OBJECTIVE: Apical periodontitis is an inflammatory disorder triggered by an immune response to bacterial infection, leading to the periapical tissue damage and alveolar resorption. However, the underlying mechanisms driving this process remain elusive, due to the complex and interconnected immune microenvironment within the local lesion site. In this study, the influence of Nlrp3 inflammasome-mediated immune response on the apical periodontitis was investigated.
METHODS: RNA sequencing, immunohistochemistry and ELISA assay were performed to investigate the activation of Nlrp3 inflammasome signalling pathways in the human periapical tissues, including radicular cysts, periapical granulomas and healthy oral mucosa. A mouse model of apical periodontitis was established to study the role of Nlrp3 knockout in periapical bone resorption and Treg cell stability, and the underlying mechanism was explored through in vitro experiments. In vivo Treg cell adoptive transfer was performed to investigate the effects of Treg cells on the progression of apical periodontitis.
RESULTS: Our findings find that the hyperactivated Nlrp3 inflammasome is present in human periapical lesions and plays a vital role in the immune-related periapical bone loss. Using a mouse model of apical periodontitis, we observe that Nlrp3 deficiency is resistant to bone resorption. This protection was accompanied by elevated generation and infiltration of local Treg cells that displayed a notable ability to suppress RANKL-dependent osteoclast differentiation. In terms of the mechanism of action, Nlrp3 deficiency directly inhibits the osteoclast differentiation and bone loss through JNK/MAPK and NF-κB pathways. In addition, Nlrp3 induces pyroptosis in the stem cells from apical papilla (SCAPs), and the subsequent release of cytokines affects the stability of Treg cell in periapical lesions, leading indirectly to enhanced bone resorption. In turn, adoptive transfer of both Nlrp3-deficient and wild-type Treg cells effectively prevent the bone erosion during apical periodontitis.
CONCLUSIONS: Together, our data identify that the Nlrp3 inflammasome modulates the Treg cell stability and osteoclastogenesis in the periapical inflammatory microenvironment, thus determining the progression of bone erosion.

UNASSIGNED: The aim of the current study was to identify the expression of P63 and its relation to odontogenic epithelial cell proliferation, severity of the inflammatory infiltrate and size of radicular cysts (RCs).
UNASSIGNED: In this retrospective cross-sectional study, 30 cases of paraffin-embedded RCs were randomly selected from the archive. P63 and Ki-67 expression was assessed by immunohistochemistry.
UNASSIGNED: Epithelial P63 expression was absent in four (13.3%), weak in 10 (33.3%), and moderate in 16 (53.3%) cases. In the connective tissue wall of RC, P63 expression was absent in two (6.7%) cases, weak in 24 (80.0%) cases, and moderate in four (13.3%) cases. Ki-67 was found to be weakly expressed in 12 (40.0%) cases, moderately expressed in 13 (43.3%), and strongly expressed in five (16.7%) cases. No correlation was found between Ki-67 expression in odontogenic epithelium and P63 expression in the odontogenic epithelium (rho = 0.110, p = .563) or fibrous capsule (rho = 0.160, p = .399). Nevertheless, we found a positive correlation between Ki-67 expression in the odontogenic epithelium and the size of the RC (rho = 0.450, p = .013). The inflammatory infiltrate was negatively correlated with P63 expression in the odontogenic epithelium (rho = -0.428, p = .018), and with the size of cysts (rho = -0.728, p < .001).
UNASSIGNED: There is a high expression of P63 throughout the odontogenic epithelium and connective tissue capsule of the RC. P63 expression in the odontogenic epithelium is negatively correlated with the degree of the inflammatory infiltrate but not with epithelial cell proliferation or the size of the cyst.

There is little knowledge about oxidative stress-induced senescence involvement in apical periodontitis. Here, we explored its molecular mechanism in periapical lesions.
Ten cases of radicular cysts and five cases of periapical granulomas were randomly selected. Immunohistochemical analysis was performed to detect the expression and correlation between Senescence-associated factor polymerase I and transcript release factor (PTRF) and Akt/FoxO1 signaling. Human periodontal ligament cells (hPDLCs) pretreated with LY294002 were exposed to H2O2-induced oxidative stress conditions and then cell proliferation, senescence, apoptosis, and associated signaling were evaluated by EdU labeling, β-galactosidase assay, RT-qPCR, and western blot analysis, respectively.
Polymerase I and transcript release factor and Akt/FoxO1 signaling were more frequently expressed in the radicular cyst than in periapical granulomas. Notably, cells in radicular cysts showed Akt activation, FoxO1 phosphorylation, and cytoplasmic translocation. In vitro, prominent H2O2-induced senescence was observed in hPDLCs. LY294002, a PI3K inhibitor, attenuated the expression levels of senescence (Klotho, P16INK4), apoptosis (Bad, Fas), phosphorylated Akt, and phosphorylated FoxO1; however, did not affect cell proliferation.
Our data indicated that senescence is present in clinical periapical lesions, and Akt/FoxO1 signaling is involved in the H2O2-induced cellular senescence, which could serve as a potential therapeutic target.

This study aimed to investigate the reliability and accuracy of high-resolution ultrasonography (US) for diagnosing periapical lesions and differentiating radicular cysts from granulomas.
This study included 109 teeth with periapical lesions of endodontic origin from 109 patients scheduled for apical microsurgery. Ultrasonic outcomes were analyzed and categorized after thorough clinical and radiographic examinations using US. B-mode US images reflected the echotexture, echogenicity, and lesion margin, while color Doppler US assessed the presence and features of blood flow of interested areas. Pathological tissue samples were obtained during apical microsurgery and subjected to histopathological examination. Fleiss\' κ was used to measure interobserver reliability. Statistical analyses were performed to assess the diagnostic validity and the overall agreement between US and histological findings. The reliability of US compared to histopathological examinations was assessed based on Cohen\'s κ.
The percent accuracy of US for diagnosing cysts, granulomas, and cysts with infection based on histopathological findings was 89.9%, 89.0%, and 97.2%, respectively. The sensitivity of US diagnoses was 95.1% for cysts, 84.1% for granulomas, and 80.0% for cysts with infection. The specificity of US diagnoses was 86.8% for cysts, 95.7% for granulomas, and 98.1% for cysts with infection. The reliability for US compared to histopathological examinations was good (κ = 0.779).
The echotexture characteristics of lesions in US images correlated with their histopathological features. US can provide accurate information on the nature of periapical lesions based on the echotexture of their contents and the presence of vascularity. It can help improve clinical diagnosis and avoid overtreatment of patients with apical periodontitis.

BACKGROUND: Radicular cysts are one of the most common odontogenic cystic lesions found in the jaw. Nonsurgical treatment of large radicular cysts is a topic of ongoing debate, and there is still no clear consensus on the most effective therapies. The apical negative pressure irrigation system aspirates the cystic fluid and releases the static pressure in the radicular cyst, representing a minimally invasive approach for decompression. In this case, the radicular cyst was in close proximity to the mandibular nerve canal. We used nonsurgical endodontic treatment with a homemade apical negative pressure irrigation system and the prognosis was good.
METHODS: A 27-year-old male presented to our Department of General Dentistry with complaints of pain in the mandibular right molar when chewing. The patient had no history of drug allergies or systemic disease. A multidisciplinary management approach was designed and included root canal retreatment with a homemade apical negative pressure irrigation system, deep margin elevation and prosthodontic treatment. According to a 1-year follow-up period, the patient showed a favorable outcome.
CONCLUSIONS: This report reveals that nonsurgical treatment with an apical negative pressure irrigation system may provide new insights into the treatment of radicular cysts.

BACKGROUND: Bone loss is strongly associated with the immunologic milieu in apical periodontitis (AP). Tertiary lymphoid structures (TLSs) are organized lymphoid cell aggregates that form in nonlymphoid tissues under persistent inflammatory circumstances. To date, there has been no relevant report of TLSs in periapical lesions. This work aimed to investigate the formation and potential function of TLSs in AP.
METHODS: Tissues from human apical lesions (n = 61) and healthy oral mucosa (n = 5) were collected. Immunohistochemistry and multiplex immunofluorescence were used to detect the formation of TLSs. Correlation analyses were performed between clinical variables and TLSs. In addition, immunohistochemistry was used to evaluate the expression of interleukin-1 beta, interleukin-6, receptor activator of nuclear factor kappa-B ligand, and macrophage subsets in the apical lesions.
RESULTS: Periapical granulomas (n = 24) and cysts (n = 37) were identified by histologic evaluation. TLSs, composed of B-cell and T-cell clusters, developed in periapical granulomas and radicular cysts. The CXC-chemokine ligand 13, its receptor CXC-chemokine receptor 5, follicular dendritic cells, and high endothelial venules were localized in TLSs. The quantity and size of TLSs were positively associated with bone loss in AP. Moreover, proinflammatory cytokines and macrophage subsets were also substantially elevated in TLS regions of apical lesions.
CONCLUSIONS: The formation of TLSs in periapical granulomas and cysts was closely associated with persistent immune responses and bone loss in apical lesions. TLSs provide an updated insight into the complicated immune response process in AP.

Palatal radicular groove is a developmental malformation of maxillary incisors, lateral incisors in particular, which often causes periodontal destruction. This paper reports a case of combined periodontal-endodontic lesions induced by palatal radicular groove, which was initially misdiagnosed as a simple periapical cyst. After root canal therapy and periapical cyst curettage, the course of disease was prolonged, resulting in the absence of buccal and maxillary bone plates in the affected tooth area. After the etiology was determined, the affected tooth was extracted and guide bone tissue regeneration was performed at the same time, followed by implantation and restoration at the later stage, leading to clinical cure. The palatal radicular groove is highly occult, and the clinical symptoms are not typical. If the abscess of the maxillary lateral incisor occurs repeatedly, and the abscess of the maxillary lateral incisor has not been cured after periodontal and root canal treatment, cone-beam computed tomographic and periodontal flap surgery should be considered.
畸形舌侧沟是上颌切牙尤其是侧切牙常见的发育畸形，常引起牙周组织的破坏。本文报告1例畸形舌侧沟引发的牙周-牙髓联合病变误诊为单纯的根尖周囊肿的病例，经完善根管治疗及根尖周囊肿刮除术后病程迁延不愈，造成患牙区域颊、颚侧骨板缺如，后通过拔除患牙同期行位点保存术，后期配合种植修复，得到临床治愈。畸形舌侧沟隐匿性强、临床表现往往不典型，如有上颌侧切牙脓包反复发作或深牙周袋持续存在，应完善影像学检查，必要时行牙周翻瓣术探查牙根面形态。.

Squamous cell carcinomas (SCCs) are common malignant tumors in the oral and maxillofacial region. However, SCCs secondary to marsupialization of odontogenic radicular cysts are extremely rare. The authors report an unusual case of a 43-year-old male presented with dull pain in the right molar region of the mandible without numbness of lower lips, who had a long history of smoking, alcohol consumption, and betel nut chewing. Computerized tomography revealed a round well-defined unilocular radiolucent at the apex of lower right premolars, 2 nonvital teeth. The clinical diagnosis was the radicular cyst of the right mandible. The patient was initially treated with root canal therapy of the teeth followed by marsupialization with a mandibular vestibular groove incision. While the patient did not follow the instruction of irrigation of the cyst and had no regular follow-up. The reexamination of computerized tomography indicated a round well-defined unilocular radiolucent at the apex of lower right premolars and filled with a soft tissue without clear boundary with buccal muscles at 31 months follow-up. There were no masses or ulcer around the mandibular vestibular groove incision and the patient had no sign of numbness of lower lips. The clinical diagnosis was the radicular cyst of right mandible with infection. A curettage was performed. However, the pathologic diagnosis was well-differentiated SCC. An extended radical surgical resection including segmental resection of the right mandible was performed. The histopathology was well-differentiated SCC without the cyst epithelium and invasion of bone, which can be distinguished from primary intraosseous SCC. The case indicates that marsupialization performed in patients with a history of smoking, alcohol consumption, and betel nut chewing, has a risk of suffering from oral SCC.

OBJECTIVE: As a key DNA sensor, cyclic GMP-AMP synthase (cGAS) has emerged as a major mediator of innate immunity and inflammation. Human apical periodontitis has yet to be studied for the presence of cGAS. This investigation was conducted to determine if cGAS is involved in the pathological process of human apical periodontitis.
METHODS: Sixty four human periapical lesions, comprising 20 periapical granulomas and 44 radicular cysts, were employed in this investigation. Healthy gingiva (n = 6), dental pulp (n = 3), and apical papilla (n = 3) were used as control samples. The expression of cGAS in the periapical tissues was discovered using immunohistochemical staining. mRNA-Sequencing and qRT-PCR were utilized to determine the differentially expressed genes (DEGs) associated with DNA-sensing signalling in periapical lesions compared to the healthy control. Immunofluorescence labelling was used to identify the co-expression of cGAS, interleukin-1β, and interleukin-18.
RESULTS: A significantly greater expression level of cGAS was discovered in the periapical lesions, with no significant difference between radicular cysts and periapical granulomas. mRNA-Sequencing analysis and qRT-PCR identified differentially expressed mRNA, such as cGAS and its downstream DEGs, between periapical lesions and healthy control tissues. Immunofluorescence labelling further revealed that cGAS, interleukin-1, and interleukin-18 were co-localized.
CONCLUSIONS: These observations imply that along with the synthesis of interleukin-1 and interleukin-18, cGAS may be involved in the aetiology of apical periodontitis.

Implant periapical lesion (IPL), as a peri-implant disease originating from implant apex, maintains coronal osseointegration in the early stage. With the understanding to IPL increasingly deepened, IPL classification based on different elements was proposed although there still lacks an overall classification system. This study, aiming to systematically integrate the available data published in the literature on IPL associated with histopathology, proposed a comprehensive classification framework and treatment decision tree for IPL.
English articles on the topic of \"implant periapical lesion\", \"retrograde peri-implantitis\" and \"apical peri-implantitis\" were searched on PubMed, Embase and Web of Science from 1992 to 2021, and citation retrieval was performed for critical articles. Definite histopathology and radiology of IPL are indispensable criteria for including the article in the literature. The protocol was registered in PROSPERO (CRD42022378001). A total of 509 papers identified, 28 studies were included in this review. In only one retrospective study, 37 of 39 IPL were reported to be at the inflammatory or abscess stage. 27 cases (37 implants) were reported, including acute non-suppurative (1/37, developed to chronic granuloma), chronic granuloma (5/37), acute suppurated (2/37), chronic suppurated-fistulized (6/37), implant periapical cyst (21/37), poor bone healing (2/37), foreign body reaction (1/37). Antibiotics alone did not appear to be effective, and the consequence of surgical debridement required cautious interpretation because of the heterogeneity of lesion course and operation. Implant apicoectomy and marsupialization were predictable approaches in some cases.
The diversiform nature of IPL in the case reports confirms the need for such histopathological classification, which may enhance the comparison and management of different category.