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Spatiotemporal cellular dynamics and molecular regulation of tooth root ontogeny. 牙根发生的时空细胞动力学与分子调控。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-11-24 DOI: 10.1038/s41368-023-00258-9
Pengcheng Rao, Junjun Jing, Yi Fan, Chenchen Zhou

Tooth root development involves intricate spatiotemporal cellular dynamics and molecular regulation. The initiation of Hertwig's epithelial root sheath (HERS) induces odontoblast differentiation and the subsequent radicular dentin deposition. Precisely controlled signaling pathways modulate the behaviors of HERS and the fates of dental mesenchymal stem cells (DMSCs). Disruptions in these pathways lead to defects in root development, such as shortened roots and furcation abnormalities. Advances in dental stem cells, biomaterials, and bioprinting show immense promise for bioengineered tooth root regeneration. However, replicating the developmental intricacies of odontogenesis has not been resolved in clinical treatment and remains a major challenge in this field. Ongoing research focusing on the mechanisms of root development, advanced biomaterials, and manufacturing techniques will enable next-generation biological root regeneration that restores the physiological structure and function of the tooth root. This review summarizes recent discoveries in the underlying mechanisms governing root ontogeny and discusses some recent key findings in developing of new biologically based dental therapies.

牙根发育涉及复杂的时空细胞动力学和分子调控。Hertwig’s上皮根鞘(Hertwig’s epithelial root sheath, HERS)的形成诱导成牙细胞分化和随后的根状牙本质沉积。精确控制的信号通路调节HERS的行为和牙间充质干细胞(DMSCs)的命运。这些通路的中断会导致根发育缺陷,如根变短和功能异常。牙干细胞、生物材料和生物打印技术的进步为生物工程牙根再生提供了巨大的希望。然而,在临床治疗中,复制牙形成的复杂发育尚未得到解决,这仍然是该领域的主要挑战。目前正在进行的关于牙根发育机制、先进生物材料和制造技术的研究将使下一代生物牙根再生成为可能,从而恢复牙根的生理结构和功能。本文综述了近年来在牙根发生机制方面的最新发现,并讨论了最近在发展新的基于生物学的牙科治疗方面的一些重要发现。
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引用次数: 0
Titanium particles in peri-implantitis: distribution, pathogenesis and prospects 钛颗粒在种植体周围炎中的分布、发病机制及前景
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-11-23 DOI: 10.1038/s41368-023-00256-x
Long Chen, Zian Tong, Hongke Luo, Yuan Qu, Xinhua Gu, Misi Si

Peri-implantitis is one of the most important biological complications in the field of oral implantology. Identifying the causative factors of peri-implant inflammation and osteolysis is crucial for the disease’s prevention and treatment. The underlying risk factors and detailed pathogenesis of peri-implantitis remain to be elucidated. Titanium-based implants as the most widely used implant inevitably release titanium particles into the surrounding tissue. Notably, the concentration of titanium particles increases significantly at peri-implantitis sites, suggesting titanium particles as a potential risk factor for the condition. Previous studies have indicated that titanium particles can induce peripheral osteolysis and foster the development of aseptic osteoarthritis in orthopedic joint replacement. However, it remains unconfirmed whether this phenomenon also triggers inflammation and bone resorption in peri-implant tissues. This review summarizes the distribution of titanium particles around the implant, the potential roles in peri-implantitis and the prevalent prevention strategies, which expects to provide new directions for the study of the pathogenesis and treatment of peri-implantitis.

种植体周围炎是口腔种植领域最重要的生物学并发症之一。确定种植体周围炎症和骨溶解的致病因素对疾病的预防和治疗至关重要。种植体周围炎的潜在危险因素和详细的发病机制仍有待阐明。钛基种植体是目前应用最广泛的种植体,不可避免地会向周围组织释放钛颗粒。值得注意的是,钛颗粒浓度在种植体周围明显增加,提示钛颗粒是该疾病的潜在危险因素。已有研究表明,在骨科关节置换术中,钛颗粒可诱导外周骨溶解,促进无菌性骨关节炎的发生。然而,这种现象是否也会引发种植体周围组织的炎症和骨吸收尚不确定。本文综述了钛颗粒在种植体周围的分布、在种植体周围炎中的潜在作用以及目前常见的预防策略,以期为种植体周围炎的发病机制和治疗研究提供新的方向。
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引用次数: 0
Massive MIMO-OFDM Transmission Without Cellular Networks Using Frequency - Selective Fading Channels 无蜂窝网络下使用频率选择性衰落信道的大规模MIMO-OFDM传输
1区 医学 Q1 Dentistry Pub Date : 2023-10-31 DOI: 10.22214/ijraset.2023.56225
Dr. M. VijayaLakshmi, C. Anisha
Abstract: For cell-free massive multi-input multi-output (CF-m-MIMO) across frequency-selective fading channels, this system introduces and determines the effectiveness of the orthogonal frequency-division multiplexing (OFDM)-based multi-carrier transmission. The CF-m-MIMO-OFDM system can accommodate a substantial user base and is flexible enough to offer a range of data rates for usage in a variety of contexts. With its scalability and flexibility, the CF-m-MIMO-OFDM transmission network can serve a large number of users at variable data rates. It is proposed to beamform in the frequency-domain conjugate, to choose a pilot, and to allocate resources differently for each user. User-specific resource allocation, pilot selection, and frequency-domain conjugate beamforming are all suggested. The CF-m-MIMO-OFDM system can support a large number of users and can offer varying data rates to accommodate a wide range of applications.
摘要:针对无小区大规模多输入多输出(CF-m-MIMO)跨频率选择性衰落信道,介绍并确定了基于正交频分复用(OFDM)的多载波传输的有效性。CF-m-MIMO-OFDM系统可以容纳大量的用户群,并且足够灵活,可以在各种环境中提供一系列数据速率。CF-m-MIMO-OFDM传输网络具有可扩展性和灵活性,能够以可变数据速率为大量用户提供服务。提出了在频域共轭中进行波束形成、选择导频、为每个用户分配不同的资源等方法。用户特定的资源分配、导频选择和频域共轭波束形成都是建议。CF-m-MIMO-OFDM系统可以支持大量用户,并可以提供不同的数据速率,以适应广泛的应用。
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引用次数: 0
MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1. MLL1通过与WDR5相互作用和抑制HES1来抑制SCAPs的神经源性潜能。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-10-18 DOI: 10.1038/s41368-023-00253-0
Chen Zhang, Weilong Ye, Mengyao Zhao, Lujue Long, Dengsheng Xia, Zhipeng Fan

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising treatment for spinal cord injury (SCI), but improving the neurogenic potential of MSCs remains a challenge. Mixed lineage leukemia 1 (MLL1), an H3K4me3 methyltransferases, plays a critical role in regulating lineage-specific gene expression and influences neurogenesis. In this study, we investigated the role and mechanism of MLL1 in the neurogenesis of stem cells from apical papilla (SCAPs). We examined the expression of neural markers, and the nerve repair and regeneration ability of SCAPs using dynamic changes in neuron-like cells, immunofluorescence staining, and a SCI model. We employed a coimmunoprecipitation (Co-IP) assay, real-time RT-PCR, microarray analysis, and chromatin immunoprecipitation (ChIP) assay to investigate the molecular mechanism. The results showed that MLL1 knock-down increased the expression of neural markers, including neurogenic differentiation factor (NeuroD), neural cell adhesion molecule (NCAM), tyrosine hydroxylase (TH), βIII-tubulin and Nestin, and promoted neuron-like cell formation in SCAPs. In vivo, a transplantation experiment showed that depletion of MLL 1 in SCAPs can restore motor function in a rat SCI model. MLL1 can combine with WD repeat domain 5 (WDR5) and WDR5 inhibit the expression of neural markers in SCAPs. MLL1 regulates Hairy and enhancer of split 1 (HES1) expression by directly binds to HES1 promoters via regulating H3K4me3 methylation by interacting with WDR5. Additionally, HES1 enhances the expression of neural markers in SCAPs. Our findings demonstrate that MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1. These results provide a potential therapeutic target for promoting the recovery of motor function in SCI patients.

基于间充质干细胞(MSC)的治疗已成为治疗脊髓损伤(SCI)的一种有前途的方法,但提高MSC的神经源性潜力仍然是一个挑战。混合谱系白血病1(MLL1)是一种H3K4me3甲基转移酶,在调节谱系特异性基因表达和影响神经发生方面发挥着关键作用。在本研究中,我们研究了MLL1在根尖乳头干细胞(SCAPs)神经发生中的作用和机制。我们使用神经元样细胞的动态变化、免疫荧光染色和SCI模型检测了神经标记物的表达以及SCAP的神经修复和再生能力。我们采用共免疫沉淀(Co-IP)分析、实时RT-PCR、微阵列分析和染色质免疫沉淀(ChIP)分析来研究其分子机制。结果表明,MLL1敲除增加了神经源性分化因子(NeuroD)、神经细胞粘附分子(NCAM)、酪氨酸羟化酶(TH)、βIII微管蛋白和巢蛋白等神经标志物的表达,并促进了SCAPs中神经元样细胞的形成。体内移植实验表明,SCAPs中MLL1的缺失可以恢复大鼠SCI模型的运动功能。MLL1可以与WD重复结构域5(WDR5)结合,WDR5抑制SCAP中神经标志物的表达。MLL1通过与WDR5相互作用调节H3K4me3甲基化,直接与HES1启动子结合,从而调节Hairy和分裂1增强子(HES1)的表达。此外,HES1增强了SCAP中神经标记物的表达。我们的研究结果表明,MLL1通过与WDR5相互作用和抑制HES1来抑制SCAPs的神经源性潜力。这些结果为促进SCI患者运动功能的恢复提供了一个潜在的治疗靶点。
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引用次数: 0
Sclerostin antibody improves alveolar bone quality in the Hyp mouse model of X-linked hypophosphatemia (XLH). 在X连锁低磷血症(XLH)的Hyp小鼠模型中,硬化蛋白抗体可改善牙槽骨质量。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-10-10 DOI: 10.1038/s41368-023-00252-1
Kelsey A Carpenter, Delia O Alkhatib, Bryan A Dulion, Elizabeth Guirado, Shreya Patel, Yinghua Chen, Anne George, Ryan D Ross

X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads to hypophosphatemia and impaired mineralization of bone and teeth. The clinical manifestations of XLH include a high prevalence of dental abscesses and periodontal disease, likely driven by poorly formed structures of the dentoalveolar complex, including the alveolar bone, cementum, dentin, and periodontal ligament. Our previous studies have demonstrated that sclerostin antibody (Scl-Ab) treatment improves phosphate homeostasis, and increases long bone mass, strength, and mineralization in the Hyp mouse model of XLH. In the current study, we investigated whether Scl-Ab impacts the dentoalveolar structures of Hyp mice. Male and female wild-type and Hyp littermates were injected with 25 mg·kg-1 of vehicle or Scl-Ab twice weekly beginning at 12 weeks of age and euthanized at 20 weeks of age. Scl-Ab increased alveolar bone mass in both male and female mice and alveolar tissue mineral density in the male mice. The positive effects of Scl-Ab were consistent with an increase in the fraction of active (nonphosphorylated) β-catenin, dentin matrix protein 1 (DMP1) and osteopontin stained alveolar osteocytes. Scl-Ab had no effect on the mass and mineralization of dentin, enamel, acellular or cellular cementum. There was a nonsignificant trend toward increased periodontal ligament (PDL) attachment fraction within the Hyp mice. Additional PDL fiber structural parameters were not affected by Scl-Ab. The current study demonstrates that Scl-Ab can improve alveolar bone in adult Hyp mice.

X连锁低磷血症(XLH)是一种罕见的成纤维细胞生长因子23(FGF23)产生增加的疾病,可导致低磷血症和骨和牙齿矿化受损。XLH的临床表现包括牙脓肿和牙周病的高发病率,这可能是由牙-牙槽复合体的不良结构引起的,包括牙槽骨、牙骨质、牙本质和牙周膜。我们之前的研究表明,硬化素抗体(Scl-Ab)治疗改善了XLH Hyp小鼠模型中的磷酸盐稳态,并增加了长骨质量、强度和矿化。在目前的研究中,我们研究了Scl-Ab是否会影响Hyp小鼠的齿杆结构。雄性和雌性野生型和Hyp同窝仔注射25 mg·kg-1的载体或Scl-Ab,从12周龄开始每周两次,并在20周龄时实施安乐死。Scl-Ab增加了雄性和雌性小鼠的肺泡骨量和雄性小鼠的肺泡组织矿物质密度。Scl-Ab的积极作用与活性(非磷酸化)β-连环蛋白、牙本质基质蛋白1(DMP1)和骨桥蛋白染色的肺泡骨细胞的比例增加一致。Scl-Ab对牙本质、牙釉质、脱细胞或细胞牙骨质的质量和矿化没有影响。在Hyp小鼠体内,牙周膜(PDL)附着分数增加的趋势并不显著。附加的PDL纤维结构参数不受Scl-Ab的影响。目前的研究表明Scl-Ab可以改善成年Hyp小鼠的牙槽骨。
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引用次数: 0
Forming linguistic-cultural competencies in Kazakhstani students learning Russian as a non-native language 哈萨克斯坦学生学习俄语作为非母语的语言文化能力的形成
1区 医学 Q1 Dentistry Pub Date : 2023-09-30 DOI: 10.22363/2618-8163-2023-21-3-341-355
Rimma A. Arynbayeva, Zhanna K. Makhanova, Natalya V. Dmitryuk
The formation of linguistic-cultural competence in the process of teaching Russian as a non-native language is becoming a priority in modern linguodidactics, in particular in the educational space of Kazakhstan. The relevance of the study is in the need to form and develop a fully educated secondary linguistic personality in the multilingual environment of modern society. This requires applying anthropocentric principle in teaching Russian as a linguistic-cultural phenomenon. The aim of the study is to form students' linguistic-cultural competence in precepting the features of the Russian picture of the world, traditional values, and mentality of the Russian ethnic group. The material of the study includes associative dictionaries of the Russian and Kazakh languages, the results of associative experiments with schoolchildren, scientific sources on psycholinguistics and cultural linguistics, Kazakh manuals and textbooks on the Russian language (in schools with Russian/Kazakh language of teaching). In the work comparative and associative experiments, pilot survey were used, as well as the methods of structuring (associative semantic gestalt according to the method of Yu.N. Karaulov), linguistic and cultural commentary, modeling situational exercises and analysis of communicative-speech acts. The results of the study illustrate the specificity of students' ethnolinguistic awareness at the associative level. The relevance of linguistic and cultural commentary for widening students' ethno-mental outlook and organising adequate intercultural dialogues is grounded. The effectiveness of associative experiments materials as a means of forming linguistic-cultural competence of students is shown.
在俄语非母语教学过程中,语言文化能力的形成正在成为现代语言教学的重点,特别是在哈萨克斯坦的教育领域。该研究的意义在于,在现代社会的多语言环境中,需要形成和发展一个受过充分教育的第二语言人格。这就要求在俄语这一语言文化现象的教学中运用人类中心主义原则。本课程旨在培养学生对俄罗斯世界观、传统价值观和俄罗斯民族心理特征的语言文化认知能力。研究的材料包括俄语和哈萨克语的联想词典、小学生联想实验的结果、心理语言学和文化语言学的科学资料、哈萨克语手册和俄语教科书(在俄语/哈萨克语教学的学校)。在工作比较实验和联想实验中,采用了先导调查法,并根据俞氏的方法构建联想语义格式塔。Karaulov),语言和文化评论,情景模拟练习和交际言语行为分析。本研究结果说明了学生民族语言意识在联想层面的特殊性。语言和文化评论对于扩大学生的民族精神视野和组织适当的跨文化对话的相关性是有根据的。实验结果表明,联想实验材料是培养学生语言文化能力的有效手段。
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引用次数: 1
Double heterozygous pathogenic mutations in KIF3C and ZNF513 cause hereditary gingival fibromatosis. KIF3C和ZNF513的双重杂合致病突变可引起遗传性牙龈纤维瘤病。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-09-26 DOI: 10.1038/s41368-023-00244-1
Jianfan Chen, Xueqing Xu, Song Chen, Ting Lu, Yingchun Zheng, Zhongzhi Gan, Zongrui Shen, Shunfei Ma, Duocai Wang, Leyi Su, Fei He, Xuan Shang, Huiyong Xu, Dong Chen, Leitao Zhang, Fu Xiong

Hereditary gingival fibromatosis (HGF) is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity. Five distinct loci related to non-syndromic HGF have been identified; however, only two disease-causing genes, SOS1 and REST, inducing HGF have been identified at two loci, GINGF1 and GINGF5, respectively. Here, based on a family pedigree with 26 members, including nine patients with HGF, we identified double heterozygous pathogenic mutations in the ZNF513 (c.C748T, p.R250W) and KIF3C (c.G1229A, p.R410H) genes within the GINGF3 locus related to HGF. Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo. ZNF513, a transcription factor, binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts. Furthermore, a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513 (p.R250W) or Kif3c (p.R412H) alone do not led to clear phenotypes with gingival fibromatosis, whereas the double mutations led to gingival hyperplasia phenotypes. In addition, we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1. Moreover, the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels. ZNF513 combined with KIF3C regulates gingival fibroblast proliferation, migration, and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways. In summary, these results demonstrate ZNF513 + KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.

遗传性牙龈纤维瘤病(HGF)是一种罕见的牙龈组织纤维瘤样增生的遗传性疾病,表现出巨大的遗传异质性。已经鉴定了五个与非综合征HGF相关的不同基因座;然而,在GINGF1和GINGF5两个基因座上,仅鉴定出两个诱导HGF的致病基因,即SOS1和REST。在这里,基于一个有26名成员的家族谱系,包括9名HGF患者,我们在与HGF相关的GINGF3基因座内的ZNF513(c.C748T,p.R250W)和KIF3C(c.G1229A,p.R410H)基因中鉴定了双杂合致病突变。功能研究表明,ZNF513 p.R250W和KIF3C p.R410H变体在体外和体内显著增加了ZNF513和KIF3C的表达。ZNF513是一种转录因子,与KIF3C外显子1结合,参与牙龈成纤维细胞中KIF3C表达的正调控。此外,敲除小鼠模型证实,Zfp513(p.R250W)或Kif3c(p.R412H)内的杂合或纯合突变单独不会导致牙龈纤维瘤病的明确表型,而双重突变导致牙龈增生表型。此外,我们发现ZNF513与SOS1启动子结合,并在调节SOS1的表达方面发挥重要的积极作用。此外,KIF3C p.R410H突变可以激活PI3K和KCNQ1钾通道。ZNF513与KIF3C联合通过PI3K/AKT/mTOR和Ras/Raf/MEK/ERK途径调节牙龈成纤维细胞增殖、迁移和纤维化反应。总之,这些结果证明了ZNF513 + KIF3C是HGF表现中的重要基因组合,提示ZNF513突变可能是HGF的主要危险因素。
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引用次数: 0
Transcriptional profiling of dental sensory and proprioceptive trigeminal neurons using single-cell RNA sequencing. 使用单细胞RNA测序的牙齿感觉和本体感觉三叉神经神经元的转录谱。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-09-25 DOI: 10.1038/s41368-023-00246-z
Pa Reum Lee, Jihoon Kim, Heather Lynn Rossi, Sena Chung, Seung Yub Han, Junhyong Kim, Seog Bae Oh

Dental primary afferent (DPA) neurons and proprioceptive mesencephalic trigeminal nucleus (MTN) neurons, located in the trigeminal ganglion and the brainstem, respectively, are essential for controlling masticatory functions. Despite extensive transcriptomic studies on various somatosensory neurons, there is still a lack of knowledge about the molecular identities of these populations due to technical challenges in their circuit-validated isolation. Here, we employed high-depth single-cell RNA sequencing (scRNA-seq) in combination with retrograde tracing in mice to identify intrinsic transcriptional features of DPA and MTN neurons. Our transcriptome analysis revealed five major types of DPA neurons with cell type-specific gene enrichment, some of which exhibit unique mechano-nociceptive properties capable of transmitting nociception in response to innocuous mechanical stimuli in the teeth. Furthermore, we discovered cellular heterogeneity within MTN neurons that potentially contribute to their responsiveness to mechanical stretch in the masseter muscle spindles. Additionally, DPA and MTN neurons represented sensory compartments with distinct molecular profiles characterized by various ion channels, receptors, neuropeptides, and mechanoreceptors. Together, our study provides new biological insights regarding the highly specialized mechanosensory functions of DPA and MTN neurons in pain and proprioception.

牙齿初级传入(DPA)神经元和本体感觉中脑三叉神经核(MTN)神经元分别位于三叉神经节和脑干,对控制咀嚼功能至关重要。尽管对各种体感神经元进行了广泛的转录组学研究,但由于电路验证分离的技术挑战,对这些群体的分子身份仍然缺乏了解。在这里,我们在小鼠中采用高深度单细胞RNA测序(scRNA-seq)结合逆行追踪来鉴定DPA和MTN神经元的内在转录特征。我们的转录组分析揭示了具有细胞类型特异性基因富集的五种主要类型的DPA神经元,其中一些表现出独特的机械伤害感受特性,能够对牙齿中无害的机械刺激进行传递伤害感受。此外,我们发现MTN神经元内的细胞异质性可能有助于它们对咬肌纺锤体机械拉伸的反应。此外,DPA和MTN神经元代表了具有不同分子特征的感觉区室,其特征是各种离子通道、受体、神经肽和机械感受器。总之,我们的研究为DPA和MTN神经元在疼痛和本体感觉中的高度专业化机械感觉功能提供了新的生物学见解。
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引用次数: 0
Oral squamous cell carcinomas: state of the field and emerging directions. 口腔鳞状细胞癌:研究现状和发展方向。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-09-22 DOI: 10.1038/s41368-023-00249-w
Yunhan Tan, Zhihan Wang, Mengtong Xu, Bowen Li, Zhao Huang, Siyuan Qin, Edouard C Nice, Jing Tang, Canhua Huang

Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% of oral malignancies and impairs appearance, pronunciation, swallowing, and flavor perception. In 2020, 377,713 OSCC cases were reported globally. According to the Global Cancer Observatory (GCO), the incidence of OSCC will rise by approximately 40% by 2040, accompanied by a growth in mortality. Persistent exposure to various risk factors, including tobacco, alcohol, betel quid (BQ), and human papillomavirus (HPV), will lead to the development of oral potentially malignant disorders (OPMDs), which are oral mucosal lesions with an increased risk of developing into OSCC. Complex and multifactorial, the oncogenesis process involves genetic alteration, epigenetic modification, and a dysregulated tumor microenvironment. Although various therapeutic interventions, such as chemotherapy, radiation, immunotherapy, and nanomedicine, have been proposed to prevent or treat OSCC and OPMDs, understanding the mechanism of malignancies will facilitate the identification of therapeutic and prognostic factors, thereby improving the efficacy of treatment for OSCC patients. This review summarizes the mechanisms involved in OSCC. Moreover, the current therapeutic interventions and prognostic methods for OSCC and OPMDs are discussed to facilitate comprehension and provide several prospective outlooks for the fields.

口腔鳞状细胞癌(OSCC)发生在口腔粘膜上皮上。它约占口腔恶性肿瘤的90%,并损害外观、发音、吞咽和味觉。2020年,全球共报告377713例OSCC病例。根据全球癌症观察站(GCO)的数据,到2040年,OSCC的发病率将上升约40%,同时死亡率也将上升。持续暴露于各种风险因素,包括烟草、酒精、槟榔液(BQ)和人乳头瘤病毒(HPV),将导致口腔潜在恶性疾病(OPMD)的发展,这是一种口腔粘膜病变,发展为OSCC的风险增加。致癌过程复杂且多因素,涉及基因改变、表观遗传学修饰和失调的肿瘤微环境。尽管已经提出了各种治疗干预措施,如化疗、放疗、免疫疗法和纳米医学,以预防或治疗OSCC和OPMD,但了解恶性肿瘤的机制将有助于识别治疗和预后因素,从而提高OSCC患者的治疗效果。本文综述了OSCC的相关机制。此外,还讨论了目前OSCC和OPMD的治疗干预措施和预后方法,以促进理解,并为该领域提供一些前瞻性的前景。
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引用次数: 0
Porphyromonas gingivalis, a periodontal pathogen, impairs post-infarcted myocardium by inhibiting autophagosome-lysosome fusion. 牙龈卟啉单胞菌是一种牙周病原体,通过抑制自噬体-溶酶体融合来损害梗死后的心肌。
IF 14.9 1区 医学 Q1 Dentistry Pub Date : 2023-09-18 DOI: 10.1038/s41368-023-00251-2
Yuka Shiheido-Watanabe, Yasuhiro Maejima, Shun Nakagama, Qintao Fan, Natsuko Tamura, Tetsuo Sasano

While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), the underlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, including heart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment by periodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate the relationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes (NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagy inhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. This study also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomal sensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity than gingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wild-type P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-type P.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which are virulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms the strong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.

尽管先前的几项研究表明牙周病(PD)和心肌梗死(MI)之间存在联系,但其潜在机制尚不清楚。自噬是一种在包括心力衰竭在内的多种疾病中被激活的细胞质量控制过程,可被牙龈卟啉单胞菌(P.g.)抑制。然而,尚不确定牙周病原体的自噬损伤是否会刺激MI后心脏功能障碍的发展。因此,本研究旨在探讨PD与MI发展之间的关系,同时重点研究自噬的作用。新生大鼠心肌细胞(NRCMs)和MI模型小鼠接种野生型P.g.或银杏素缺乏型P.g.以评估P.g.对自噬的抑制作用。野生型P.g.-接种的NRCMs的细胞活力低于接种银杏素缺乏的P.g.。本研究还揭示了银杏素可以切割囊泡相关膜蛋白8(VAMP8),一种参与溶酶体敏感因子附着蛋白受体(SNARE)的蛋白质,位于第47赖氨酸残基,从而抑制自噬。野生型P.g.接种的MI模型小鼠更容易发生心脏破裂,其存活率和自噬活性低于银杏叶素缺乏的P.g.接种MI模型小鼠。用野生型P.g.接种转基因MI模型小鼠(VAMP8-K47A)后,与接种野生型P.g.的MI模型小鼠相比,它们表现出显著增加的自噬激活,这抑制了心脏破裂并提高了总生存率。这些发现表明,银杏蛋白酶是P.g.的毒力因子,通过裂解VAMP8和破坏自噬来损害梗死心肌。这项研究证实了PD和MI之间的强烈关联,并为自噬在这种关系中的潜在作用提供了新的见解。
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International Journal of Oral Science
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