Notch - a possible mediator between Epstein-Barr virus infection and bone resorption in apical periodontitis.
- 作者列表："Jakovljevic A","Nikolic N","Carkic J","Andric M","Miletic M","Beljic-Ivanovic K","Jovanovic T","Milasin J
:Objectives: This study aimed to investigate whether Epstein-Barr virus (EBV) positive periapical lesions exhibited higher mRNA levels of Notch signalling molecules (Notch2 and Jagged1), bone resorption regulators (receptor activator of nuclear factor kappa-β ligand (RANKL) and osteoprotegerin (OPG)), and proinflammatory cytokines (tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6) compared to EBV negative lesions. Additionally, the potential correlation between investigated molecules in periapical lesions was analyzed.Materials and methods: Sixty-four apical periodontitis lesions were obtained subsequent to standard apicoectomy procedure. The presence of EBV was determined using nested PCR. Based on the presence of EBV all periapical lesions were divided into two groups, 29 EBV positive and 35 EBV negative lesions. A reverse transcriptase real-time PCR was used to determine mRNA levels of Notch2, Jagged1, RANKL, OPG, TNF-α, IL-1β and IL-6.Results: Significantly higher mRNA levels of Notch2, Jagged1, RANKL and IL-1β were observed in EBV positive compared to EBV negative lesions. Significant positive correlation was present between Notch2 and Jagged1, Jagged1 and RANKL, and IL-β and TNF-α in EBV positive periapical lesions.Conclusions: Notch signalling pathway may be involved in alveolar bone resorption in apical periodontitis lesions infected by EBV.
目的: 本研究旨在探讨Epstein-Barr病毒 (EBV) 阳性根尖周病变是否表现出较高的Notch信号分子 (Notch2 和Jagged1) mRNA水平。骨吸收调节因子 (核因子 κ-β 受体活化因子配体 (RANKL) 和骨保护素 (OPG)) 和促炎细胞因子 (肿瘤坏死因子-α (TNF-α))，Interleukin-1 β (il-1 β) 和IL-6) 比拟EBV阴性病灶。此外，分析了根尖周病变中研究分子之间的潜在相关性。材料和方法: 标准根尖切除术后获得 64 个根尖周炎病变。使用巢式PCR确定EBV的存在。根据有无EBV，将所有根尖周病变分为两组，EBV阳性病变 29 例，EBV阴性病变 35 例。使用逆转录酶实时PCR测定Notch2 、Jagged1 、RANKL、OPG、TNF-α 、il-1 β 和IL-6.Results的mRNA水平: Notch2 、Jagged1 、与EBV阴性病变相比，在EBV阳性病变中观察到RANKL和il-1 β。在EBV阳性根尖周病变中，Notch2 与Jagged1 、Jagged1 与RANKL、il-1 β 与TNF-α 呈显著正相关。结论: Notch信号通路可能参与了EBV感染根尖周炎的牙槽骨吸收。
METHODS:BACKGROUND:The anterior oronasal fistulae neighboring the alveolar cleft could persist or reappear after the alveolar reconstruction with cancellous bone grafting. The persistent symptomatic anterior oronasal fistulae need to be repaired, but surgery remains a challenge in cleft care. Surprisingly, this issue has rarely been reported in the literature. The purpose of this long-term study was to report a single surgeon experience with a therapeutic protocol for persistent symptomatic anterior oronasal fistula repair. METHODS:This is a retrospective study of consecutive patients with Veau type III and IV clefts and persistent symptomatic anterior oronasal fistulae managed according to a therapeutic protocol from 1997 to 2018. Depending on fistula size, patients were treated with local flaps associated with an interpositional graft or two-stage tongue flaps (small/medium or large fistulae, respectively). The surgical outcomes were classified as "good" (complete fistula closure with no symptoms), "fair" (asymptomatic narrow fistula remained), or "poor" (failure with persistent symptoms). RESULTS:Forty-four patients with persistent symptomatic anterior oronasal fistulae were reconstructed with local flaps associated with interpositional fascia or dermal fat grafting (52.3%) or two-stage tongue flaps (47.7%). Most of patients (93.2%) presented "good" outcomes, ranging from 87% to 100% (local and tongue flaps, respectively). Three (6.8%) patients presented symptomatic residual fistula ("poor" outcomes). CONCLUSIONS:For the repair of persistent symptomatic anterior oronasal fistulae, this therapeutic protocol provided satisfactory outcome with low fistula recurrence rate.
METHODS:OBJECTIVE:Methadone is a vital treatment for women with opioid use disorder in pregnancy. Previous reports suggested an association between methadone exposure and Pierre Robin sequence (PRS), a rare craniofacial anomaly. We assessed the association between gestational methadone exposure and PRS. DESIGN/SETTING:This case-malformed control study used European Surveillance of Congenital Anomalies population-based registries in Ireland, the Netherlands, Italy, Switzerland, Croatia, Malta, Portugal, Germany, Wales, Norway and Spain, 1995-2011. PATIENTS:Cases included PRS based on International Classification of Disease (ICD), Ninth Edition-British Paediatric Association (BPA) code 75 603 or ICD, Tenth Edition-BPA code Q8708. Malformed controls were all non-PRS anomalies, excluding genetic conditions, among live births, fetal deaths from 20 weeks' gestation and terminations of pregnancy for fetal anomalies. An exploratory analysis assessed the association between methadone exposure and other congenital anomalies (CAs) excluding PRS. Methadone exposure was ascertained from medical records and maternal interview. RESULTS:Among 87 979 CA registrations, there were 127 methadone-exposed pregnancies and 336 PRS cases. There was an association between methadone exposure and PRS (OR adjusted for registry 12.3, 95% CI 5.7 to 26.8). In absolute terms, this association reflects a risk increase from approximately 1-12 cases per 10 000 births. A raised OR was found for cleft palate (adjusted OR 5.0, 95% CI 2.7 to 9.2). CONCLUSIONS:These findings suggest that gestational methadone exposure is associated with PRS. The association may be explained by unmeasured confounding factors. The small increased risk of PRS in itself does not alter the risk-benefit balance for gestational methadone use. The association with cleft palate, a more common CA, should be assessed with independent data.
METHODS::Orthopedic treatment to improve deficient maxillary growth of cleft lip and palate patients is an important part of treatment. The success of this treatment is strongly dependent on the time of initiation of therapy. There has been a large controversy in the available literature regarding the skeletal age of these patients. The aim of the present study was to compare the skeletal age of cleft lip and palate patients with normal individuals.37 unilateral and 14 bilateral cleft lip and palate patients and 47 healthy individuals participated in this cross-sectional study. The patients were classified into 8 to 10 and 11 to 14-year-old individuals. Cervical vertebral maturational stage of participants was evaluated in the lateral cephalometry. The skeletal age of cleft lip and palate patients was compared with normal controls. Chi-square was used for statistical analysis. There was not a significant difference in the skeletal developmental stage of unilateral and bilateral cleft compared to their normal peers according to their age and sex. Also, significant difference in skeletal maturational stage of cleft lip and palate patients was not found between boys and girls (P = 0.8). Similarly, no significant difference was found in the skeletal age of the 3 studied groups without considering the age and sex of participants (P = 0.5). Regarding the similar skeletal maturational stage of cleft lip and palate patients with normal controls in our study, their maxillofacial orthopedic treatment can be initiated at similar time to normal peers.