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Effect of Periodontitis and Periodontal Therapy on Oral and Gut Microbiota. 牙周炎和牙周治疗对口腔和肠道微生物群的影响
Pub Date : 2024-04-01 Epub Date: 2024-02-16 DOI: 10.1177/00220345231222800
G Baima, I Ferrocino, V Del Lupo, E Colonna, V Thumbigere-Math, G P Caviglia, I Franciosa, G M Mariani, M Romandini, D G Ribaldone, F Romano, M Aimetti

Mounting evidence indicates that periodontitis-related oral bacteria may contribute to gut microbial dysbiosis. This clinical study aimed to explore the oral-gut microbial signatures associated with periodontitis and to longitudinally evaluate the effect of periodontal treatment on the oral and gut microbial composition. Stool and saliva samples from generalized stage III/IV periodontitis patients (n = 47) were collected and analyzed by 16S ribosomal RNA gene amplicon sequencing, before and 3 mo after steps I to II of periodontal therapy. Periodontally healthy matched subjects (n = 47) were used as controls. Principal component analysis was carried out to identify oral-gut microbial profiles between periodontitis patients at baseline and healthy subjects; periodontitis samples were longitudinally compared before and after treatment. β-Diversity of gut microbial profiles of periodontitis patients before treatment significantly differed from healthy controls (P < 0.001). Periodontal therapy was associated with a significant change in gut microbiota (P < 0.001), with post-treatment microbial profiles similar to healthy volunteers. A higher abundance of Bacteroides, Faecalibacterium, Fusobacterium, and Lachnospiraceae was noted in fecal samples of periodontitis patients at baseline compared to healthy controls. In contrast, Lactobacillus was the only genus more abundant in the latter. Additionally, periodontal therapy led to a parallel reduction in the salivary carriage of periodontal pathobionts, as well as gut Bacteroides, Lachnoclostridium, Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae, to levels similar to healthy controls. Collectively, discriminating oral-gut microbial signatures of periodontitis were found. Periodontal treatment both mitigated oral dysbiosis and altered gut microbial composition, signifying potential broader implications for gastrointestinal health and disease.

越来越多的证据表明,与牙周炎相关的口腔细菌可能会导致肠道微生物菌群失调。这项临床研究旨在探索与牙周炎相关的口腔-肠道微生物特征,并纵向评估牙周治疗对口腔和肠道微生物组成的影响。研究人员收集了全身性 III/IV 期牙周炎患者(n = 47)的粪便和唾液样本,并在牙周治疗步骤 I 至 II 之前和之后 3 个月对样本进行了 16S 核糖体 RNA 基因扩增片段测序分析。牙周健康的匹配受试者(47 人)作为对照。进行主成分分析以确定牙周炎患者基线与健康受试者之间的口腔肠道微生物特征;对治疗前后的牙周炎样本进行纵向比较。治疗前牙周炎患者肠道微生物图谱的 β-多样性与健康对照组有显著差异(P < 0.001)。牙周治疗与肠道微生物群的显著变化有关(P < 0.001),治疗后的微生物图谱与健康志愿者相似。与健康对照组相比,牙周炎患者的粪便样本中乳酸杆菌、粪杆菌、镰刀菌和漆树菌的丰度较高。相比之下,乳酸杆菌是后者中唯一较多的菌属。此外,牙周治疗也会导致牙周致病菌的唾液携带量以及肠道乳杆菌属、拉氏菌属、拉氏ospiraceae、Oscillospiraceae 和 Ruminococcaceae 的唾液携带量减少,达到与健康对照组相似的水平。总之,我们发现了牙周炎的口腔-肠道微生物特征。牙周治疗既缓解了口腔菌群失调,又改变了肠道微生物组成,这对胃肠道健康和疾病具有潜在的广泛影响。
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引用次数: 0
Neighborhood Deprivation and Changes in Oral Health in Older Age: A Longitudinal Population-Based Study. 邻里贫困与老年人口腔健康的变化:基于人口的纵向研究。
Pub Date : 2024-04-01 Epub Date: 2024-02-27 DOI: 10.1177/00220345231224337
S G Ganbavale, E Papachristou, J C Mathers, A O Papacosta, L T Lennon, P H Whincup, S G Wannamethee, S E Ramsay

The aim of this study was to examine the extent to which neighborhood-level socioeconomic factors (objective and perceived) are associated with poor oral health in older adults over time, independent of individual socioeconomic position. Data for this cross-sectional and longitudinal observation study came from a socially and geographically representative cohort of men aged 71 to 92 y in 2010-12 (n = 1,622), drawn from British general practices, which was followed up in 2018-19 (aged 78-98 y; N = 667). Dental measures at both times included number of teeth, periodontal pocket depth, self-rated oral health, and dry mouth. Neighborhood deprivation was based on Index of Multiple Deprivation (IMD) and a cumulative index measuring perceptions about local environment. Individual-level socioeconomic position was based on longest-held occupation. Multilevel and multivariate logistic regressions, adjusted for relevant sociodemographic, behavioral, and health-related factors, were performed to examine the relationships of dental measures with IMD and perceived neighborhood quality index, respectively. Cross-sectionally, risks of tooth loss, periodontal pockets, and dry mouth increased from IMD quintiles 1 to 5 (least to most deprived); odds ratios (ORs) for quintile 5 were 2.22 (95% confidence interval [CI], 1.41-3.51), 2.82 (95% CI, 1.72-4.64), and 1.51 (95% CI, 1.08-2.09), respectively, after adjusting for sociodemographic, behavioral, and health-related factors. Risks of increased pocket depth and dry mouth were significantly greater in quintile 5 (highest problems) of perceived neighborhood quality index compared to quintile 1. Over the 8-y follow-up, deterioration of dentition (tooth loss) was significantly higher in the most deprived IMD quintiles after full adjustment (OR for quintile 5 = 2.32; 95% CI, 1.09-4.89). Deterioration of dentition and dry mouth were significantly greater in quintile 5 of perceived neighborhood quality index. Neighborhood-level factors were associated with poor oral health in older age, both cross-sectionally and longitudinally, particularly with tooth loss, and dry mouth, independent of individual-level socioeconomic position.

本研究的目的是探讨邻里层面的社会经济因素(客观的和感知的)在多大程度上与老年人长期的口腔健康状况不良有关,而与个人的社会经济地位无关。这项横断面和纵向观察研究的数据来自一个具有社会和地理代表性的队列,该队列中的男性在2010-12年间的年龄为71至92岁(n=1622),他们来自英国的全科诊所,该队列在2018-19年间接受了随访(年龄为78至98岁;n=667)。这两个时间段的牙科测量指标包括牙齿数量、牙周袋深度、口腔健康自评和口干。邻里贫困程度基于多重贫困指数(IMD)和衡量当地环境感知的累积指数。个人层面的社会经济地位基于从事时间最长的职业。在对相关的社会人口、行为和健康相关因素进行调整后,分别进行了多层次和多变量逻辑回归,以检验牙科指标与多重贫困指数(IMD)和感知邻里质量指数之间的关系。从横截面来看,牙齿脱落、牙周袋和口干的风险从IMD五分位数1到5(从最贫困到最贫困)依次增加;调整社会人口、行为和健康相关因素后,五分位数5的几率比(ORs)分别为2.22(95% 置信区间[CI],1.41-3.51)、2.82(95% CI,1.72-4.64)和1.51(95% CI,1.08-2.09)。与五分位数 1 相比,五分位数 5(问题最多)的感知邻里质量指数出现牙周袋深度增加和口干的风险明显更高。在 8 年的随访中,经过全面调整后,最贫困的 IMD 五分位数人群的牙质恶化(牙齿脱落)程度明显更高(五分位数 5 的 OR = 2.32;95% CI,1.09-4.89)。在感知邻里质量指数的五分位数中,牙质恶化和口干的程度明显更高。无论从横向还是纵向来看,邻里层面的因素都与老年人口腔健康状况不佳有关,尤其是与牙齿脱落和口干有关,与个人层面的社会经济地位无关。
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引用次数: 0
In Situ Photo-Crosslinkable Protein Bioadhesive for Bone Graft Fixation. 用于骨移植固定的原位光交联蛋白生物粘合剂
Pub Date : 2024-04-01 Epub Date: 2024-02-05 DOI: 10.1177/00220345231224709
J Yun, I H Nam, H Lee, Y K Jo, H Lee, S H Jun, H J Cha

Bone grafting is a fundamental dental surgery procedure widely used for implant placement and periodontal disease management treatments. Despite its broad applications, vertical bone augmentation presents unique challenges, including the risk of graft displacement due to gravitational and masticatory forces. Traditional physical stabilization methods introduce additional complexities and risks, underscoring the need for innovative fixation technologies. This study aimed to develop an in situ photo-crosslinkable bioadhesive hydrogel (iPBAH) as a multifunctional bone graft binder to enhance the process of bone reconstruction. The bioadhesive is composed of mussel-derived adhesive protein (MAP) fused with the cell-adhesive peptide RGD. The numerous tyrosine residues in MAP facilitate rapid photo-crosslinking, enabling efficient hydrogel formation using visible blue light. Subsequently, iPBAH underwent comprehensive characterization to evaluate its suitability as a multifunctional bone graft binder. iPBAH efficiently underwent in situ crosslinking through harmless exposure to visible light within minutes and displayed several exceptional properties, including a microporous structure, underwater adhesion, extended durability, high compressive strength, and biocompatibility. In vivo assessments, using male Sprague-Dawley rats, demonstrated that iPBAH binder significantly enhanced bone regeneration in a rat calvarial bone defect model. The in situ crosslinking of the iPBAH binder during bone graft transplantation can effectively fill irregular and complex defect shapes while simultaneously preventing graft material leakage. The improved physical attributes of the bound graft material can enhance its resistance to external forces, thereby ensuring sustained retention over time. Moreover, the interaction between iPBAH and surrounding tissues promotes adhesion and integration of the graft material with host tissues in the defect area. In addition, the included RGD peptide in iPBAH can augment inherent cell recruitment, adhesion, and growth, consequently expediting osteogenesis.

植骨是一种基本的牙科手术方法,广泛用于种植体植入和牙周病治疗。尽管应用广泛,但垂直骨增量术也面临着独特的挑战,包括因重力和咀嚼力而导致移植骨移位的风险。传统的物理稳定方法带来了额外的复杂性和风险,突出了对创新固定技术的需求。本研究旨在开发一种原位光交联生物粘合剂水凝胶(iPBAH),作为一种多功能骨移植物粘合剂,以改善骨重建过程。这种生物粘合剂由贻贝源粘合蛋白(MAP)与细胞粘合肽 RGD 融合而成。MAP 中的大量酪氨酸残基有助于快速光交联,从而在可见蓝光下高效形成水凝胶。iPBAH 可在数分钟内通过无害的可见光照射实现原位交联,并显示出多种优异特性,包括微孔结构、水下粘附性、持久性、高抗压强度和生物相容性。使用雄性 Sprague-Dawley 大鼠进行的体内评估表明,iPBAH 粘合剂可显著促进大鼠腓骨缺损模型中的骨再生。在骨移植过程中,iPBAH 粘合剂的原位交联可有效填充不规则和复杂的缺损形状,同时防止移植材料渗漏。粘合后的移植物材料物理属性得到改善,可增强其抵抗外力的能力,从而确保长期的持续保留。此外,iPBAH 与周围组织的相互作用还能促进移植材料与缺损区域宿主组织的粘附和整合。此外,iPBAH 中的 RGD 肽还能增强固有细胞的募集、粘附和生长,从而加快成骨过程。
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引用次数: 0
Response to Letter, "Autophagy Plays a Crucial Role in Ameloblast Differentiation". 对题为 "自噬在釉母细胞分化中发挥关键作用 "的信件的回复
Pub Date : 2024-04-01 Epub Date: 2024-02-21 DOI: 10.1177/00220345241231770
C Iwaya, J Iwata
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引用次数: 0
Heterogeneous Association of Tooth Loss with Functional Limitations. 牙齿缺失与功能限制的异质性关联
Pub Date : 2024-04-01 DOI: 10.1177/00220345241226957
Y Matsuyama, J Aida, K Kondo, K Shiba

Tooth loss is prevalent in older adults and associated with functional capacity decline. Studies on the susceptibility of some individuals to the effects of tooth loss are lacking. This study aimed to investigate the heterogeneity of the association between tooth loss and higher-level functional capacity in older Japanese individuals employing a machine learning approach. This is a prospective cohort study using the data of adults aged ≥65 y in Japan (N = 16,553). Higher-level functional capacity, comprising instrumental independence, intellectual activity, and social role, was evaluated using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC). The scale ranged from 0 (lowest function) to 13 (highest function). Doubly robust targeted maximum likelihood estimation was used to estimate the population-average association between tooth loss (having <20 natural teeth) and TMIG-IC total score after 6 y. The heterogeneity of the association was evaluated by estimating conditional average treatment effects (CATEs) using the causal forest algorithm. The result showed that tooth loss was statistically significantly associated with lower TMIG-IC total scores (population-average effect: -0.14; 95% confidence interval, -0.18 to -0.09). The causal forest analysis revealed the heterogeneous associations between tooth loss and lower TMIG-IC total score after 6 y (median of estimated CATEs = -0.13; interquartile range = 0.12). The high-impact subgroup (i.e., individuals with estimated CATEs of the bottom 10%) were significantly more likely to be older and male, had a lower socioeconomic status, did not have a partner, and had poor health conditions compared with the low-impact subgroup (i.e., individuals with estimated CATEs of the top 10%). This study found that heterogeneity exists in the association between tooth loss and lower scores on functional capacity. Implementing tooth loss prevention policy and clinical measures, especially among vulnerable subpopulations significantly affected by tooth loss, may reduce its burden more effectively.

牙齿脱落在老年人中很普遍,并与机能下降有关。目前还缺乏关于某些人对牙齿脱落影响的易感性的研究。本研究采用机器学习方法,旨在调查日本老年人牙齿脱落与高级功能能力之间关系的异质性。这是一项前瞻性队列研究,使用的是日本年龄≥65 岁成年人的数据(N = 16,553 人)。研究使用东京都老年学研究所能力指数(TMIG-IC)对老年人的高级功能能力(包括工具独立性、智力活动和社会角色)进行了评估。该指数从 0(最低功能)到 13(最高功能)不等。采用双稳健目标最大似然估计法来估算牙齿缺失(有牙齿)与社会角色之间的人群平均关联。
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引用次数: 0
The Essential Role of Proteoglycans and Glycosaminoglycans in Odontogenesis. 蛋白聚糖和糖胺聚糖在牙齿生成过程中的重要作用
Pub Date : 2024-04-01 Epub Date: 2024-02-26 DOI: 10.1177/00220345231224228
J Chen, T Sun, B Lin, B Wu, J Wu

Tooth development and regeneration are regulated through a complex signaling network. Previous studies have focused on the exploration of intracellular signaling regulatory networks, but the regulatory roles of extracellular networks have only been revealed recently. Proteoglycans, which are essential components of the extracellular matrix (ECM) and pivotal signaling molecules, are extensively involved in the process of odontogenesis. Proteoglycans are composed of core proteins and covalently attached glycosaminoglycan chains (GAGs). The core proteins exhibit spatiotemporal expression patterns during odontogenesis and are pivotal for dental tissue formation and periodontium development. Knockout of core protein genes Biglycan, Decorin, Perlecan, and Fibromodulin has been shown to result in structural defects in enamel and dentin mineralization. They are also closely involved in the development and homeostasis of periodontium by regulating signaling transduction. As the functional component of proteoglycans, GAGs are negatively charged unbranched polysaccharides that consist of repeating disaccharides with various sulfation groups; they provide binding sites for cytokines and growth factors in regulating various cellular processes. In mice, GAG deficiency in dental epithelium leads to the reinitiation of tooth germ development and the formation of supernumerary incisors. Furthermore, GAGs are critical for the differentiation of dental stem cells. Inhibition of GAGs assembly hinders the differentiation of ameloblasts and odontoblasts. In summary, core proteins and GAGs are expressed distinctly and exert different functions at various stages of odontogenesis. Given their unique contributions in odontogenesis, this review summarizes the roles of proteoglycans and GAGs throughout the process of odontogenesis to provide a comprehensive understanding of tooth development.

牙齿的发育和再生是通过复杂的信号网络调控的。以往的研究侧重于细胞内信号调控网络的探索,但细胞外网络的调控作用直到最近才被揭示出来。蛋白聚糖是细胞外基质(ECM)的重要组成部分,也是关键的信号分子,广泛参与牙体发生过程。蛋白多糖由核心蛋白和共价连接的糖胺聚糖链(GAGs)组成。核心蛋白在牙体发生过程中呈现时空表达模式,是牙组织形成和牙周发育的关键。研究表明,敲除核心蛋白基因 Biglycan、Decorin、Perlecan 和 Fibromodulin 会导致釉质和牙本质矿化的结构缺陷。它们还通过调节信号转导密切参与牙周的发育和平衡。作为蛋白多糖的功能成分,GAGs 是一种带负电荷的无支链多糖,由带有不同硫酸化基团的重复二糖组成;它们为细胞因子和生长因子提供结合位点,以调节各种细胞过程。在小鼠中,牙上皮细胞缺乏 GAG 会导致牙齿胚芽发育的重启和超常门齿的形成。此外,GAGs 对牙齿干细胞的分化至关重要。抑制 GAGs 的组装会阻碍成釉细胞和牙本质细胞的分化。总之,核心蛋白和GAGs在牙体发生的不同阶段表达不同,发挥不同的功能。鉴于它们在牙体发生过程中的独特贡献,本综述总结了蛋白多糖和 GAGs 在整个牙体发生过程中的作用,以提供对牙齿发育的全面认识。
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引用次数: 0
A Bilayer Method for Measuring Toughness and Strength of Dental Ceramics. 测量牙科陶瓷韧性和强度的双层法
Pub Date : 2024-04-01 Epub Date: 2024-02-27 DOI: 10.1177/00220345231225445
H Chai, J Russ, S Vardhaman, C H Lim, Y Zhang

The ever-increasing usage of ceramic materials in restorative dentistry necessitates a simple and effective method to evaluate flexural strength σF and fracture toughness KC. We propose a novel method to determine these quantities using a bilayer specimen composed of a brittle plate adhesively bonded onto a transparent polycarbonate substrate. When this bilayer structure is placed under spherical indentation, tunneling radial cracks initiate and propagate in the lower surface of the brittle layer. The failure analysis is based on previous theoretical relationships, which correlate σF with the indentation force P and layer thickness d, and KC with P and mean length of radial cracks. This work examines the accuracy and limitations of this approach using a wide range of contemporary dental ceramic materials. The effect of layer thickness, indenter radius, load level, and length and number of radial cracks are carefully examined. The accuracy of the predicted σF and KC is similar to those obtained with other concurrent test methods, such as biaxial flexure and 3-point bending (σF), and bending specimens with crack-initiation flaws (KC). The benefits of the present approach include treatment for small and thin plates, elimination of the need to introduce a precrack, and avoidance of dealing with local material nonlinearity effects for the KC measurements. Finally, the bilayer configuration resembles occlusal loading of a ceramic restoration (brittle layer) bonded to a posterior tooth (compliant substrate).

随着陶瓷材料在牙科修复中的应用日益广泛,需要一种简单有效的方法来评估抗弯强度 σF 和断裂韧性 KC。我们提出了一种新颖的方法,利用由粘接在透明聚碳酸酯基底上的脆性板组成的双层试样来确定这些量。当这种双层结构被置于球形压痕下时,隧道径向裂纹在脆性层的下表面开始并扩展。失效分析基于之前的理论关系,即 σF 与压入力 P 和层厚度 d 相关,KC 与 P 和径向裂纹平均长度相关。这项研究使用了多种当代牙科陶瓷材料,检验了这种方法的准确性和局限性。仔细研究了层厚、压头半径、载荷水平以及径向裂纹长度和数量的影响。预测的 σF 和 KC 的准确性与其他同时进行的测试方法相似,如双轴弯曲和三点弯曲 (σF),以及带有裂纹引发缺陷的弯曲试样 (KC)。本方法的优点包括:可处理小而薄的板材,无需引入预裂纹,以及在 KC 测量中避免处理局部材料非线性效应。最后,双层结构类似于将陶瓷修复体(脆性层)粘结到后牙(顺应性基底)上的咬合加载。
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引用次数: 0
IL-36 Regulates Neutrophil Chemotaxis and Bone Loss at the Oral Barrier. IL-36 在口腔屏障调节中性粒细胞趋化和骨质流失
Pub Date : 2024-04-01 Epub Date: 2024-02-27 DOI: 10.1177/00220345231225413
J Liu, H Meng, Y Mao, L Zhong, W Pan, Q Chen

Tissue-specific mechanisms regulate neutrophil immunity at the oral barrier, which plays a key role in periodontitis. Although it has been proposed that fibroblasts emit a powerful neutrophil chemotactic signal, how this chemotactic signal is driven has not been clear. The objective of this study was to investigate the site-specific regulatory mechanisms by which fibroblasts drive powerful neutrophil chemotactic signals within the oral barrier, with particular emphasis on the role of the IL-36 family. The present study found that IL-36γ, agonist of IL-36R, could promote neutrophil chemotaxis via fibroblast. Single-cell RNA sequencing data disclosed that IL36G is primarily expressed in human and mouse gingival epithelial cells and mouse neutrophils. Notably, there was a substantial increase in IL-36γ levels during periodontitis. In vitro experiments demonstrated that IL-36γ specifically activates gingival fibroblasts, leading to chemotaxis of neutrophils. In vivo experiments revealed that IL-36Ra inhibited the infiltration of neutrophils and bone resorption, while IL-36γ promoted their progression in the ligature-induced periodontitis mouse model. In summary, these data elucidate the function of the site-enriched IL-36γ in regulating neutrophil immunity and bone resorption at the oral barrier. These findings provide new insights into the tissue-specific pathophysiology of periodontitis and offer a promising avenue for prevention and treatment through targeted intervention of the IL-36 family.

组织特异性机制调节口腔屏障的中性粒细胞免疫,这在牙周炎中起着关键作用。尽管有人提出成纤维细胞会发出强大的中性粒细胞趋化信号,但这种趋化信号是如何驱动的还不清楚。本研究旨在探讨成纤维细胞在口腔屏障内驱动强大的中性粒细胞趋化信号的特定位点调控机制,特别强调了 IL-36 家族的作用。本研究发现,IL-36R的激动剂IL-36γ可通过成纤维细胞促进中性粒细胞趋化。单细胞 RNA 测序数据显示,IL36G 主要在人和小鼠牙龈上皮细胞及小鼠中性粒细胞中表达。值得注意的是,在牙周炎期间,IL-36γ的水平大幅上升。体外实验表明,IL-36γ 能特异性地激活牙龈成纤维细胞,导致中性粒细胞趋化。体内实验表明,在结扎诱导的牙周炎小鼠模型中,IL-36Ra 抑制了中性粒细胞的浸润和骨吸收,而 IL-36γ 则促进了它们的发展。总之,这些数据阐明了富集位点的IL-36γ在口腔屏障调节中性粒细胞免疫和骨吸收的功能。这些发现为牙周炎的组织特异性病理生理学提供了新的见解,并为通过有针对性地干预 IL-36 家族来预防和治疗牙周炎提供了一条很有前景的途径。
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引用次数: 0
Injectable Tissue-Specific Hydrogel System for Pulp-Dentin Regeneration. 用于牙髓-牙本质再生的可注射组织特异性水凝胶系统
Pub Date : 2024-04-01 Epub Date: 2024-02-27 DOI: 10.1177/00220345241226649
Y Han, J Xu, H Chopra, Z Zhang, N Dubey, W L Dissanayaka, J E Nör, M C Bottino

The quest for finding a suitable scaffold system that supports cell survival and function and, ultimately, the regeneration of the pulp-dentin complex remains challenging. Herein, we hypothesized that dental pulp stem cells (DPSCs) encapsulated in a collagen-based hydrogel with varying stiffness would regenerate functional dental pulp and dentin when concentrically injected into the tooth slices. Collagen hydrogels with concentrations of 3 mg/mL (Col3) and 10 mg/mL (Col10) were prepared, and their stiffness and microstructure were assessed using a rheometer and scanning electron microscopy, respectively. DPSCs were then encapsulated in the hydrogels, and their viability and differentiation capacity toward endothelial and odontogenic lineages were evaluated using live/dead assay and quantitative real-time polymerase chain reaction. For in vivo experiments, DPSC-encapsulated collagen hydrogels with different stiffness, with or without growth factors, were injected into pulp chambers of dentin tooth slices and implanted subcutaneously in severe combined immunodeficient (SCID) mice. Specifically, vascular endothelial growth factor (VEGF [50 ng/mL]) was loaded into Col3 and bone morphogenetic protein (BMP2 [50 ng/mL]) into Col10. Pulp-dentin regeneration was evaluated by histological and immunofluorescence staining. Data were analyzed using 1-way or 2-way analysis of variance accordingly (α = 0.05). Rheology and microscopy data revealed that Col10 had a stiffness of 8,142 Pa with a more condensed and less porous structure, whereas Col3 had a stiffness of 735 Pa with a loose microstructure. Furthermore, both Col3 and Col10 supported DPSCs' survival. Quantitative polymerase chain reaction showed Col3 promoted significantly higher von Willebrand factor (VWF) and CD31 expression after 7 and 14 d under endothelial differentiation conditions (P < 0.05), whereas Col10 enhanced the expression of dentin sialophosphoprotein (DSPP), alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and collagen 1 (Col1) after 7, 14, and 21 d of odontogenic differentiation (P < 0.05). Hematoxylin and eosin and immunofluorescence (CD31 and vWF) staining revealed Col10+Col3+DPSCs+GFs enhanced pulp-dentin tissue regeneration. In conclusion, the collagen-based concentric construct modified by growth factors guided the specific lineage differentiation of DPSCs and promoted pulp-dentin tissue regeneration in vivo.

寻找一种合适的支架系统,以支持细胞的存活和功能,并最终支持牙髓-牙本质复合体的再生,仍然具有挑战性。在此,我们假设将牙髓干细胞(DPSCs)包裹在不同硬度的胶原蛋白水凝胶中,集中注射到牙片中,可再生出功能性牙髓和牙本质。制备了浓度为 3 毫克/毫升(Col3)和 10 毫克/毫升(Col10)的胶原水凝胶,并分别使用流变仪和扫描电子显微镜评估了它们的硬度和微观结构。然后将 DPSCs 包囊在水凝胶中,使用活/死检测法和定量实时聚合酶链反应评估它们的存活率以及向内皮细胞和牙本质细胞系分化的能力。在体内实验中,将含有或不含生长因子的不同硬度胶原水凝胶包裹的 DPSC 注入牙本质牙齿切片的牙髓腔,并植入严重联合免疫缺陷(SCID)小鼠的皮下。具体来说,在 Col3 中注入血管内皮生长因子(VEGF [50 ng/mL]),在 Col10 中注入骨形态发生蛋白(BMP2 [50 ng/mL])。通过组织学和免疫荧光染色对牙髓-牙本质再生进行评估。数据采用单因子或双因子方差分析(α = 0.05)进行分析。流变学和显微镜数据显示,Col10 的硬度为 8,142 Pa,结构更加凝结,孔隙较少;而 Col3 的硬度为 735 Pa,微观结构疏松。此外,Col3 和 Col10 都支持 DPSC 的存活。定量聚合酶链反应显示,在内皮分化条件下,Col3能在7天和14天后显著提高von Willebrand因子(VWF)和CD31的表达量(P < 0.05),而Col10则能在牙本质分化7天、14天和21天后提高牙本质磷蛋白(DSPP)、碱性磷酸酶(ALP)、runt相关转录因子2(Runx2)和胶原蛋白1(Col1)的表达量(P < 0.05)。血红素和伊红以及免疫荧光(CD31 和 vWF)染色显示 Col10+Col3+DPSCs+GFs 增强了牙髓-牙本质组织再生。总之,生长因子修饰的胶原同心构建物引导了 DPSCs 的特异性系分化,促进了体内牙髓-牙本质组织的再生。
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引用次数: 0
Salivary Glands and Viral Pathogenesis. 唾液腺与病毒发病机制
Pub Date : 2024-03-01 Epub Date: 2024-02-12 DOI: 10.1177/00220345231222871
N Atyeo, J O Maldonado, B M Warner, J A Chiorini

The oral cavity is an epidemiologically relevant route of viral transmission due to the shedding of viruses in saliva. With advancements in salivary diagnostics, an increasing number of viruses have been detected. However, the anatomic source of virus in saliva is still largely unknown. Some viruses have a well-established tropism for the salivary glands (SGs), and recent studies have emphasized the importance of the glands as potential reservoirs for infectious viruses. Viral infections of the SGs have been linked to acute and chronic SG pathology and may be associated with SG dysfunction, with phenotypes similar to those seen in SjÖgren's disease (SjD), an autoimmune condition that affects the salivary and lacrimal glands. Understanding the breadth of viruses that infect the SG and the conserved or distinct host responses to these infections may provide insights into the pathogenesis of virus-mediated SG diseases. There is a need for further research to fully understand the molecular mechanisms by which viruses enter and replicate in the glands, their physiologic impact on SG function, and whether the SGs can serve as a long-term reservoir for infectious viral particles. The purpose of this review is to highlight a group of viruses that infect the salivary gland: hepatitis C virus, hepatitis D virus, severe acute respiratory syndrome coronavirus 2, enteric viruses, human T-cell leukemia virus type I, human immunodeficiency virus, human cytomegalovirus, and BK polyomavirus. We focus on the effects of viral infection on salivary gland (SG) inflammation, function, and its association with SjD.

由于病毒会在唾液中脱落,因此口腔是一个与流行病学相关的病毒传播途径。随着唾液诊断技术的进步,越来越多的病毒被检测出来。然而,唾液中病毒的解剖学来源在很大程度上仍然是未知的。有些病毒对唾液腺(SG)有明显的滋养作用,最近的研究强调了唾液腺作为潜在的传染性病毒库的重要性。唾液腺的病毒感染与唾液腺的急性和慢性病变有关,并可能与唾液腺功能障碍有关,其表型与影响唾液腺和泪腺的自身免疫性疾病--斯约格伦病(SjÖgren's disease,SjD)相似。了解感染唾液腺的病毒的种类以及宿主对这些感染的反应是一致的还是不同的,有助于深入了解病毒介导的唾液腺疾病的发病机制。我们需要进一步研究,以充分了解病毒进入睑板腺并在睑板腺中复制的分子机制、病毒对睑板腺功能的生理影响以及睑板腺是否可作为传染性病毒颗粒的长期储存库。本综述的目的是重点介绍感染唾液腺的一组病毒:丙型肝炎病毒、丁型肝炎病毒、严重急性呼吸系统综合征冠状病毒 2、肠道病毒、人类 T 细胞白血病病毒 I 型、人类免疫缺陷病毒、人类巨细胞病毒和 BK 多瘤病毒。我们重点研究病毒感染对唾液腺(SG)炎症、功能的影响及其与 SjD 的关联。
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引用次数: 0
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Journal of dental research
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