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Histochemical assessment of the anabolic effects of abaloparatide on the femoral metaphyses of ovariectomized mice 去卵巢小鼠股骨干合成代谢作用的组织化学评价
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-06-01 Epub Date: 2025-04-18 DOI: 10.1016/j.job.2025.100663
Xuanyu Liu , Tomoka Hasegawa , Mako Sakakibara , Tomomaya Yamamoto , Mai Haraguchi-Kitakamae , Hotaka Ishizu , Yan Shi , Jiaxin Cui , Weisong Li , Wang Haoyu , Hiromi Hongo , Tomohiro Shimizu , Yoichi Ohiro , Norio Amizuka

Objective

To clarify the mechanism of bone anabolism induced by the parathyroid hormone-related peptide analog abaloparatide, we histochemically examined the femora of ovariectomized mice treated with abaloparatide.

Methods

Twelve-week-old female C57BL/6J mice underwent ovariectomies (OVX), and were then administered either abaloparatide (30 μg/kg/day: OVX + ABL group) or vehicle (OVX group) via daily intraperitoneal injection. Femora were harvested at 0, 2, 4, and 6 weeks post-administration and subjected to micro-CT imaging, TRAP, cathepsin K, ALP, and PHOSPHO1 staining, along with calcein labeling.

Results

In the OVX group, trabecular number and bone volume gradually decreased over time, whereas the OVX + ABL group maintained these values to 6 weeks after OVX. The numbers of TRAP-positive/cathepsin K-reactive osteoclasts per bone surface area were similar between the OVX and OVX + ABL group, except for a temporary increase at 4 weeks in the OVX group. In the OVX group, the areas of ALP-positive osteoblastic cells and PHOSPHO1-reactive mature osteoblasts decreased, whereas in the OVX + ABL group, ALP-positive osteoblastic cells surrounded the trabeculae, and long lines of PHOSPHO1-reactive mature osteoblasts expanded to the terminal region of the trabeculae. In addition, long continuous calcein labeling was seen on slightly convex new bone, indicating modeling-based bone formation in the OVX + ABL group. The bone formation rate/bone surface ratio and the total length of modeling-based bone formation sites were higher in the OVX + ABL group than in the OVX group.

Conclusion

Abaloparatide suppresses bone loss following ovariectomy by promoting both remodeling-based and modeling-based bone formation.
目的通过对去卵巢小鼠的股骨进行组织化学检测,探讨甲状旁腺激素相关肽类似物阿巴巴拉肽诱导骨合成代谢的机制。方法12周龄雌性C57BL/6J小鼠经卵巢切除术(OVX)后,每天腹腔注射阿巴巴拉肽(30 μg/kg/d: OVX + ABL组)或对照物(OVX组)。在给药后0、2、4和6周采集股骨,进行显微ct成像、TRAP、组织蛋白酶K、ALP和PHOSPHO1染色,并进行钙黄蛋白标记。结果OVX组骨小梁数和骨体积随时间逐渐减少,而OVX + ABL组在OVX后6周内保持不变。在OVX和OVX + ABL组之间,每个骨表面积的trap阳性/cathepsin k反应性破骨细胞的数量相似,除了OVX组在4周时暂时增加。OVX组中,alp阳性的成骨细胞和phospho1反应的成熟成骨细胞的面积减少,而OVX + ABL组中,alp阳性的成骨细胞包围小梁,并且长列的phospho1反应的成熟成骨细胞扩展到小梁末端区域。此外,在略凸的新骨上可见长时间连续的钙黄蛋白标记,表明OVX + ABL组骨形成基于建模。OVX + ABL组骨形成率/骨面比和基于模型的骨形成位点总长度均高于OVX组。结论阿巴帕肽通过促进骨重建和骨模型形成来抑制卵巢切除术后骨丢失。
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引用次数: 0
Reply to Dr. Nicholas G. Fischer: Letter to “Mirror-polished ceria-stabilized zirconia/alumina nanocomposite enhances gingival junctional epithelial cell adhesion” 回复Dr. Nicholas G. Fischer:致“镜面抛光氧化铈稳定氧化锆/氧化铝纳米复合材料增强牙龈结上皮细胞粘附”的信
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-06-01 Epub Date: 2025-04-11 DOI: 10.1016/j.job.2025.100662
Shoma Yamamori , Eri Urano-Morisawa , Ayako Mochizuki , Ryo Aizawa , Fuminori Iwasa , Matsuo Yamamoto , Kazuyoshi Baba
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引用次数: 0
Impact of DLX3/SAHH axis on osteogenic differentiation of BMSCs in alveolar bone DLX3/SAHH轴对牙槽骨骨髓间充质干细胞成骨分化的影响
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-06-01 Epub Date: 2025-04-01 DOI: 10.1016/j.job.2025.100658
Shichen Sun , Yuxi Jiang , Kang Chen , Xinyi Chen , Jinyou Chai , Haipeng Sun

Objectives

Bone marrow mesenchymal stem cells (BMSCs) promote alveolar bone formation and repair. Distal-less homeobox 3 (DLX3) plays a key regulatory role in BMSC osteogenesis. However, the precise pathway by which it mediates osteogenesis in BMSCs remains unclear. In this study, we investigated the potential epigenetic mechanisms underlying DLX3-mediated BMSCs osteogenesis.

Methods

BMSCs were isolated from the alveolar bone. DLX3 overexpression and knockdown cell lines were established using lentivirus-mediated gene transfer. Osteogenic differentiation was evaluated using alkaline phosphatase expression, alizarin red staining, real-time quantitative polymerase chain reaction, western blotting, chromatin immunoprecipitation, RNA immunoprecipitation, and S-adenosyl-homocysteine hydrolase (SAHH) activity measurements.

Results

DLX3 enhanced the osteogenic differentiation of BMSCs, positively regulated SAHH, and enhancer of zeste homolog 2 (EZH2) activity. In addition, the long non-coding RNA H19 (H19) bound to SAHH in BMSCs. DLX3 regulated the expression of H19, and rescue experiments showed that H19 knockdown increased SAHH activity, thereby promoting osteogenic differentiation in the DLX3-overexpression group.

Conclusions

The DLX3/SAHH axis may regulate the activity of EZH2 involved in the osteogenic differentiation of BMSCs.
目的骨髓间充质干细胞(BMSCs)促进牙槽骨的形成和修复。远端无同源盒3 (DLX3)在BMSC成骨过程中起关键调节作用。然而,它介导骨髓间充质干细胞成骨的确切途径尚不清楚。在这项研究中,我们研究了dlx3介导的骨髓间充质干细胞成骨的潜在表观遗传机制。方法从牙槽骨中分离骨髓间充质干细胞。通过慢病毒介导的基因转移,建立了DLX3过表达和低表达细胞系。采用碱性磷酸酶表达、茜素红染色、实时定量聚合酶链反应、western blotting、染色质免疫沉淀、RNA免疫沉淀和s -腺苷-同型半胱氨酸水解酶(SAHH)活性测定来评估成骨分化。结果dlx3促进骨髓间充质干细胞成骨分化,正向调节SAHH,增强zeste同源物2 (EZH2)活性。此外,在骨髓间充质干细胞中,长链非编码RNA H19 (H19)与SAHH结合。DLX3调节H19的表达,救援实验表明,H19敲低可提高SAHH活性,从而促进DLX3过表达组的成骨分化。结论DLX3/SAHH轴可能调控EZH2的活性,参与骨髓间充质干细胞成骨分化。
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引用次数: 0
Effects of pro-inflammatory cytokines induced by Porphyromonas gingivalis on cell cycle regulation in brain endothelial cells 牙龈卟啉单胞菌诱导的促炎细胞因子对脑内皮细胞周期调控的影响
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-06-01 Epub Date: 2025-05-02 DOI: 10.1016/j.job.2025.100668
Andrea Fernanda Rodríguez , Juan Sebastian Buitrago , Yormaris Castillo , Gloria Inés Lafaurie , Diana Marcela Buitrago-Ramirez

Objectives

Advanced periodontitis potentially contributes to Alzheimer's disease (AD) development and progression by altering the blood–brain barrier microenvironment in the cerebral microvascular endothelium. This results, in cytotoxicity, cell cycle disruption, and increased pro-inflammatory cytokine expression, allowing pathogens to enter the brain and damage the central nervous system (CNS). This study evaluated the effects of Porphyromonas gingivalis W83 infection on pro-inflammatory response, cell viability, and cell cycle regulation in mouse brain endothelial cells (mBECs).

Methods

mBECs were stimulated with live P. gingivalis at different multiplicity of infection (MOI) values (1:5, 1:10, 1:50, 1:100, 1:200) for 6, 12, 24, and 48 h. Cell viability, cell cycle regulation, and pro-inflammatory cytokine mRNA expression were assessed using the alamarBlue assay, flow cytometry, and reverse transcription quantitative polymerase chain reaction (RT-qPCR), respectively.

Results

P. gingivalis reduced cell viability, induced morphological changes in mBECs by >50 % after 48 h (p < 0.05) and caused concentration-dependent arrest in the S and G0/G1 phases of the cell cycle at MOI = 1:100 and 1:200. The Il6, Il1b, and tumor necrosis factor alpha (Tnf) mRNA expression increased significantly compared to that of the controls (p < 0.05).

Conclusions

P. gingivalis reduced cellular metabolism and induced early cell cycle arrest at the G0/G1 phase in mBECs cells. It also increased the pro-inflammatory response, which could be associated with cell death and possible senescence of brain endothelial cells. These results suggested a possible role for P. gingivalis in the pathogenesis of AD. Further studies are required to elucidate these underlying mechanisms.
目的:晚期牙周炎可能通过改变大脑微血管内皮的血脑屏障微环境而促进阿尔茨海默病(AD)的发生和进展。这导致细胞毒性、细胞周期中断和促炎细胞因子表达增加,使病原体进入大脑并损害中枢神经系统(CNS)。本研究评估了牙龈卟啉单胞菌W83感染对小鼠脑内皮细胞(mBECs)的促炎反应、细胞活力和细胞周期调节的影响。方法采用不同感染倍数(MOI)值(1:5、1:10、1:50、1:100、1:200)的活牙龈假单胞菌刺激smbecs 6、12、24和48 h,分别采用alamarBlue法、流式细胞术和逆转录定量聚合酶链反应(RT-qPCR)检测细胞活力、细胞周期调节和促炎细胞因子mRNA表达。48 h后,牙龈炎降低细胞活力,诱导mBECs形态学改变50% (p <;0.05),并在MOI = 1:100和1:200时在细胞周期的S期和G0/G1期引起浓度依赖性阻滞。与对照组相比,il - 6、il - 1b和肿瘤坏死因子α (Tnf) mRNA的表达显著升高(p <;0.05) .ConclusionsP。牙龈炎降低mBECs细胞的细胞代谢,诱导细胞周期早期阻滞在G0/G1期。它还增加了促炎反应,这可能与细胞死亡和可能的脑内皮细胞衰老有关。这些结果提示牙龈假单胞菌可能在AD的发病机制中起作用。需要进一步的研究来阐明这些潜在的机制。
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引用次数: 0
Effects of antigen-induced arthritis and compressive mechanical stress on condylar head of mandible 抗原性关节炎与压应力对下颌骨髁头的影响。
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-06-01 Epub Date: 2025-03-19 DOI: 10.1016/j.job.2025.100654
Shinnosuke Nogami , Tomonari Kajita , Yuta Yanagisawa , Hikari Suzuki , Yuri Takeda , Ko Ito , Akira Kumasaka , Christoph Steiner , Alexander Gaggl , Masahiro Iikubo , Hiroyuki Kumamoto , Kensuke Yamauchi

Objective

Compressive mechanical stress was applied to the temporomandibular joints (TMJ) affected by antigen-induced arthritis to assess the etiological factors of idiopathic condylar resorption.

Methods

Following ovariectomy in 27 female rabbits, 12 received ovalbumin (OVA), 12 received phosphate-buffered saline, and three formed the control group. Each treated rabbit underwent an osteotomy, and a custom device was employed for one week postoperatively, with the length increased by 0.25 mm every 12 h to provide compressive mechanical stress to the TMJ. Thereafter, samples were obtained from the treated groups, subjected to histological staining and immunohistochemistry, and examined using micro-computed tomography.

Results

At each examination, the OVA group showed a greater area and depth of bone resorption, with bone resorption continuing for three weeks following distraction. Additionally, subcondylar bone resorption was noted significantly earlier and had a greater prevalence in the OVA group and greater numbers of tartrate-resistant acid phosphatase-positive cells. Immunostaining for metalloproteinase (MMP)-3 and MMP-13 of the anterior condylar head in the OVA group after two and three weeks revealed high levels of both proteins from the surface to the deep cartilage layer.

Conclusion

Therefore, coexisting TMJ pathology factors, such as antigen-induced arthritis, promote a significantly greater amount of condylar head anterior surface bone resorption.
目的:对受抗原诱发关节炎影响的颞下颌关节(TMJ)施加压缩机械应力,以评估特发性髁突吸收的病因:27只雌性家兔卵巢切除后,12只接受卵清蛋白(OVA)治疗,12只接受磷酸盐缓冲液治疗,3只组成对照组。每只接受治疗的兔子都接受了截骨术,术后一周内使用定制装置,每 12 小时长度增加 0.25 毫米,为颞下颌关节提供压缩机械应力。之后,从治疗组获取样本,进行组织染色和免疫组化,并使用微型计算机断层扫描进行检查:在每次检查中,OVA 组的骨吸收面积更大、深度更深,骨吸收在牵引后持续三周。此外,OVA 组的髁突下骨吸收明显更早,发生率更高,抗酒石酸磷酸酶阳性细胞的数量也更多。OVA组在两周和三周后对髁状突前头部的金属蛋白酶(MMP)-3和MMP-13进行免疫染色,结果显示从表面到软骨深层这两种蛋白的含量都很高:因此,同时存在的颞下颌关节病理因素,如抗原诱发的关节炎,会明显促进髁状突头前表面骨吸收。
{"title":"Effects of antigen-induced arthritis and compressive mechanical stress on condylar head of mandible","authors":"Shinnosuke Nogami ,&nbsp;Tomonari Kajita ,&nbsp;Yuta Yanagisawa ,&nbsp;Hikari Suzuki ,&nbsp;Yuri Takeda ,&nbsp;Ko Ito ,&nbsp;Akira Kumasaka ,&nbsp;Christoph Steiner ,&nbsp;Alexander Gaggl ,&nbsp;Masahiro Iikubo ,&nbsp;Hiroyuki Kumamoto ,&nbsp;Kensuke Yamauchi","doi":"10.1016/j.job.2025.100654","DOIUrl":"10.1016/j.job.2025.100654","url":null,"abstract":"<div><h3>Objective</h3><div>Compressive mechanical stress was applied to the temporomandibular joints (TMJ) affected by antigen-induced arthritis to assess the etiological factors of idiopathic condylar resorption.</div></div><div><h3>Methods</h3><div>Following ovariectomy in 27 female rabbits, 12 received ovalbumin (OVA), 12 received phosphate-buffered saline, and three formed the control group. Each treated rabbit underwent an osteotomy, and a custom device was employed for one week postoperatively, with the length increased by 0.25 mm every 12 h to provide compressive mechanical stress to the TMJ. Thereafter, samples were obtained from the treated groups, subjected to histological staining and immunohistochemistry, and examined using micro-computed tomography.</div></div><div><h3>Results</h3><div>At each examination, the OVA group showed a greater area and depth of bone resorption, with bone resorption continuing for three weeks following distraction. Additionally, subcondylar bone resorption was noted significantly earlier and had a greater prevalence in the OVA group and greater numbers of tartrate-resistant acid phosphatase-positive cells. Immunostaining for metalloproteinase (MMP)-3 and MMP-13 of the anterior condylar head in the OVA group after two and three weeks revealed high levels of both proteins from the surface to the deep cartilage layer.</div></div><div><h3>Conclusion</h3><div>Therefore, coexisting TMJ pathology factors, such as antigen-induced arthritis, promote a significantly greater amount of condylar head anterior surface bone resorption.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 2","pages":"Article 100654"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Role of glucose metabolism in amelogenesis 葡萄糖代谢在淀粉形成中的作用
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-06-01 Epub Date: 2025-04-28 DOI: 10.1016/j.job.2025.100667
Hiroko Ida-Yonemochi

Background

Cell energy metabolism plays a pivotal role in organ development and function by regulating cell behavior in pathophysiological conditions. Glucose metabolism is the central cascade for obtaining energy in mammalian cells, and cells alter the glucose metabolic pathway depending on intra- and extracellular environments. Therefore, glucose metabolism is closely associated with cell differentiation stages, and cell energy metabolism plays a vital role not only in energy production but also in cell fate regulation in organogenesis.

Highlight

During enamel formation, the timing of the expression of passive and active glucose transporters, glycogen synthesis, and glycogen degradation is strictly regulated according to the energy demand of ameloblast-lineage cells. These glucose metabolic reactions are particularly active in the maturation stage of ameloblasts. Furthermore, autophagy, a key regulator of cellular energy homeostasis that modulates glucose metabolism, occurs during both the secretory and maturation stages of ameloblasts. Disruption of glucose metabolism cascade and autophagy induces enamel hypoplasia, as demonstrated in both in vitro and in vivo models.

Conclusion

Adequate energy supply via glucose metabolism is essential for enamel matrix secretion and maturation. A thorough understanding of the precise regulation of energy metabolism in amelogenesis facilitates comprehension of the normal enamel formation process and pathological conditions affecting it. This review summarizes glucose metabolic processes during amelogenesis, focusing on glucose uptake, glycogenesis, and glycogenolysis.
细胞能量代谢通过调节病理生理条件下的细胞行为,在器官发育和功能中起着关键作用。葡萄糖代谢是哺乳动物细胞获取能量的核心级联,细胞根据细胞内和细胞外环境改变葡萄糖代谢途径。因此,葡萄糖代谢与细胞分化阶段密切相关,细胞能量代谢不仅在能量产生中起着重要作用,而且在器官发生过程中对细胞命运的调节也起着至关重要的作用。在牙釉质形成过程中,被动和主动葡萄糖转运蛋白的表达、糖原合成和糖原降解的时间受到成釉细胞能量需求的严格调控。这些葡萄糖代谢反应在成釉细胞成熟阶段尤为活跃。此外,自噬是调节葡萄糖代谢的细胞能量稳态的关键调节因子,发生在成釉细胞的分泌和成熟阶段。体外和体内模型均证实,糖代谢级联和自噬的破坏可诱导牙釉质发育不全。结论糖代谢对牙釉质基质分泌和成熟有重要作用。深入了解成釉过程中能量代谢的精确调控有助于理解正常的牙釉质形成过程和影响牙釉质形成的病理条件。本文综述了淀粉发生过程中的葡萄糖代谢过程,重点介绍了葡萄糖摄取、糖原发生和糖原分解。
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引用次数: 0
Chemokine receptor 5 signaling in oral diseases and degenerative temporomandibular joint disease 趋化因子受体5信号在口腔疾病和退行性颞下颌关节疾病中的作用
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-06-01 Epub Date: 2025-04-24 DOI: 10.1016/j.job.2025.100666
Haruhisa Watanabe , Riyu Koguchi , Takashi S. Kajii , Yutaka Maruoka , Tadahiro Iimura

Background

Chemokine receptor 5 (CCR5)-mediated signals are involved in various biological responses and inflammatory diseases. Recent studies have revealed the roles of this signaling pathway in bone metabolism, metabolic bone diseases, and joint diseases.

Highlight

Through preclinical and clinical studies, our research group has demonstrated that CCR5 signaling is deeply involved in degenerative changes in the temporomandibular joint (TMJ).

Conclusion

In this short review, we outline the diverse functions of CCR5 signaling in oral and degenerative TMJ diseases.
趋化因子受体5 (CCR5)介导的信号参与多种生物反应和炎症性疾病。近年来的研究揭示了该信号通路在骨代谢、代谢性骨病和关节疾病中的作用。通过临床前和临床研究,本课课组已证实CCR5信号通路深度参与颞下颌关节(TMJ)退行性改变。在这篇简短的综述中,我们概述了CCR5信号在口腔和退行性TMJ疾病中的多种功能。
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引用次数: 0
Saliva composition from birth to adolescence: a systematic review of the literature 唾液组成从出生到青春期:文献的系统回顾。
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-06-01 Epub Date: 2025-04-03 DOI: 10.1016/j.job.2025.100661
Samira Moradi , Floris J. Bikker , Daniela Hesse

Background

This systematic review examined the saliva composition of healthy children from birth to 18 years of age by assessing the salivary flow rate, pH, buffering capacity, and ion levels. This review followed the PRISMA guidelines. A systematic search was performed using PubMed, the Cochrane Library, and Scopus. Information regarding the salivary flow rate, pH, buffering capacity, and ion levels in whole saliva was systematically collected, and a qualitative synthesis was performed. The methodological quality of the studies was assessed using the JBI Critical Appraisal Tools.

Highlight

Of the 3,268 retrieved studies, 41 were eligible for inclusion. Unstimulated salivary flow showed an age-related decrease, whereas stimulated salivary flow increased with age. The pH of the saliva remained consistent across different ages, whereas the buffering capacity showed an age-related increase. Salivary sodium, calcium, and potassium levels were lower in the younger children than in the older children. An investigation of salivary ion levels revealed lower average fluoride concentrations in Asian populations than in European populations. Most studies had a low or moderate risk of bias.

Conclusion

This systematic review highlights age-dependent differences in salivary flow and composition in healthy children from birth to 18 years of age. The flow rate of unstimulated saliva decreased with age, while the flow rate of stimulated saliva increased. The salivary pH remained stable, whereas the buffering capacity increased with age. Furthermore, salivary sodium, calcium, and potassium levels tend to increase with age. These findings underscore the dynamic nature of salivary composition from childhood to adolescence.
背景:本系统综述通过评估唾液流速、pH 值、缓冲能力和离子水平,研究了出生至 18 岁健康儿童的唾液组成。本综述遵循 PRISMA 指南。我们使用 PubMed、Cochrane 图书馆和 Scopus 进行了系统检索。系统收集了有关唾液流速、pH 值、缓冲能力和整个唾液中离子水平的信息,并进行了定性综合。研究的方法学质量采用 JBI 关键评估工具(JBI Critical Appraisal Tools.Highlight)进行评估:在检索到的 3268 项研究中,有 41 项符合纳入条件。未受刺激的唾液流量随年龄增长而减少,而受刺激的唾液流量则随年龄增长而增加。唾液的 pH 值在不同年龄段保持一致,而缓冲能力则随着年龄的增长而增加。低龄儿童唾液中的钠、钙和钾含量低于高龄儿童。对唾液离子水平的调查显示,亚洲人的平均氟浓度低于欧洲人。大多数研究存在低度或中度偏倚风险:本系统综述强调了健康儿童(从出生到 18 岁)唾液流量和组成的年龄差异。随着年龄的增长,非刺激性唾液的流速下降,而刺激性唾液的流速上升。唾液的 pH 值保持稳定,而缓冲能力则随着年龄的增长而增加。此外,唾液中的钠、钙和钾含量也会随着年龄的增长而增加。这些发现强调了唾液成分从儿童期到青春期的动态性质。
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引用次数: 0
Vascular inflammation and cancer malignancy 血管炎症和恶性肿瘤
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-06-01 Epub Date: 2025-05-20 DOI: 10.1016/j.job.2025.100671
Yuya Sakurai , Li Yu , Aya Matsuda , Nako Maishi , Kyoko Hida

Background

Vascular inflammation is a key contributor to cancer progression and metastasis. Tumor endothelial cells (TECs) respond to microbial, metabolic, and therapeutic stimuli by upregulating adhesion molecules and cytokines, which facilitates tumor cell adhesion and immune evasion.

Highlight

This review focuses on three representative vascular inflammatory triggers: Streptococcus mutans-induced endothelial activation, the oxLDL/LOX-1 signaling axis, and chemotherapy-induced vascular dysfunction. These mechanisms converge to establish a pre-metastatic niche. Emerging strategies including microbiota modulation, metabolic targeting, and low-dose metronomic (LDM) chemotherapy, have shown promise in preclinical studies for preserving vascular integrity and reducing inflammation.

Conclusion

Targeting vascular inflammation is a novel therapeutic approach to suppressing metastasis and cardiovascular events. Further studies are required to validate predictive biomarkers and optimize these strategies for clinical applications.
背景:血管炎症是癌症进展和转移的关键因素。肿瘤内皮细胞(tec)通过上调粘附分子和细胞因子对微生物、代谢和治疗刺激做出反应,从而促进肿瘤细胞的粘附和免疫逃逸。本文综述了三种具有代表性的血管炎症触发因素:变形链球菌诱导的内皮激活、oxLDL/LOX-1信号轴和化疗诱导的血管功能障碍。这些机制共同建立了转移前生态位。包括微生物群调节、代谢靶向和低剂量节律化疗在内的新兴策略在临床前研究中显示出保持血管完整性和减少炎症的希望。结论靶向血管炎症是抑制血管转移和心血管事件的新途径。需要进一步的研究来验证预测性生物标志物并优化这些策略以用于临床应用。
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引用次数: 0
Identification of PilX, pilus component of Streptococcus sanguinis 血链球菌菌毛成分PilX的鉴定
IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-06-01 Epub Date: 2025-04-18 DOI: 10.1016/j.job.2025.100664
Li Yixuan , Masanobu Nakata , Hirono Migita , Airi Matsumoto , Yuichi Oogai , Katsuki Takebe , Masaya Yamaguchi , Nobuo Okahashi , Tomoko Sumitomo , Shigetada Kawabata

Objectives

Streptococcus sanguinis is an oral commensal bacterium that promotes dental biofilm formation and causes infective endocarditis. S. sanguinis strain SK36 produces pili comprising PilA, PilB, and PilC. This study determined whether the ssa1635 gene adjacent to the pilus-related gene locus encodes a pilus component and its roles in biofilm formation and eukaryotic cell adhesion.

Methods

Using a series of mutant strains and antisera against PilA, PilB, PilC, and SSA1635, immunoblot analyses and immunoprecipitation assays were performed for SSA1635 characterization. Both involvement of the deduced pilus-specific transpeptidase SrtC in pilus assembly and SSA1635 localization were examined by immunoblot analysis of various mutant strains. Furthermore, biofilm formation assays on saliva-coated surfaces and adhesion to HeLa cells were conducted to assess functions.

Results

SSA1635, designated as PilX, formed complexes with PilA, PilB, and PilC. PilX was identified as a tip pilin incorporated into the pilus structure by SrtC. Notably, deletion of pilX impaired polymerization of other pilins. Furthermore, a pilX deletion mutant exhibited decreased biofilm formation compared with the wild-type and revertant strains and comparable rates of adherence to HeLa cells.

Conclusions

PilX is a potential pilin tip that may aid in facilitating the polymerization of other pilins. PilX contributes to biofilm formation, although it appears to be dispensable for adhesion to HeLa cells. Further characterization of PilX-binding specificities will provide valuable insights into the colonization mechanism of S. sanguinis.
目的:血链球菌是一种促进口腔生物膜形成并引起感染性心内膜炎的口腔共生菌。血链球菌菌株SK36产生由PilA、PilB和PilC组成的毛。本研究确定了菌毛相关基因位点附近的ssa1635基因是否编码菌毛成分及其在生物膜形成和真核细胞粘附中的作用。方法利用一系列突变株和抗PilA、PilB、PilC和SSA1635的抗血清,采用免疫印迹和免疫沉淀法对SSA1635进行鉴定。利用免疫印迹法检测了不同突变株的菌毛转肽酶SrtC在菌毛组装中的作用和SSA1635的定位。此外,通过唾液包被表面的生物膜形成和与HeLa细胞的粘附来评估其功能。结果sssa1635与PilA、PilB、PilC形成配合物,命名为PilX。通过SrtC鉴定,PilX是一种嵌入到菌毛结构中的尖端菌毛。值得注意的是,pilX的缺失损害了其他pilins的聚合。此外,与野生型和逆转菌株相比,pilX缺失突变株的生物膜形成减少,与HeLa细胞的粘附率也相当。结论spilx是一种潜在的药柱尖端,可能有助于促进其他药柱的聚合。PilX有助于生物膜的形成,尽管它对HeLa细胞的粘附似乎是必不可少的。进一步表征pilx结合特异性将为血链球菌的定植机制提供有价值的见解。
{"title":"Identification of PilX, pilus component of Streptococcus sanguinis","authors":"Li Yixuan ,&nbsp;Masanobu Nakata ,&nbsp;Hirono Migita ,&nbsp;Airi Matsumoto ,&nbsp;Yuichi Oogai ,&nbsp;Katsuki Takebe ,&nbsp;Masaya Yamaguchi ,&nbsp;Nobuo Okahashi ,&nbsp;Tomoko Sumitomo ,&nbsp;Shigetada Kawabata","doi":"10.1016/j.job.2025.100664","DOIUrl":"10.1016/j.job.2025.100664","url":null,"abstract":"<div><h3>Objectives</h3><div><em>Streptococcus sanguinis</em> is an oral commensal bacterium that promotes dental biofilm formation and causes infective endocarditis. <em>S. sanguinis</em> strain SK36 produces pili comprising PilA, PilB, and PilC. This study determined whether the <em>ssa</em>1635 gene adjacent to the pilus-related gene locus encodes a pilus component and its roles in biofilm formation and eukaryotic cell adhesion.</div></div><div><h3>Methods</h3><div>Using a series of mutant strains and antisera against PilA, PilB, PilC, and SSA1635, immunoblot analyses and immunoprecipitation assays were performed for SSA1635 characterization. Both involvement of the deduced pilus-specific transpeptidase SrtC in pilus assembly and SSA1635 localization were examined by immunoblot analysis of various mutant strains. Furthermore, biofilm formation assays on saliva-coated surfaces and adhesion to HeLa cells were conducted to assess functions.</div></div><div><h3>Results</h3><div>SSA1635, designated as PilX, formed complexes with PilA, PilB, and PilC. PilX was identified as a tip pilin incorporated into the pilus structure by SrtC. Notably, deletion of <em>pilX</em> impaired polymerization of other pilins. Furthermore, a <em>pilX</em> deletion mutant exhibited decreased biofilm formation compared with the wild-type and revertant strains and comparable rates of adherence to HeLa cells.</div></div><div><h3>Conclusions</h3><div>PilX is a potential pilin tip that may aid in facilitating the polymerization of other pilins. PilX contributes to biofilm formation, although it appears to be dispensable for adhesion to HeLa cells. Further characterization of PilX-binding specificities will provide valuable insights into the colonization mechanism of <em>S. sanguinis</em>.</div></div>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":"67 2","pages":"Article 100664"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Journal of Oral Biosciences
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