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Multi-Omics Signatures of Periodontitis and Periodontal Therapy on the Oral and Gut Microbiome. 牙周炎和牙周治疗对口腔和肠道微生物组的多组学特征。
IF 3.4 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-27 DOI: 10.1111/jre.70055
Giacomo Baima, Shareef Dabdoub, Vivek Thumbigere-Math, Davide Giuseppe Ribaldone, Gian Paolo Caviglia, Leonardo Tenori, Linda Fantato, Alessia Vignoli, Mario Romandini, Ilario Ferrocino, Mario Aimetti

Aim: To characterize the impact of periodontitis and of Steps I-II of periodontal therapy on microbiome composition, function, and metabolic output across the oral and gut environments.

Methods: A multi-omics analysis was performed on saliva and stool samples collected from 50 systemically healthy individuals with and without Stage III-IV periodontitis. For participants with periodontitis, samples were analyzed both at baseline and 3 months after Steps I-II of periodontal therapy. High-throughput whole metagenome sequencing was used to profile microbial taxa and functional genes, NMR-based metabolomics profiled host-microbial metabolites. Single-omic differential abundance analysis between healthy samples and periodontitis samples was performed with MaAsLin2, while analysis between pre- and post-treatment was conducted with timeOmics. Variable selection and subsequent supervised multivariate analysis to determine group-separating markers utilized multi-level sparse Partial Least Squares Discriminant Analysis (sPLS-DA) through mixOmics. KEGG pathway enrichment was analyzed using clusterProfiler, whereas multi-omic data integration was performed with multi-block Partial Least Squares regression analysis.

Results: Periodontitis was associated with significant compositional and functional changes in both saliva and stool, with increased abundance of pathobionts and loss of health-associated taxa in both niches. A subset of species was shared across oral and gut habitats, with detectable differences across clinical groups. As functional potential, periodontitis enriched microbial pro-inflammatory pathways (lipopolysaccharide biosynthesis, bacterial motility) and depleted beneficial short-chain fatty acid (SCFA)- and vitamin-producing functions. Metabolomic profiles revealed reduced SCFAs and amino acids in periodontitis, with elevated pro-inflammatory metabolites (succinate, trimethylamine) in both saliva and stool. Following therapy, microbial communities and their metabolic output partially reverted toward health-associated profiles, particularly in saliva. Stool samples showed subtler but consistent shifts, including a decrease in some typically oral species and decreased succinate and methylamine and restoration of amino acid and SCFA-related metabolites.

Conclusions: Periodontitis is associated with coordinated microbial and metabolic signatures across the oral and gut environments. Non-surgical periodontal therapy promotes partial ecological restoration in both niches, supporting the view of oral health as a modifiable target for influencing systemic microbial homeostasis.

Trial registration: ClinicalTrials.gov identification number: NCT04826926.

目的:描述牙周炎和牙周治疗步骤I-II对口腔和肠道环境中微生物组组成、功能和代谢输出的影响。方法:对50名患有或不患有III-IV期牙周炎的全身健康个体的唾液和粪便样本进行多组学分析。对于患有牙周炎的参与者,在基线和牙周治疗步骤I-II后3个月对样本进行分析。利用高通量全宏基因组测序分析微生物分类群和功能基因,利用核磁共振代谢组学分析宿主微生物代谢物。使用MaAsLin2对健康样本和牙周炎样本进行单组学差异丰度分析,使用timeOmics对治疗前后样本进行分析。变量选择和随后的监督多变量分析利用mixOmics的多级稀疏偏最小二乘判别分析(sPLS-DA)来确定组分离标记。使用clusterProfiler分析KEGG通路富集,使用多块偏最小二乘回归分析进行多组数据整合。结果:牙周炎与唾液和粪便的显著组成和功能变化有关,在这两个生态位中,病原体的丰度增加,与健康相关的分类群的丧失。一部分物种在口腔和肠道栖息地共享,在临床组之间存在可检测到的差异。作为功能潜力,牙周炎丰富了微生物促炎途径(脂多糖生物合成,细菌运动),并耗尽了有益的短链脂肪酸(SCFA)和维生素生产功能。代谢组学分析显示牙周炎患者的SCFAs和氨基酸减少,唾液和粪便中的促炎代谢物(琥珀酸盐、三甲胺)升高。治疗后,微生物群落及其代谢输出部分恢复到与健康相关的特征,尤其是唾液。粪便样本显示出微妙但一致的变化,包括一些典型的口服物种减少,琥珀酸和甲胺减少,氨基酸和scfa相关代谢物恢复。结论:牙周炎与口腔和肠道环境中协调的微生物和代谢特征有关。非手术牙周治疗促进了这两个生态位的部分生态恢复,支持了口腔健康作为影响系统微生物稳态的可改变目标的观点。试验注册:ClinicalTrials.gov识别号:NCT04826926。
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引用次数: 0
Impact of Tooth Preservation or Replacement on Diet Quality: Modified Treatment Policies Approach. 牙齿保留或替换对饮食质量的影响:改良的治疗政策方法。
IF 3.4 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-27 DOI: 10.1111/jre.70053
John Rong Hao Tay, Ashish C Kalhan, Upul Cooray, Gustavo G Nascimento

Aim: To examine the impact of emulated natural tooth preservation or dental rehabilitation scenarios on diet quality among older adults in the United States, assessing what diet quality would be if people's dentition or rehabilitation status were improved.

Methods: Data from 2606 participants aged ≥ 60 across four NHANES cycles (2011-2018) were analyzed. Dentition status and prosthetic rehabilitation were clinically assessed, and diet quality was measured using the Healthy Eating Index (HEI)-2020. The modified treatment policies (MTP) framework was used to emulate hypothetical interventions of retaining natural teeth or providing prosthetic rehabilitation. Odds ratios (OR) for achieving better diet quality under each scenario were estimated using doubly robust targeted maximum likelihood estimation (TMLE).

Results: If all participants retained ≥ 25 teeth, the likelihood of achieving better HEI scores increased by 51% (OR = 1.51, 95% CI: 1.32-1.69). In a pragmatic scenario where each dentition group was shifted up by one level (edentulous → 1-9 teeth, 1-9 teeth → 10-19 teeth, 10-19 teeth → 20-25 teeth, 1-9 teeth → ≥ 25 teeth), the population had a 20% higher likelihood of achieving better diet quality (OR = 1.22, 95% CI: 1.14-1.29). Prosthetic rehabilitation yielded comparatively smaller effects, with rehabilitation in individuals with < 25 teeth improving the likelihood of better diet quality by 8% (OR = 1.08, 95% CI: 1.03-1.12).

Conclusion: The present observational study suggests that preserving natural teeth has a stronger population-level impact on diet quality than prosthetic rehabilitation replacing missing teeth in older adults.

目的:研究模拟天然牙齿保存或牙齿康复场景对美国老年人饮食质量的影响,评估如果人们的牙齿或康复状态得到改善,饮食质量会如何。方法:分析四个NHANES周期(2011-2018)中2606名年龄≥60岁的参与者的数据。临床评估牙列状态和假肢康复,并使用健康饮食指数(HEI)-2020测量饮食质量。修改后的治疗政策(MTP)框架被用来模拟保留天然牙齿或提供假体康复的假设干预措施。使用双稳健目标最大似然估计(TMLE)估计每种情况下获得更好饮食质量的比值比(OR)。结果:如果所有参与者保留≥25颗牙齿,获得更好的HEI评分的可能性增加51% (OR = 1.51, 95% CI: 1.32-1.69)。在实用场景中,每个牙列组向上移动一个水平(无牙→1-9颗牙,1-9颗牙→10-19颗牙,10-19颗牙→20-25颗牙,1-9颗牙→≥25颗牙),人群获得更好饮食质量的可能性高出20% (OR = 1.22, 95% CI: 1.14-1.29)。结论:目前的观察性研究表明,在老年人中,保留天然牙齿对饮食质量的影响比修复修复替代缺失牙齿对饮食质量的影响更大。
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引用次数: 0
Air-Polishing Versus Ultrasonic Instrumentation for Nonsurgical Treatment of Peri-Implantitis: A Randomized Clinical Trial. 空气抛光与超声仪器非手术治疗种植体周围炎:一项随机临床试验。
IF 3.4 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-18 DOI: 10.1111/jre.70054
Ana Isabel Moreira, Tiago Caetano, Francisco Correia, Honorato Ribeiro-Vidal, Ricardo Faria Almeida

This RCT offers a nuanced understanding of nonsurgical peri-implantitis management (air polishing with erythritol versus ultrasonic instrumentation, in combination with systemic metronidazole), integrating both clinical and patient-centered outcomes. The results showed that the ultrasonic instrumentation reduced probing depth and bleeding on probing, throughout the 12-month period.

该随机对照试验对非手术治疗种植体周围炎(赤藓糖醇空气抛光与超声仪器联合全身甲硝唑)提供了细致入微的理解,整合了临床和以患者为中心的结果。结果显示,在12个月的时间里,超声仪器减少了探探深度和探探出血。
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引用次数: 0
Periodontal Medicine: The Past, the Present, the Future 牙周医学:过去,现在,未来。
IF 3.4 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-15 DOI: 10.1111/jre.70052
Bruno G. Loos, Magda Feres
<p>The introduction and recognition of the domain of “Periodontal Medicine” can be regarded as one of the greatest paradigm shifts in the realm of periodontology. The explosion of journal articles in the last four decades on the links between periodontitis, systemic diseases, systemic consequences and related pathophysiological pathways, is overwhelming to date. Also, the number of scientific articles on periodontal medicine related subjects published in medical and non-dental journals has increased importantly in the same period. We have come to the point that the traditional separation between medicine and dentistry is fading where the obvious interrelationship between mouth and body is gaining momentum beyond doubt. We can consider periodontitis now a medical condition in its own right [<span>1</span>]. At the occasion of the 60th anniversary of the Journal of Periodontal Research, we present here a short perspective on the past, the present, the future of periodontal medicine.</p><p>At the beginning of the 20th century, the doctrine of ‘focal infection’ promoted the belief that oral infections were the root cause of many systemic diseases, to the extent that extracting all teeth was often recommended as a preventive measure [<span>2, 3</span>]. In the decades that followed, this concept was largely abandoned, and oral diseases came to be regarded as disconnected from the rest of the body. It was not until the 1980s and 1990s, that this assumption of disconnection was convincingly refuted. In short, the scientific evolution of understanding much better biological and pathophysiological concepts, the understanding that all organs and bodily tissues are interconnected, as well as clearly common sense, made the focal infection theory untenable. The scientific world began to rely to a much larger extent on modern evidence-based frameworks rather than observational research. Biostatistics became an important scientific aspect in our scientific publications. The fields of epidemiology, microbiology, immunology and the understanding of systemic inflammation (e.g., in atherosclerotic cardiovascular diseases [ACVD]), underwent methodological revolutions that enabled the redefinition of the field. Thus first, several European studies demonstrated that periodontitis and poor oral health could be associated with ACVD [<span>4, 5</span>]. In 1996, Steven Offenbacher introduced the term “periodontal medicine” [<span>6</span>], signifying the need to view the mouth as an integral part of systemic health. Offenbacher and colleagues suggested that periodontitis should be considered alongside other major noncommunicable diseases such as diabetes mellitus, rheumatoid arthritis, Crohn's disease and ACVD. A well-remembered symposium in 1997 in Chapel Hill, North Carolina, USA, further consolidated the concept of periodontal medicine. It provided greater clarity on the associations between periodontitis and multiple systemic conditions, including diabetes mellitus
例如,在结直肠癌和炎症性肠病患者中发现了超过55000个口腔易位基因,为口腔病原体转移到肠道提供了遗传证据[15,16]。此外,实验动物研究表明,牙周组织炎症对中性粒细胞动员和启动[17]具有全身性影响;观察结扎性牙周病小鼠骨髓中性粒细胞计数升高。此外,在患有诱发性牙龈炎症的人类志愿者中,由于炎症“溢出”到循环中,在体外刺激下发现血液中性粒细胞的激活显著增加。此外,在人类中,多篇论文表明牙周治疗与典型系统性炎症生物标志物IL-6和CRP水平降低有关[18-21]。另一个目前重要的机制是进一步了解牙周炎与某些全身性疾病之间已证实的关联,与骨髓生成不良和自身免疫反应的发展有关。因此,已经证实了牙周炎中的免疫细胞功能障碍[17,22]。除了这些分子途径之外,同样重要的是临床途径,即牙齿脱落本身会引起咀嚼功能障碍,导致不利的饮食和营养变化。例如,在系统评价的全面概述中,发现完全或部分缺牙的个体更容易营养不良或有营养不良的风险。最后,许多全身性疾病都有共同的潜在炎症机制,可能表现在多个器官中[24,25]。这一概念被描述为宿主免疫反应的多效性,根据年龄、基因、环境、生活方式和表观遗传变化之间的复杂相互作用,表现出不同的表现。除了这些机制的见解外,目前的证据越来越强调牙周炎是更广泛的多病模式的一部分。患有牙周炎的患者更有可能患有其他全身性疾病,并且共病和多病的患病率明显高于没有牙周炎的患者。此外,在多种疾病的牙周炎患者中,可能出现不同的发病率集群,其中一些患者属于心脏代谢集群,另一些患者属于(自身)免疫和呼吸系统疾病集群[26-29]。此外,我们现在认识到,牙周炎应该像许多其他慢性非传染性疾病一样被视为一种全身性疾病,它像许多其他非传染性疾病一样,影响个人的全身状况和健康。事实上,有效的牙周治疗已被证明可以增强糖尿病患者的代谢调节,并改善生化和临床心血管危险指标[31]。换句话说,口腔健康是整体健康的一个组成部分,一个未经治疗的严重牙周炎患者不能被认为是健康的,但它的治疗确实改善了整体健康。人工智能(AI)应用的快速增长正在深刻地重塑当今时代。用于数据分析和预测建模的大型语言模型(llm)和机器学习(ML)为未来开辟了全新的途径。例如,最近发表的一项重大进展表明,llm可以高精度地预测1000多种疾病的未来风险。这些模型在40万英国生物银行个人身上进行了训练,并在190万丹麦人身上进行了验证,使用的是电子健康记录和人口统计数据。类似地,尽管在更小的范围内,ML模型已经能够从非图像电子牙科记录[33]预测牙周炎的发作,并显示出直接从口内x线片[34]估计牙周稳定性的能力。此外,ML最近也被应用于通过整合临床和唾液生物标志物数据[35]来预测牙周炎的进展,并预测个体对牙周治疗的反应[36]。虽然在临床应用之前需要进行前瞻性验证,但这些模型代表了未来预测疾病发病,实现早期和简化诊断,改善疾病进展预测以及支持旨在提高患者预后的更个性化治疗计划的有希望的步骤。随着我们从现在走向未来,我们今天已经看到了人工智能的日益普及如何重塑了我们的世界。此外,科学界和医学界正在接受人工智能的巨大潜力。然而,预测“后天”仍然是一个重大挑战。 考虑到这一局限性,我们仍然可以推测,一个现实的情况是逐步采用整体方法,或“精确牙周医学”,作为牙科实践的主流范例。首先,这种模式可能会在牙周专科实践中被采用,在那里综合治疗整合了系统风险评估。例如,通过几个关键问题和使用一滴血或唾液的快速椅边测试,可能很快就能估计出患者的心脏代谢风险。结合人工智能驱动的算法,这些工具将产生个性化的风险概率,使牙科专业人员能够更好地定制治疗方案,提供更好的生活方式指导,此外,还可以决定何时咨询医生。相反,医学专业人员将更好地意识到牙周炎是一种合并症,并且越来越多地认识到未经治疗的牙周炎会损害他们自己专业的结果。提高对牙周炎与其他慢性疾病的认识,可能有助于打破医学和牙科专业人员之间长期存在的障碍。我们可以设想,医学专家使用人工智能工具来筛查患者的牙周炎和其他相关疾病,从而促进真正的跨学科护理。在促进更健康的生活方式、改善饮食习惯或管理全身药物和疗法的不良口服副作用方面,合作倡议也将变得越来越重要。此外,可穿戴技术可能会进一步加速牙周医学在日常生活中的整合,提供诸如生活习惯指导、正确刷牙和牙间清洁等功能,以及监测血糖和全身炎症水平。因此,随着这些发展,我们的研究重点可能会转向“大数据”调查,我们将与科技公司(包括电动牙刷制造商)合作,并将重点放在改善生活习惯的方法上,从正确刷牙到健康饮食再到智力锻炼。而且,为了揭示牙周炎中更多复杂的病理力学,如果雄心勃勃的研究人员在至少5-10年的时间里,在国际联盟中启动一个牙周数据库和生物库,利用基于实践的数据,从而包括数百万患者的所有特征,这将是一个开创性的努力。有了这些“真实世界数据”和人工智能的广泛应用,就可以推出真正个性化的牙周病医学。可以在护理点建立个人多因果模型,并制定个性化的预防和治疗计划。有了这个,牙科专业人员可以参与到每个牙周炎患者的整体健康方法中。然而,虽然精准牙周医学的重点是通过考虑每个患者独特的遗传、生物和环境因素来提供个性化的治疗,但需要考虑的是,这种方法需要一个更加综合的医疗保健系统,该系统将口腔健康视为整体健康的重要组成部分,并促进医学和牙科专业人员之间的合作。同时,精密牙周医学可能有各种含义。首先,这涉及伦理问题,例如通过个性化健康信息确保患者隐私和数据安全,认识到在获得先进诊断和治疗方式方面的差异,以及在将复杂的个人和生物数据纳入护理模式时可能的知情同意。另一个含义是“教育”;目前的牙科和医学院课程需要包含口腔健康和一般健康之间系统联系的知识,需要促进跨学科培训以促进牙科和医疗从业人员之间的合作,并且必须教育患者和现有提供者了解综合护理的重要性。最后,在公共卫生一级,必须制定政策,承认并支持口腔和全身健康之间的联系(即牙周医学),以改善人口健康结果,包括实施同时处理口腔和全身疾病的预防战略。在公共卫生专家的帮助下,需要向决策者提供充分的文件,证明通过强调早期发现和全面管理健康问题,并将偏离口腔健康作为早期预警信号,可以降低卫生保健成本。总之,随着今天的技术进步,未来可能会比我们预期的来得更快。这不仅标志着又向前迈进了一步,而且标志着新篇章的开启。 从早期的局灶性感染学说,经过口腔和身体之间长期脱节的时代,到牙周医学的诞生,我们现在接近牙科和医学学科的即将融合,标志着综合医疗保健的新时代。作者声明无利益冲突。数据共享不适用于本文,因为在当前研究期间没有生成或分析数据集。
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引用次数: 0
From Disease to Illness: Reframing Periodontitis Through an Anthropological Lens. 从疾病到疾病:从人类学的角度重新定义牙周炎。
IF 3.4 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-07 DOI: 10.1111/jre.70051
Carlo Galli, Chiara Moretti, Elena Calciolari, Nikolaos Donos

While periodontitis is globally recognized as a significant public health problem, its common definition as a plaque-based inflammatory condition is incomplete. Disease progression, personal experience, and treatment are shaped by social, economic, and structural forces largely invisible in clinical practice and policy. A lens from medical anthropology helps us see periodontitis as more than a clinical diagnosis; it is a lived experience, deeply entangled with a person's social world. The physical reality of inflammation translates into profound emotional distress-from the shame and stigma of bleeding gums and gingival recession to the tangible fear of tooth loss. This personal suffering is often intensified by a societal focus on individual blame, which masks systemic barriers like poor insurance coverage and the simple lack of local care. Ultimately, the cultural language and assumptions surrounding oral health-what anthropologists term explanatory models and semantic networks-powerfully influence everything from a patient's decisions to the public's perception of the disease itself. We argue for a more culturally attuned approach to periodontal health-one that prioritizes prevention, centers the patient's lived experience, and confronts the systemic roots of oral health inequities. By integrating the insights of anthropology with the science of periodontics, we believe we can build a more complete model of care that leads to equitable health outcomes, creating policies and practices that acknowledge both microbial causes and patients' lived realities.

虽然牙周炎是全球公认的重大公共卫生问题,但其作为菌斑基础炎症的共同定义是不完整的。疾病进展、个人经历和治疗受到社会、经济和结构性力量的影响,这些力量在临床实践和政策中基本上是看不见的。从医学人类学的角度来看,牙周炎不仅仅是一种临床诊断;它是一种活生生的经历,与一个人的社会世界深深纠缠在一起。炎症的物理现实转化为深刻的情感痛苦——从牙龈出血和牙龈萎缩的羞耻和耻辱到牙齿脱落的切实恐惧。社会对个人责任的关注往往加剧了这种个人痛苦,这掩盖了诸如保险覆盖面差和缺乏当地护理等系统性障碍。最终,围绕口腔健康的文化语言和假设——人类学家称之为解释模型和语义网络——有力地影响着从病人的决定到公众对疾病本身的看法的一切。我们主张一种更符合文化的牙周健康方法——优先考虑预防,以患者的生活经验为中心,并面对口腔健康不平等的系统性根源。通过将人类学的见解与牙周病科学相结合,我们相信我们可以建立一个更完整的护理模型,从而带来公平的健康结果,制定既承认微生物原因又承认患者生活现实的政策和实践。
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引用次数: 0
Tartrate-Resistant Acid Phosphatase-Positive Cells: Putative Mediators of Peri-Implant Bone Healing. 抗酒石酸酸性磷酸酶阳性细胞:种植体周围骨愈合的假定介质。
IF 3.4 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-01 Epub Date: 2025-07-19 DOI: 10.1111/jre.70019
Nahrain Warda, Ryan Noh, J E Davies

A pre-clinical rabbit study shows peri-implant tissue contains mono- and multinucleate tartrate-resistant acid phosphatase (TRAP) + cells and a plethora of punctate extracellular TRAP staining. The latter provides a putative extracellular vesicular trafficking mechanism by which these cells drive early osseointegration.

一项兔临床前研究显示,种植体周围组织含有单核和多核酒石酸抗性酸性磷酸酶(TRAP) +细胞和大量点状细胞外TRAP染色。后者提供了一种假定的细胞外囊泡运输机制,这些细胞通过该机制驱动早期骨整合。
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引用次数: 0
Porphyromonas gingivalis-Lipopolysaccharide Induced Gingival Fibroblasts Trained Immunity Sustains Inflammation in Periodontitis. 牙龈卟啉单胞菌-脂多糖诱导的牙龈成纤维细胞训练免疫维持牙周炎的炎症。
IF 3.4 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-01 Epub Date: 2024-12-12 DOI: 10.1111/jre.13372
Jiayi Liu, Haoyang Tian, Jinhong Ju, Fujiao Nie, Qiuyue Yin, Jingjing Zhao, Suli Wang, Hongmei Guo, Pishan Yang

Aim: To investigate whether trained immunity occurs in gingival fibroblasts (GFs) and its relationship to the persistence of inflammation in periodontitis.

Methods: Periodontally healthy and inflammatory gingival fibroblasts (HGFs and IGFs) were cultured through continuous adherence subculture of tissue blocks. Trained immunity in HGFs was evaluated via a classic in vitro model, with relevant markers assessed via enzyme-linked immunosorbent assay, lactate content assay, glycolytic rate assay, and chromatin immunoprecipitation. A histone methyltransferase blocker and a PI3K inhibitor were added to investigate the mechanisms underlying trained immunity. The relationship between trained immunity and periodontitis was further examined via immunofluorescence staining and chromatin immunoprecipitation on IGFs.

Results: Compared with untrained cells, GFs trained with Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS) exhibited a significant increase in IL-6 and TNF-α secretion, enhanced glycolytic metabolism, and enriched mono-methylation of lysine 4 on histone H3 (H3K4me1) at the enhancer regions of TNF-α and IL-6. The addition of a histone methyltransferase blocker and a PI3K inhibitor greatly reduced trained immunity. Additionally, the response of IGFs to P. gingivalis-LPS stimulation and their epigenetic modifications were similar to those observed in trained HGFs.

Conclusion: This study novelly discovered that both P. gingivalis-LPS-stimulated HGFs and IGFs in periodontitis acquired trained immunity. Following P. gingivalis-LPS stimulation, HGFs underwent metabolic and epigenetic changes via the PI3K/AKT pathway, with these epigenetic changes also observed in IGFs. This finding suggests that trained immunity in GFs may be a key mechanism underlying the recurrence and persistence of periodontitis.

目的:探讨牙周炎患者牙龈成纤维细胞(GFs)是否存在训练免疫及其与炎症持续的关系。方法:采用组织块连续贴壁传代法培养牙周健康牙龈成纤维细胞(HGFs)和炎性牙龈成纤维细胞(IGFs)。通过经典的体外模型评估hgf的训练免疫,并通过酶联免疫吸附法、乳酸含量法、糖酵解率法和染色质免疫沉淀法评估相关标志物。加入组蛋白甲基转移酶阻断剂和PI3K抑制剂来研究训练免疫的机制。通过免疫荧光染色和IGFs的染色质免疫沉淀进一步研究免疫训练与牙周炎的关系。结果:与未培养的细胞相比,经牙龈卟啉单胞菌-脂多糖(P. gingivalis-LPS)培养的GFs显示出IL-6和TNF-α分泌显著增加,糖酵解代谢增强,TNF-α和IL-6增强区组蛋白H3 (H3K4me1)上赖氨酸4的单甲基化富集。组蛋白甲基转移酶阻滞剂和PI3K抑制剂的加入大大降低了训练后的免疫力。此外,IGFs对P. gingivalis-LPS刺激的反应及其表观遗传修饰与训练后的hgf相似。结论:本研究新颖地发现牙龈假单胞菌多糖刺激的HGFs和IGFs在牙周炎中获得了训练免疫。在P. gingivalis-LPS刺激下,hgf通过PI3K/AKT通路发生代谢和表观遗传变化,这些表观遗传变化也在IGFs中观察到。这一发现表明,GFs的免疫训练可能是牙周炎复发和持续的关键机制。
{"title":"Porphyromonas gingivalis-Lipopolysaccharide Induced Gingival Fibroblasts Trained Immunity Sustains Inflammation in Periodontitis.","authors":"Jiayi Liu, Haoyang Tian, Jinhong Ju, Fujiao Nie, Qiuyue Yin, Jingjing Zhao, Suli Wang, Hongmei Guo, Pishan Yang","doi":"10.1111/jre.13372","DOIUrl":"10.1111/jre.13372","url":null,"abstract":"<p><strong>Aim: </strong>To investigate whether trained immunity occurs in gingival fibroblasts (GFs) and its relationship to the persistence of inflammation in periodontitis.</p><p><strong>Methods: </strong>Periodontally healthy and inflammatory gingival fibroblasts (HGFs and IGFs) were cultured through continuous adherence subculture of tissue blocks. Trained immunity in HGFs was evaluated via a classic in vitro model, with relevant markers assessed via enzyme-linked immunosorbent assay, lactate content assay, glycolytic rate assay, and chromatin immunoprecipitation. A histone methyltransferase blocker and a PI3K inhibitor were added to investigate the mechanisms underlying trained immunity. The relationship between trained immunity and periodontitis was further examined via immunofluorescence staining and chromatin immunoprecipitation on IGFs.</p><p><strong>Results: </strong>Compared with untrained cells, GFs trained with Porphyromonas gingivalis-lipopolysaccharide (P. gingivalis-LPS) exhibited a significant increase in IL-6 and TNF-α secretion, enhanced glycolytic metabolism, and enriched mono-methylation of lysine 4 on histone H3 (H3K4me1) at the enhancer regions of TNF-α and IL-6. The addition of a histone methyltransferase blocker and a PI3K inhibitor greatly reduced trained immunity. Additionally, the response of IGFs to P. gingivalis-LPS stimulation and their epigenetic modifications were similar to those observed in trained HGFs.</p><p><strong>Conclusion: </strong>This study novelly discovered that both P. gingivalis-LPS-stimulated HGFs and IGFs in periodontitis acquired trained immunity. Following P. gingivalis-LPS stimulation, HGFs underwent metabolic and epigenetic changes via the PI3K/AKT pathway, with these epigenetic changes also observed in IGFs. This finding suggests that trained immunity in GFs may be a key mechanism underlying the recurrence and persistence of periodontitis.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":"1156-1167"},"PeriodicalIF":3.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exosomal miR-155-5p Facilitates Lipopolysaccharide Transport and Foam Cell Formation: A Novel Link Between Periodontitis and Atherosclerosis. 外泌体 miR-155-5p 促进脂多糖运输和泡沫细胞形成:牙周炎与动脉粥样硬化之间的新联系
IF 3.4 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-01 Epub Date: 2024-11-27 DOI: 10.1111/jre.13369
Wen-Wen Yang, Qing-Xiang Li, Fei Wang, Xin-Ran Zhang, Xian-Li Zhang, Meng Wang, Dong Xue, Ying Zhao, Lu Tang

Aim: To investigate the role of lipopolysaccharide (LPS) from Porphyromonas gingivalis and miR-155-5p-enriched exosomes in the formation of foam cells and the occurrence of carotid atherosclerosis (CAS).

Methods: The CAS tissue samples and plasma from the healthy control group or patients undergoing periodontitis without CAS and with CAS were collected at the Xuanwu Hospital, Capital Medical University. The expression level of miR-155-5p was evaluated by immunofluorescent analysis and qRT-PCR. Oil red O staining and lipid accumulation assays were performed to explore the effects of LPS and miR-155-5p on mouse macrophage Raw264.7 and human monocytes THP-1. The expression levels of lipid-regulated genes were detected by qRT-PCR. Dual-luciferase reporter gene assay and DET1 overexpressed or inhibited Raw264.7 cells were used to verify the target gene of exosomal miR-155-5p. ApoE-/- mice were used to confirm the auxo-action of atherosclerosis from exosomal miR-155-5p in vivo, and LAL assay was used to detect the LPS content.

Results: miR-155-5p was higher in patients with periodontitis and CAS plasma exosomes than those in patients without CAS. The expression of miR-155-5p was significantly increased in CAS tissues compared with Normal tissues, and the expression level of miR-155-5p was associated with lipid-regulated genes in CAS tissues. MiR-155-5p-enriched exosomes accelerated lipid accumulation in macrophage-like cells and promoted the activity of lipid-accumulation genes by targeting DET1. In ApoE-/- mice, circulating miR-155-5p-enriched exosomes captured LPS, and the LPS-laden exosomes conferred plasma access for LPS, triggering the formation of foam cells and the occurrence of CAS.

Conclusion: miR-155-5p enriched exosomes capture and escort LPS to the atherosclerotic sites, licensing the formation of foam cells and thus promoting CAS.

目的:研究牙龈卟啉单胞菌脂多糖(LPS)和富含miR-155-5p的外泌体在泡沫细胞形成和颈动脉粥样硬化(CAS)发生中的作用:方法:在首都医科大学宣武医院采集健康对照组或无CAS和有CAS的牙周炎患者的CAS组织样本和血浆。通过免疫荧光分析和 qRT-PCR 检测 miR-155-5p 的表达水平。为了探讨 LPS 和 miR-155-5p 对小鼠巨噬细胞 Raw264.7 和人单核细胞 THP-1 的影响,进行了油红 O 染色和脂质积累实验。通过 qRT-PCR 检测脂质调控基因的表达水平。双荧光素酶报告基因检测和 DET1 过表达或抑制 Raw264.7 细胞用于验证外泌体 miR-155-5p 的靶基因。结果:miR-155-5p在牙周炎患者和CAS血浆外泌体中的表达高于未患CAS的患者。与正常组织相比,miR-155-5p在CAS组织中的表达明显升高,且miR-155-5p的表达水平与CAS组织中的脂质调控基因相关。富集的miR-155-5p外泌体通过靶向DET1加速了巨噬细胞样细胞的脂质积累,并促进了脂质积累基因的活性。在载脂蛋白E-/-小鼠中,循环中富含miR-155-5p的外泌体捕获了LPS,而负载LPS的外泌体使LPS进入血浆,引发了泡沫细胞的形成和CAS的发生。
{"title":"Exosomal miR-155-5p Facilitates Lipopolysaccharide Transport and Foam Cell Formation: A Novel Link Between Periodontitis and Atherosclerosis.","authors":"Wen-Wen Yang, Qing-Xiang Li, Fei Wang, Xin-Ran Zhang, Xian-Li Zhang, Meng Wang, Dong Xue, Ying Zhao, Lu Tang","doi":"10.1111/jre.13369","DOIUrl":"10.1111/jre.13369","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the role of lipopolysaccharide (LPS) from Porphyromonas gingivalis and miR-155-5p-enriched exosomes in the formation of foam cells and the occurrence of carotid atherosclerosis (CAS).</p><p><strong>Methods: </strong>The CAS tissue samples and plasma from the healthy control group or patients undergoing periodontitis without CAS and with CAS were collected at the Xuanwu Hospital, Capital Medical University. The expression level of miR-155-5p was evaluated by immunofluorescent analysis and qRT-PCR. Oil red O staining and lipid accumulation assays were performed to explore the effects of LPS and miR-155-5p on mouse macrophage Raw264.7 and human monocytes THP-1. The expression levels of lipid-regulated genes were detected by qRT-PCR. Dual-luciferase reporter gene assay and DET1 overexpressed or inhibited Raw264.7 cells were used to verify the target gene of exosomal miR-155-5p. ApoE<sup>-/-</sup> mice were used to confirm the auxo-action of atherosclerosis from exosomal miR-155-5p in vivo, and LAL assay was used to detect the LPS content.</p><p><strong>Results: </strong>miR-155-5p was higher in patients with periodontitis and CAS plasma exosomes than those in patients without CAS. The expression of miR-155-5p was significantly increased in CAS tissues compared with Normal tissues, and the expression level of miR-155-5p was associated with lipid-regulated genes in CAS tissues. MiR-155-5p-enriched exosomes accelerated lipid accumulation in macrophage-like cells and promoted the activity of lipid-accumulation genes by targeting DET1. In ApoE<sup>-/-</sup> mice, circulating miR-155-5p-enriched exosomes captured LPS, and the LPS-laden exosomes conferred plasma access for LPS, triggering the formation of foam cells and the occurrence of CAS.</p><p><strong>Conclusion: </strong>miR-155-5p enriched exosomes capture and escort LPS to the atherosclerotic sites, licensing the formation of foam cells and thus promoting CAS.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":"1132-1142"},"PeriodicalIF":3.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Does Computer-Assisted Surgery Improve the Accuracy of Immediate Implant Placement? A Systematic Review and Network Meta-Analysis. 计算机辅助手术能提高即刻种植体放置的准确性吗?系统回顾与网络元分析。
IF 3.4 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-01 Epub Date: 2025-07-10 DOI: 10.1111/jre.70010
Lucia Schiavon, Leonardo Mancini, Eugenia Settecase, Ronald E Jung, Tim Joda

Aim: This systematic review and network meta-analysis aimed to answer the PICO question: In patients undergoing immediate implant placement (IIP) [P], does Computer-Assisted Implant Surgery (CAIS) [I] lead to higher accuracy [O] compared to free-hand (FH) [C] implant placement?

Methods: A systematic search of MEDLINE, Scopus, and Cochrane databases was conducted for randomized clinical trials (RCTs) published between January 2014 and September 2024, comparing accuracy of CAIS and FH for IIP. Two reviewers screened the studies and extracted data for a network meta-analysis.

Results: Of 2064 records screened, 7 RCTs (338 implants and 291 patients) met the inclusion criteria. These RCTs evaluated FH and dynamic, full static, and partial static CAIS for single or partial implant placement. No RCTs analyzing robotic-assisted implant surgery (RAIS) were found. In 71.4% of the studies, IIP was performed in the anterior maxilla using a flapless approach. Accuracy was assessed by angular, cervical, and apical deviations between planned and real implant positions. All CAIS methods demonstrated significantly higher accuracy than FH (p < 0.05), but no significant differences were observed between CAIS approaches.

Conclusions: CAIS significantly improves IIP accuracy, enhancing 3D implant positioning and prosthetic outcomes. All CAIS techniques revealed comparable accuracy, allowing clinicians to select the most suitable approach for each patient.

Trial registration: PROSPERO identification number: CRD42024554241.

目的:本系统综述和网络荟萃分析旨在回答PICO问题:在接受即时种植体置入术(IIP) [P]的患者中,计算机辅助种植体手术(CAIS) [I]是否比徒手种植体置入术(FH) [C]具有更高的准确性[O] ?方法:系统检索MEDLINE、Scopus和Cochrane数据库中2014年1月至2024年9月发表的随机临床试验(RCTs),比较CAIS和FH诊断IIP的准确性。两名审稿人筛选研究并提取数据进行网络荟萃分析。结果:在筛选的2064条记录中,有7项rct(338个种植体和291例患者)符合纳入标准。这些随机对照试验评估了FH和动态、全静态和部分静态CAIS用于单个或部分种植体放置。没有发现分析机器人辅助种植手术(RAIS)的随机对照试验。在71.4%的研究中,采用无瓣入路在前上颌进行IIP。通过计划种植体和真实种植体位置之间的角度、颈椎和根尖偏差来评估准确性。结论:CAIS可显著提高IIP精度,增强3D种植体定位和修复效果。所有CAIS技术显示出相当的准确性,允许临床医生为每个患者选择最合适的方法。试验注册:普洛斯彼罗识别号:CRD42024554241。
{"title":"Does Computer-Assisted Surgery Improve the Accuracy of Immediate Implant Placement? A Systematic Review and Network Meta-Analysis.","authors":"Lucia Schiavon, Leonardo Mancini, Eugenia Settecase, Ronald E Jung, Tim Joda","doi":"10.1111/jre.70010","DOIUrl":"10.1111/jre.70010","url":null,"abstract":"<p><strong>Aim: </strong>This systematic review and network meta-analysis aimed to answer the PICO question: In patients undergoing immediate implant placement (IIP) [P], does Computer-Assisted Implant Surgery (CAIS) [I] lead to higher accuracy [O] compared to free-hand (FH) [C] implant placement?</p><p><strong>Methods: </strong>A systematic search of MEDLINE, Scopus, and Cochrane databases was conducted for randomized clinical trials (RCTs) published between January 2014 and September 2024, comparing accuracy of CAIS and FH for IIP. Two reviewers screened the studies and extracted data for a network meta-analysis.</p><p><strong>Results: </strong>Of 2064 records screened, 7 RCTs (338 implants and 291 patients) met the inclusion criteria. These RCTs evaluated FH and dynamic, full static, and partial static CAIS for single or partial implant placement. No RCTs analyzing robotic-assisted implant surgery (RAIS) were found. In 71.4% of the studies, IIP was performed in the anterior maxilla using a flapless approach. Accuracy was assessed by angular, cervical, and apical deviations between planned and real implant positions. All CAIS methods demonstrated significantly higher accuracy than FH (p < 0.05), but no significant differences were observed between CAIS approaches.</p><p><strong>Conclusions: </strong>CAIS significantly improves IIP accuracy, enhancing 3D implant positioning and prosthetic outcomes. All CAIS techniques revealed comparable accuracy, allowing clinicians to select the most suitable approach for each patient.</p><p><strong>Trial registration: </strong>PROSPERO identification number: CRD42024554241.</p>","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":"1067-1085"},"PeriodicalIF":3.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12779184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Peri-Implant Diseases: The Past, the Present, the Future. 种植体周围疾病:过去,现在,未来。
IF 3.4 3区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-11-01 Epub Date: 2025-12-22 DOI: 10.1111/jre.70061
Tord Berglundh
{"title":"Peri-Implant Diseases: The Past, the Present, the Future.","authors":"Tord Berglundh","doi":"10.1111/jre.70061","DOIUrl":"10.1111/jre.70061","url":null,"abstract":"","PeriodicalId":16715,"journal":{"name":"Journal of periodontal research","volume":" ","pages":"1059-1066"},"PeriodicalIF":3.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12779196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of periodontal research
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