO2 pulse-labeling experiment showed that the CO2 initially fixed into C4 acid was not directly released to the Calvin-Benson-Bassham cycle in the type II C3-C4 species. Therefore, our study uncovered dynamic changes in C4 genes and TF co-regulation during the evolutionary process; furthermore, we showed that the metabolic pathway of the type II C3-C4 species F. ramosissima represents an alternative evolutionary solution to the ammonia imbalance in C3-C4 intermediate species.

Roles of extracellular vesicles in periodontal homeostasis and their therapeutic potential.

Periodontal tissue is a highly dynamic and frequently stimulated area where homeostasis is easily destroyed, leading to proinflammatory periodontal diseases. Bacteria-bacteria and cell-bacteria interactions play pivotal roles in periodontal homeostasis and disease progression. Several reviews have comprehensively summarized the roles of bacteria and stem cells in periodontal homeostasis. However, they did not describe the roles of extracellular vesicles (EVs) from bacteria and cells. As communication mediators evolutionarily conserved from bacteria to eukaryotic cells, EVs secreted by bacteria or cells can mediate interactions between bacteria and their hosts, thereby offering great promise for the maintenance of periodontal homeostasis. This review offers an overview of EV biogenesis, the effects of EVs on periodontal homeostasis, and recent advances in EV-based periodontal regenerative strategies. Specifically, we document the pathogenic roles of bacteria-derived EVs (BEVs) in periodontal dyshomeostasis, focusing on plaque biofilm formation, immune evasion, inflammatory pathway activation and tissue destruction. Moreover, we summarize recent advancements in cell-derived EVs (CEVs) in periodontal homeostasis, emphasizing the multifunctional biological effects of CEVs on periodontal tissue regeneration. Finally, we discuss future challenges and practical perspectives for the clinical translation of EV-based therapies for periodontitis.

How the Loss of Second Molars Corresponds with the Presence of Adjacent Third Molars in Chinese Adults: A Retrospective Study.

Third molars (M3s) can increase the pathological risks of neighboring second molars (M2s). However, whether the M3 presence affects M2 loss remains unknown. This retrospective study aimed to reveal the reasons for M2 loss and how M2 loss relates to neighboring M3s. The medical records and radiographic images of patients with removed M2(s) were reviewed to analyze why the teeth were extracted and if those reasons were related to adjacent M3s. Ultimately, 800 patients with 908 removed M2s were included. In the included quadrants, 526 quadrants with M3s were termed the M3 (+) group, and the other 382 quadrants without M3s were termed the M3 (−) group. The average age of patients in the M3 (+) group was 52.4 ± 14.8 years and that of the M3 (−) group was 56.7 ± 14.9 years, and the difference between the two groups was statistically significant (p < 0.001). Of the 908 M2s, 433 (47.7%) were removed due to caries and sequelae and 300 (33.0%) were removed due to periodontal diseases. Meanwhile, 14.4% of the M2s with adjacent M3s were removed due to distal caries and periodontitis, which were closely related to the neighboring M3s; this percentage was much lower when M3 were absent (1.8%). Additionally, 42.2% of M3s were removed simultaneously with neighboring M2s. The presence of M3s, regardless of impaction status, was associated with an earlier loss of their neighboring M2s.