BACKGROUND: Regenerative endodontic procedures (REPs) is effective for treating young permanent teeth with pulp necrosis. However, its efficacy on delayed replanted avulsed teeth is unclear.
OBJECTIVE: This retrospective study aimed to assess the efficacy of REPs in treating delayed replanted immature permanent teeth with apical periodontitis.
METHODS: Avulsed teeth receiving REPs were systematically screened based on predetermined criteria. This study assessed the REP outcomes, postoperative periodontal healing, and overall treatment efficacy. Samples were grouped by REP outcomes and root development stage, with Fisher\'s exact tests used to compare outcomes among different groups.
RESULTS: Among the included 17 teeth, 47.1% exhibited successful REPs and periodontal healing. Another 47.1%, due to replacement resorption or REP failure, were categorized as tooth survival. Healing of periapical lesions was observed in 88.2% of the cases, but only 41.2% demonstrated continued root development. Although differences were not significant (p = 0.05), teeth with continued root development had a higher rate of functional healing (85.7%) compared to those without (30%).
CONCLUSIONS: Within the limitations of this study, REPs presented reliable outcomes for treating delayed replanted immature permanent teeth with apical periodontitis mainly in periapical lesion healing. Teeth with continued root development after REPs exhibited a higher rate of functional healing. Further investigation is required to explore potential synergies between REP outcomes and periodontal healing.

Tooth-related inflammatory disorders, including caries, pulpitis, apical periodontitis (AP), and periodontitis (PD), are primarily caused by resident oral microorganisms. Although these dental inflammatory conditions are typically not life-threatening, neglecting them can result in significant complications and greatly reduce an individual\'s quality of life. Nuclear factor κB (NF-κB), a family formed by various combinations of Rel proteins, is extensively involved in inflammatory diseases and even cancer. This study reviews recent data on NF-κB signaling and its role in dental pulp stem cells (DPSCs), dental pulp fibroblasts (DPFs), odontoblasts, human periodontal ligament cells (hPDLCs), and various experimental animal models. The findings indicate that NF-κB signaling is abnormally activated in caries, pulpitis, AP, and PD, leading to changes in related cellular differentiation. Under specific conditions, NF-κB signaling occasionally interacts with other signaling pathways, affecting inflammation, bone metabolism, and tissue regeneration processes. In summary, data collected over recent years confirm the central role of NF-κB in dental inflammatory diseases, potentially providing new insights for drug development targeting NF-κB signaling pathways in the treatment of these conditions. Keywords: NF-κB, dental caries, pulpitis, apical periodontitis, periodontitis.

UNASSIGNED: The primary cause of pulp and periapical diseases is the invasion of bacteria into the root canal, which results from the continuous destruction of dental hard tissues. Effective management of infections during root canal therapy necessitates effectively irrigation. This study aims to investigate the effects of two antimicrobial peptides (AMPs), buCaTHL4B and Im-4, on root canal biofilms in vitro.
UNASSIGNED: Two-species biofilms (Enterococcus faecalis and Fusobacterium nucleatum) were selected and anaerobically cultivated. The following treatments were applied: 10 μg/mL buCaTHL4B, 10 μg/mL Im-4, 5 μg/mL buCaTHL4B, 5 μg/mL Im-4, 1 μg/mL buCaTHL4B, 1 μg/mL Im-4, 1% NaOCl, and sterile water. Each group was treated for 3 min. Subsequently, the two strains were co-cultured with 10 μg/mL buCaTHL4B, 10 μg/mL Im-4, 1% NaOCl, and sterile water for 24, 48, and 72 h. The biofilms were examined using confocal laser scanning microscopy (CLSM) with fluorescent staining, and the percentages of dead bacteria were calculated. Quantitative real-time PCR (qRT-PCR) was employed to assess the variations in bacterial proportions during biofilm formation.
UNASSIGNED: Compared to 1% NaOCl, 10 μg/mL buCaTHL4B or Im-4 exhibited significantly greater bactericidal effects on the two-species biofilms (p < 0.05), leading to their selection for subsequent experiments. Over a 48-hour period, 10 μg/mL Im-4 demonstrated a stronger antibiofilm effect than buCaTHL4B (p < 0.05). Following a 24-hour biofilm formation period, the proportion of F. nucleatum decreased while the proportion of E. faecalis increased in the sterile water group. In the buCaTHL4B and 1% NaOCl groups, the proportion of F. nucleatum was lower than that of E. faecalis (p < 0.05), whereas in the Im-4 group, the proportion of F. nucleatum was higher than that of E. faecalis (p < 0.05). The proportions of bacteria in the two AMPs groups gradually stabilized after 24 h of treatment.
UNASSIGNED: buCaTHL4B and Im-4 exhibited remarkable antibacterial and anti-biofilm capabilities against pathogenic root canal biofilms in vitro, indicating their potential as promising additives to optimize the effectiveness of root canal treatment as alternative irrigants.

OBJECTIVE: The objectives of current study were to investigate the role and related mechanism of Ginsenoside Rb1 (GRb1) on regulating apical periodontitis (AP) prognosis.
METHODS: Clinical specimens were used to determine the involvement of calcium overload-induced macrophage pyroptosis in periapical tissues. Next, a calcium ion-chelating agent (BAPTA-AM) was applied to detect the suppression of intracellular calcium overload in macrophage pyroptosis. Then, network pharmacology, western blot (WB) analysis, and Fluo-4 calcium assay were conducted to explore the role of GRb1 on intracellular calcium overload. To gain a better understanding of GRb1 in calcium overload-induced macrophage pyroptosis linked AP, GRb1-treated AP models were established.
RESULTS: We discovered clinically and experimentally that calcium overload-dependent macrophage pyroptosis is involved in AP pathogenesis, and reducing calcium overload greatly decreased macrophage pyroptosis in an AP cell model. Next, based on GRb1\'s inhibitory role in aberrant intracellular calcium accumulation, we discovered that GRb1 alleviates AP by suppressing calcium-dependent macrophage pyroptosis in both in vitro and in vivo models.
CONCLUSIONS: GRb1 is an effective therapeutic strategy to rescue the periapical tissues from inflammation due to its anti-pyroptosis function. Thus, the present study supports further investigation of GRb1 as an adjuvant therapy for AP.

UNASSIGNED: Gremlin1 is a multifunctional protein whose expression is demonstrated to be involved in a series of physiology and pathological processes. The association between Gremlin1 and apcial periodontitis (AP) has been established. M1-polarized macrophages are crucial immune cells that exacerbate the progression of apical periodontal inflammatory response, but the function of Gremlin1 during macrophages activation in periapical lesions is still unclear. This study attempts to explore the regulatory effects of Gremlin1 on macrophage polarization on apical periodontitis microenviroment.
UNASSIGNED: Clinical specimens were used to determine the expression of Gremlin1 in periapical tissues by immunohistochemical (IHC) staining. Then, the disease models of periapical inflammation in rats were established, and adenovirus- associated virus (AAVs) was used to blockade Gremlin1 expression. Lentivirus carrying sh-Gremlin1 particles were used to transfect THP-1 induced M1-subtype macrophages. To assess the expression of associated molecules, Western blot, immunofluorescence staining were performed.
UNASSIGNED: Gremlin1 was significantly up-regulated in the periapical tissues of subjects with AP as identified by IHC staining, and positively correlated with levels of M1 macrophage-associated genes. Rats AP model with inhibition of Gremlin1 in periapical lesions exhibited limited infiltration of macrophages and decreased expression of M1 macrophage-related genes in periapical lesions. Furthermore, Gremlin1 blockade substantially decreased the Notch1/Hes1 signaling pathway activation level. The in vitro experiments confirmed the above results.
UNASSIGNED: Taken together, current study illustrated that the Gremlin1 suppression in periapical lesions inhibited M1 macrophage polarization through Notch1/Hes1 axis. Moreover, Gremlin1 may act as a potential candidate in the treatment of AP.

Apical periodontitis (AP) is featured by a persistent inflammatory response and alveolar bone resorption initiated by microorganisms, posing risks to both dental and systemic health. Nonsurgical endodontic treatment is the recommended treatment plan for AP with a high success rate, but in some cases, periapical lesions may persist despite standard endodontic treatment. Better comprehension of the AP inflammatory microenvironment can help develop adjunct therapies to improve the outcome of endodontic treatment. This review presents an overview of the immune landscape in AP, elucidating how microbial invasion triggers host immune activation and shapes the inflammatory microenvironment, ultimately impacting bone homeostasis. The destructive effect of excessive immune activation on periapical tissues is emphasized. This review aimed to systematically discuss the immunological basis of AP, the inflammatory bone resorption and the immune cell network in AP, thereby providing insights into potential immunotherapeutic strategies such as targeted therapy, antioxidant therapy, adoptive cell therapy and cytokine therapy to mitigate AP-associated tissue destruction.

Dental invagination is an abnormality of the crown or root development induced during tooth germ development when the enamel-forming apparatus or epithelial root sheath overpopulates and folds into the papilla. In severe cases, the invaginated channels are connected to the pulp and periodontal tissues, often causing endodontic and periapical diseases. The complex anatomical pattern of this disease adds difficulty in its preoperative diagnosis and clinical operation. In this paper, we report a case of non-surgical treatment assisted by cone beam CT and microscopy for maxillary lateral incisor double dens invaginatus type Ⅲ (Ⅲa and Ⅲb) with apical periapical infection. After 1-year follow-up, the affected tooth was asymptomatic and the periapical lesion was significantly reduced.
牙内陷是牙胚发育期成釉器或上皮根鞘过度增殖，卷叠入牙乳头引起的牙冠或牙根发育异常。严重内陷的患牙内陷通道与牙髓和牙周组织相通，常引起牙髓病和根尖周病，其复杂的解剖形态为术前诊断和临床操作增加了难度。本文报道了1例上颌侧切牙Ⅲ型双牙内陷伴根尖周炎的病例，在锥形束CT和显微镜辅助下行非手术治疗，随访1年，患牙无症状，根尖周病变明显缩小。.

Multiple research groups have consistently underscored the intricate interplay between the microbiome and apical periodontitis. However, the presence of variability in experimental design and quantitative assessment have added a layer of complexity, making it challenging to comprehensively assess the relationship. Through an unbiased methodological refinement analysis, we re-analyzed 4 microbiota studies including 120 apical samples from infected teeth (with/without root canal treatment), healthy teeth, using meta-analysis and machine learning. With high-performing machine-learning models, we discover disease signatures of related species and enriched metabolic pathways, expanded understanding of apical periodontitis with potential therapeutic implications. Our approach employs uniform computational tools across datasets to leverage statistical power and define a reproducible signal potentially linked to the development of secondary apical periodontitis (SAP).

OBJECTIVE: Autophagy is involved in human apical periodontitis (AP). However, it is not clear whether autophagy is protective or destructive in bone loss via the receptor activator of nuclear factor-κB ligand (RANKL)/RANK/osteoprotegerin (OPG) axis. This study aimed to investigate the involvement of autophagy via the RANKL/RANK/OPG axis during the development of AP in an experimental rat model.
METHODS: Twenty-four female Sprague-Dawley rats were divided into control, experimental AP (EAP) + saline, and EAP + 3-methyladenine (An autophagy inhibitor, 3-MA) groups. The control group did not receive any treatment. The EAP + saline group and the EAP + 3-MA group received intraperitoneal injections of saline and 3-MA, respectively, starting 1 week after the pulp was exposed. Specimens were collected for microcomputed tomography (micro-CT) scanning, histological processing, and immunostaining to examine the expression of light chain 3 beta (LC3B), RANK, RANKL, and OPG. Data were analysed using one-way analysis of variance (p < .05).
RESULTS: Micro-CT showed greater bone loss in the EAP + 3-MA group than in the EAP + saline group, indicated by an elevated trabecular space (Tb.Sp) (p < .05). Inflammatory cell infiltration was observed in the EAP + saline and EAP + 3-MA groups. Compared with EAP + saline group, the EAP + 3-MA group showed weaker expression of LC3B (p < .01) and OPG (p < .05), more intense expression of RANK (p < .01) and RANKL (p < .01), and a higher RANKL/OPG ratio (p < .05).
CONCLUSIONS: Autophagy may exert a protective effect against AP by regulating the RANKL/RANK/OPG axis, thereby inhibiting excessive bone loss.

BACKGROUND: Often there is the need of moving endodontically treated teeth. Orthodontic movement may have no effect on the prognosis of teeth with root canal treatment (RCT). To verify this subject, we evaluated the effect of orthodontic movement on the prognosis of RCT teeth using cone-beam computed tomography (CBCT) and further explored the influence of orthodontic movement on the prognosis of RCT teeth with and without apical periodontitis (AP).
METHODS: This retrospective study was conducted by evaluating 169 RCT teeth of 100 patients who had undergone fixed orthodontic treatment. AP was assessed and classified using the CBCT periapical index. Univariate analysis of RCT outcome was performed for the total RCT group, RCT without AP group and RCT with AP group. Multivariate logistic regression was performed for the total RCT group and RCT without AP group, respectively, but not for the RCT with AP group. Variables related to the prognosis of RCT were included, such as age, gender, tooth position, RCT quality, coronal restoration quality, periodontal condition, orthodontic traction distance, and orthodontic rotation angle.
RESULTS: The orthodontic traction distance and rotation angle were not significantly correlated to the RCT outcomes, regardless of the presence of AP. Among the total RCT group, teeth with unqualified RCT (odds ratio = 3.42, P = .004) and inadequate coronal restoration (odds ratio = 4.40, P = .031) had a lower success rate. Of the 97 RCT teeth without AP, unqualified RCT was a risk factor for treatment failure (odds ratio = 3.55, P = .041). Of the 72 RCT teeth with AP, the univariate analysis showed that RCT quality were significantly related to the outcome (P = .042).
CONCLUSIONS: Orthodontic movement had no effect on the prognosis of RCT teeth regardless of the presence of AP.