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Dysregulation of a novel m6A regulator YWHAG is correlated with metastasis and poor prognosis in oral squamous cell carcinoma – A cross-sectional study
IF 2.2 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-09-12 DOI: 10.1016/j.archoralbio.2024.106090

Objective

This study aimed to investigate the role of a novel m6A and cell cycle regulator YWHAG in oral squamous cell carcinoma (OSCC) by analyzing its expression and functional implications.

Design

Tumor samples (n = 51) and adjacent non-tumor samples (n = 38) were collected from patients with OSCC, and cell lines were processed. YWHAG mRNA expression was assessed using quantitative reverse transcription PCR (RT-qPCR) analysis. Various tools, such as UALCAN, Protein-Atlas analysis, TIMER 2.0, and other in silico tools, were used to explore clinicopathological correlations, protein expression, immune cell infiltration, and functional associations of YWHAG.

Results

YWHAG mRNA and protein expression were significantly upregulated in OSCC tumor tissues and OSCC cell lines compared to non-tumor tissues and normal cells (p < 0.001). High YWHAG expression significantly correlated with advanced tumor stage, higher grade, lymph node metastasis, and poor prognosis (p < 0.05). Functional analysis revealed that YWHAG is associated with pathways involved in aggressive cancer progression. YWHAG expression positively correlated with its target gene CTTN expression, which was also upregulated in OSCC and associated with poor prognosis (p < 0.05).

Conclusions

Study findings indicate that YWHAG may contribute to the progression of OSCC and could be a potential therapeutic target or prognostic biomarker. Further investigation is necessary to understand the underlying mechanisms and assess the clinical implications of YWHAG dysregulation in OSCC.

本研究旨在通过分析新型 m6A 和细胞周期调节因子 YWHAG 的表达及其功能意义,研究其在口腔鳞状细胞癌(OSCC)中的作用。设计收集 OSCC 患者的肿瘤样本(n = 51)和邻近的非肿瘤样本(n = 38),并处理细胞系。采用定量反转录 PCR(RT-qPCR)分析评估 YWHAG mRNA 的表达。结果与非肿瘤组织和正常细胞相比,YWHAG mRNA和蛋白表达在OSCC肿瘤组织和OSCC细胞系中显著上调(p <0.001)。YWHAG的高表达与肿瘤晚期、分级、淋巴结转移和预后不良明显相关(p <0.05)。功能分析显示,YWHAG 与侵袭性癌症进展的相关通路有关。YWHAG的表达与其靶基因CTTN的表达呈正相关,CTTN在OSCC中也上调,且与预后不良相关(p <0.05)。要了解YWHAG在OSCC中失调的潜在机制并评估其临床意义,还需要进一步的研究。
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引用次数: 0
Impact of cathepsin K-induced proteoglycans degradation on dentin collagen cathepsin K 诱导的蛋白多糖降解对牙本质胶原蛋白的影响
IF 2.2 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-09-11 DOI: 10.1016/j.archoralbio.2024.106091

Objectives

This study aimed to investigate the effects of cathepsin K (catK) on proteoglycans (PGs) and the subsequent impacts on dentin collagen degradation.

Materials and Methods

Demineralized dentin samples were prepared and divided into the following groups: deionized water (DW), 0.1 U/mL chondroitinase ABC (C-ABC), and 1 μM odanacatib (ODN). Then, they were immersed for 48 h and then incubated in 1 mL of PBS (pH=5.5) at 37 °C for 5 d. Glycosaminoglycan (GAG) were examined to explore the degradation of PGs by catK. To determine the effect of catK-mediated PGs on dentin collagen degradation, hydroxyproline (HYP) assays, assessment of the degree of dentin crosslinking, and scanning electron microscopy (SEM) were assessed. Statistical analysis was conducted using one-way ANOVA followed by Tukey’s tests or Welch's ANOVA followed by Dunnett's tests at a significance level of 0.05.

Results

The production of GAG was significantly lower in the ODN group than in the DW group (P < 0.05), revealing that PG degradation was reduced in dentin after ODN treatment. Additionally, ODN treatment minimized the gaps in collagen fibers, improved fiber arrangement, and significantly increased the degree of collagen crosslinking, subsequently reducing the total amount of collagen fiber degradation in the dentin (P < 0.05).

Conclusions

CatK-mediated degradation of PGs negatively impacted the stability of collagen fibers, promoted gaps, led to a less organized arrangement of dentin collagen fibers, ultimately increasing collagen degradation.

材料与方法制备脱矿牙本质样品,将其分为以下几组:去离子水组(DW)、0.1 U/mL软骨素酶ABC组(C-ABC)和1 μM奥达那替布组(ODN)。然后,将它们浸泡 48 h,然后在 1 mL PBS(pH=5.5)中于 37 °C培养 5 d。为了确定 catK 介导的 PGs 对牙本质胶原降解的影响,还进行了羟脯氨酸(HYP)测定、牙本质交联程度评估和扫描电子显微镜(SEM)评估。统计分析采用单因素方差分析,然后进行 Tukey 检验或韦尔奇方差分析,然后进行 Dunnett 检验,显著性水平为 0.05。结果 ODN 组的 GAG 产量明显低于 DW 组(P <0.05),表明 ODN 处理后牙本质中的 PG 降解减少。此外,ODN 处理最大程度地减少了胶原纤维的间隙,改善了纤维排列,并显著提高了胶原交联度,从而减少了牙本质中胶原纤维降解的总量(P < 0.05)。
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引用次数: 0
Biochemical, pathohistological, radiographic and cardiological analysis reveals the possible association between apical periodontitis and cardiac function in diabetic rats 生化、病理组织学、放射学和心脏病学分析揭示了根尖牙周炎与糖尿病大鼠心脏功能之间可能存在的联系
IF 2.2 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-09-06 DOI: 10.1016/j.archoralbio.2024.106089

Objective

To evaluate the possible effects of apical periodontitis (AP) on cardiac function, structure, and oxidative stress (OS) in rats with diabetes mellitus type 2 (T2DM).

Design

Forty-eight (Wistar albino, male) rats were randomized into four groups: control healthy (CTRL), normoglycemic with AP (AP), T2DM, and T2DM with AP (T2DM+AP). T2DM was induced by streptozotocin and a high-fat diet. AP was induced by pulp exposure to the oral environment for 4 weeks and analyzed radiographically. In the blood samples insulin and glucose were established. In vivo, cardiac function was evaluated by echocardiography. Ex vivo cardiac function was assessed by the Langendorff technique. Heart tissue was analyzed pathophysiologically. OS was determined in cardiac tissue homogenate and coronary venous effluent, spectrophotometrically.

Results

Impaired glycoregulation was observed in the T2DM+AP group compared to the T2DM, AP, and CTRL groups. The T2DM+AP group was associated with disturbed echocardiography and cardiodynamic parameters. The levels of superoxide anion radical, nitrite, and index of lipid peroxidation were significantly increased, while the superoxide dismutase and catalase were significantly decreased in the T2DM+AP group compared to T2DM, AP, and CTRL groups. The radiographic AP area was significantly larger in the T2DM+AP compared to the AP group.

Conclusion

AP was associated with increased glucose levels, impaired cardiac function, structure, and OS in diabetic rats. Diabetes was related to an increased radiographic AP area. The study may be a starting point for further research to clarify the effects of AP on cardiac function in various models of systemic diseases.

目的 评估根尖牙周炎(AP)对 2 型糖尿病(T2DM)大鼠心脏功能、结构和氧化应激(OS)的可能影响。设计 将 48 只(Wistar albino,雄性)大鼠随机分为四组:健康对照组(CTRL)、正常血糖伴 AP 组(AP)、T2DM 组和 T2DM 伴 AP 组(T2DM+AP)。T2DM 由链脲佐菌素和高脂饮食诱发。诱发 AP 的方法是将牙髓暴露于口腔环境中 4 周,并进行放射学分析。在血液样本中检测胰岛素和葡萄糖。体内心脏功能通过超声心动图进行评估。体外心脏功能通过 Langendorff 技术进行评估。对心脏组织进行病理生理分析。结果与 T2DM、AP 和 CTRL 组相比,T2DM+AP 组的糖调节功能受损。T2DM+AP组的超声心动图和心脏动力学参数紊乱。与 T2DM 组、AP 组和 CTRL 组相比,T2DM+AP 组的超氧阴离子自由基、亚硝酸盐和脂质过氧化指数水平明显升高,而超氧化物歧化酶和过氧化氢酶水平明显降低。结论 AP 与糖尿病大鼠血糖水平升高、心脏功能受损、结构受损和操作系统受损有关。糖尿病与放射性 AP 面积增大有关。这项研究可作为进一步研究的起点,以明确 AP 在各种系统疾病模型中对心脏功能的影响。
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引用次数: 0
Enamel caries lesions, with and without initial cavitation, in relation to anatomical areas of the proximal surface in deciduous molars 与脱落磨牙近端表面解剖区域相关的釉质龋损(有无初始龋蚀)。
IF 2.2 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-08-31 DOI: 10.1016/j.archoralbio.2024.106081

Objective

proximal enamel caries lesions (PEC) are believed to initiate and progress to cavitation below the proximal contact area (PCA), but no evidence exists on the location of initial carious cavitation on the proximal surface with functional PCA. This study aimed to test the association of anatomical areas of the proximal surface with the severity of PEC and the frequency of cavitation in PEC in primary molars

Design

laboratory, observational, transversal study. Exfoliated primary molars (n = 33) with functional PCA (biofilm-free PCA surrounded by biofilm) had their proximal surfaces (one/tooth) divided anatomically into up to nine areas: 3 areas based on the occlusal/cervical PCA boundaries (areas I, II, and III; occluso-cervically) and 3 areas based on the bucco/lingual PCA boundaries (A, B, and C), with area IIB representing the PCA and area IIIB as the sub-PCA (below the PCA). PEC (ICDAS scores 1 and 2–3) and cavitation in PEC were quantified in all areas using stereomicroscopy and microCT. PEC volume was quantified in areas IIB and IIIB under microCT

Results

PEC severity increased occluso-cervically. PCA and sub-PCA presented different PEC severities (higher in sub-PCA) and similar PCE volumes, but the odds of carious cavitation were much higher (Odds ratio = 197.4; 95 % CI: 8.7/4480.7) in the PCA than in the sub-PCA (no cavitation).

Conclusion

PCA presented lower PEC severity and similar PEC volume compared to sub-PCA, but PCA concentrated all cavitations in PEC, supporting a new model for the pathogenesis of PEC.

目的:近端釉质龋损(PEC)被认为是在近端接触区(PCA)以下开始并发展到龋坏的,但没有证据表明近端表面初始龋坏的位置与功能性PCA有关。本研究旨在检验近端表面解剖区域与初级磨牙PEC严重程度和PEC龋蚀频率的关联性。对具有功能性 PCA(无生物膜的 PCA,周围有生物膜)的脱落初级磨牙(n = 33)的近端表面(一颗/颗)进行解剖学划分,最多可分为 9 个区域:其中 3 个区域以咬合/颈部 PCA 边界为基础(区域 I、II 和 III;咬合-颈部),3 个区域以颊面/舌面 PCA 边界为基础(A、B 和 C),区域 IIB 代表 PCA,区域 IIIB 为亚 PCA(位于 PCA 下方)。使用体视显微镜和显微 CT 对所有区域的 PEC(ICDAS 评分 1 和 2-3)和 PEC 中的空洞化进行量化。在显微 CT 下对 IIB 区和 IIIB 区的 PEC 容量进行了量化 结果:PEC 的严重程度在颈锁骨上有所增加。PCA和亚PCA的PEC严重程度不同(亚PCA更高),PCE体积相似,但PCA发生龋齿空洞化的几率(Odds ratio = 197.4; 95 % CI: 8.7/4480.7)远高于亚PCA(无空洞化):结论:与亚PCA相比,PCA的PEC严重程度较低,PEC体积相似,但PCA的所有龋损都集中在PEC,支持PEC发病机制的新模型。
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引用次数: 0
Spatio-temporal expression of Sox2+ progenitor cells regulates the regeneration of rat submandibular gland Sox2+祖细胞的时空表达调控大鼠下颌下腺的再生
IF 2.2 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-08-27 DOI: 10.1016/j.archoralbio.2024.106080

Objective

Sox2 plays crucial roles in tissues homeostasis and regeneration. However, there are lack of a comprehensive examination of Sox2 expression and its functional role in submandibular gland regeneration. Therefore, we aimed to elucidate the impact of Sox2 on submandibular gland regeneration.

Materials and Methods

A Sprague-Dawley rat submandibular gland duct ligation/de-ligation regeneration model was conducted in this study. Sox2-shRNA vectors were retro-ductally administered into the submandibular gland to establish a stable Sox2 knockdown model. Conventional histopathological and molecular biological methods were used to investigate phenotypic changes.

Results

The submandibular gland normalized completely 28 days after ligature removal (following 7 days of duct ligation). AQP5 expression gradually increased after ligation removal until returning to normal levels. In submandibular gland regeneration, Sox2 re-expressed and co-expressed with AQP5+ acinar cells, and Sox2 expression peaked on day 14, recovered to normal on day 28, reproducing the developmental pattern. Sox2 knockdown hindered gland regeneration and induced irreversible fibrosis. The AQP5 expression was significantly lower than the contemporaneous solely ligated group, while the blue collagen deposition and the Vimentin expression increased prominently. The expression of CD68, IL-1β, TNF-α and IL-17A increased significantly, and epithelial cells in the Sox2 knockdown group expressed higher levels of IL-17A.

Conclusions

These findings highlight Sox2 as a crucial regulator of the acinar cell lineage. Sox2+ progenitor cells are pivotal for acinar cell maintenance, which is indispensable for submandibular gland regeneration. Collectively, our findings may help develop targeted interventions for enhancing tissue repair and preventing irreversible fibrosis in salivary gland disorders.

目的Sox2在组织稳态和再生中发挥着关键作用。然而,目前还缺乏对 Sox2 表达及其在颌下腺再生中功能作用的全面研究。因此,我们旨在阐明 Sox2 对颌下腺再生的影响。将 Sox2-shRNA 载体经导管植入大鼠颌下腺,建立稳定的 Sox2 基因敲除模型。结果颌下腺在解除结扎28天后(结扎导管7天后)完全恢复正常。结扎解除后,AQP5 的表达逐渐增加,直至恢复到正常水平。在下颌下腺再生过程中,Sox2重新表达并与AQP5+尖突细胞共表达,Sox2表达在第14天达到峰值,第28天恢复正常,再现了发育模式。敲除 Sox2 会阻碍腺体再生并诱导不可逆的纤维化。AQP5的表达明显低于同期单纯结扎组,而蓝色胶原沉积和Vimentin的表达显著增加。CD68、IL-1β、TNF-α和IL-17A的表达明显增加,Sox2敲除组的上皮细胞表达更高水平的IL-17A。Sox2+祖细胞是维持尖体细胞的关键,而尖体细胞的维持是下颌下腺再生所不可或缺的。总之,我们的研究结果可能有助于开发有针对性的干预措施,以加强组织修复,防止唾液腺疾病发生不可逆转的纤维化。
{"title":"Spatio-temporal expression of Sox2+ progenitor cells regulates the regeneration of rat submandibular gland","authors":"","doi":"10.1016/j.archoralbio.2024.106080","DOIUrl":"10.1016/j.archoralbio.2024.106080","url":null,"abstract":"<div><h3>Objective</h3><p>Sox2 plays crucial roles in tissues homeostasis and regeneration. However, there are lack of a comprehensive examination of Sox2 expression and its functional role in submandibular gland regeneration. Therefore, we aimed to elucidate the impact of Sox2 on submandibular gland regeneration.</p></div><div><h3>Materials and Methods</h3><p>A Sprague-Dawley rat submandibular gland duct ligation/de-ligation regeneration model was conducted in this study. Sox2-shRNA vectors were retro-ductally administered into the submandibular gland to establish a stable Sox2 knockdown model. Conventional histopathological and molecular biological methods were used to investigate phenotypic changes.</p></div><div><h3>Results</h3><p>The submandibular gland normalized completely 28 days after ligature removal (following 7 days of duct ligation). AQP5 expression gradually increased after ligation removal until returning to normal levels. In submandibular gland regeneration, Sox2 re-expressed and co-expressed with AQP5<sup>+</sup> acinar cells, and Sox2 expression peaked on day 14, recovered to normal on day 28, reproducing the developmental pattern. Sox2 knockdown hindered gland regeneration and induced irreversible fibrosis. The AQP5 expression was significantly lower than the contemporaneous solely ligated group, while the blue collagen deposition and the Vimentin expression increased prominently. The expression of CD68, IL-1β, TNF-α and IL-17A increased significantly, and epithelial cells in the Sox2 knockdown group expressed higher levels of IL-17A.</p></div><div><h3>Conclusions</h3><p>These findings highlight Sox2 as a crucial regulator of the acinar cell lineage. Sox2<sup>+</sup> progenitor cells are pivotal for acinar cell maintenance, which is indispensable for submandibular gland regeneration. Collectively, our findings may help develop targeted interventions for enhancing tissue repair and preventing irreversible fibrosis in salivary gland disorders.</p></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Oral microbiota: Taxonomic composition and functional profile in caries-free and in caries-affected individuals – A systematic review 口腔微生物群:无龋人群和受龋影响人群的分类组成和功能特征 - 系统综述
IF 2.2 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-08-24 DOI: 10.1016/j.archoralbio.2024.106070

Objective

To compare the oral microbiota among caries-free (CF) with caries-affected (CA) individuals, both at taxonomic and at functional levels.

Design

This systematic review was conducted following PRISMA guidelines. A structured search was carried out in MEDLINE/PUBMED, Web of Science, EMBASE, LILACS, SciELO, Scopus and Google Scholar databases up to September, 2023. Observational studies, without any restriction on date of publication and using next-generation targeted or untargeted sequencing methods for identification of microbial communities were included. Qualitative synthesis was performed from all included studies.

Results

54 studies were included (43 cross-sectional; 11 cohort) comprising more than 3486 participants (at least 1666 CF and 1820 CA) whose saliva and/or dental plaque were used as clinical samples. Methodological quality was graded as “fair” for most of the studies. The abundance of 87 bacterial and 44 fungal genera were statistically different among CF and CA individuals. Atopobium spp., Capnocytophaga spp., Lactobacillus spp., Prevotella spp., Scardovia spp., Selenomonas spp. among others were frequently reported as being more abundant in CA individuals. Several functional patterns, such as lipids, carbohydrate, starch, sucrose, amino sugar metabolisms, among others, were identified as being specifically related to CF or to CA conditions.

Conclusion

In spite of the variability among the included studies and of the predominance of qualitative synthesis, groups of microorganisms as well as specific functional profiles coded by the assessed microbiota are differently abundant among caries-affected and caries-free individuals. These results need to be interpreted with caution considering the limitations inherent to each assessed primary study.

目的比较无龋(CF)和受龋影响(CA)个体的口腔微生物群,包括分类和功能两个层面。在截至 2023 年 9 月的 MEDLINE/PUBMED、Web of Science、EMBASE、LILACS、SciELO、Scopus 和 Google Scholar 数据库中进行了结构化检索。纳入的观察性研究不限发表日期,使用下一代定向或非定向测序方法识别微生物群落。结果共纳入 54 项研究(43 项横断面研究;11 项队列研究),超过 3486 名参与者(至少 1666 名 CF 患者和 1820 名 CA 患者)的唾液和/或牙菌斑被用作临床样本。大多数研究的方法学质量被评为 "一般"。87个细菌属和44个真菌属的丰度在CF和CA个体中存在统计学差异。常有报告称,CA 患者体内的 Atopobium 菌属、Capnocytophaga 菌属、Lactobacillus 菌属、Prevotella 菌属、Scardovia 菌属、Selenomonas 菌属等数量较多。结论尽管所纳入的研究之间存在差异,而且定性合成占主导地位,但在受龋影响和无龋的个体中,微生物群以及由评估微生物群编码的特定功能图谱的丰富程度各不相同。考虑到所评估的每项主要研究固有的局限性,在解释这些结果时需要谨慎。
{"title":"Oral microbiota: Taxonomic composition and functional profile in caries-free and in caries-affected individuals – A systematic review","authors":"","doi":"10.1016/j.archoralbio.2024.106070","DOIUrl":"10.1016/j.archoralbio.2024.106070","url":null,"abstract":"<div><h3>Objective</h3><p>To compare the oral microbiota among caries-free (CF) with caries-affected (CA) individuals, both at taxonomic and at functional levels.</p></div><div><h3>Design</h3><p>This systematic review was conducted following PRISMA guidelines. A structured search was carried out in MEDLINE/PUBMED, Web of Science, EMBASE, LILACS, SciELO, Scopus and Google Scholar databases up to September, 2023. Observational studies, without any restriction on date of publication and using next-generation targeted or untargeted sequencing methods for identification of microbial communities were included. Qualitative synthesis was performed from all included studies.</p></div><div><h3>Results</h3><p>54 studies were included (43 cross-sectional; 11 cohort) comprising more than 3486 participants (at least 1666 CF and 1820 CA) whose saliva and/or dental plaque were used as clinical samples. Methodological quality was graded as “fair” for most of the studies. The abundance of 87 bacterial and 44 fungal genera were statistically different among CF and CA individuals. <em>Atopobium</em> spp., <em>Capnocytophaga</em> spp., <em>Lactobacillus</em> spp., <em>Prevotella</em> spp., <em>Scardovia</em> spp., <em>Selenomonas</em> spp. among others were frequently reported as being more abundant in CA individuals. Several functional patterns, such as lipids, carbohydrate, starch, sucrose, amino sugar metabolisms, among others, were identified as being specifically related to CF or to CA conditions.</p></div><div><h3>Conclusion</h3><p>In spite of the variability among the included studies and of the predominance of qualitative synthesis, groups of microorganisms as well as specific functional profiles coded by the assessed microbiota are differently abundant among caries-affected and caries-free individuals. These results need to be interpreted with caution considering the limitations inherent to each assessed primary study.</p></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
CCKR signaling map, G-Protein bindings, hormonal regulation, and neural mechanisms may influence the osteogenic/cementogenic differentiation potential of hPDLSCs CCKR信号图谱、G蛋白结合、激素调控和神经机制可能会影响hPDLSCs的成骨/软骨分化潜能
IF 2.2 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-08-23 DOI: 10.1016/j.archoralbio.2024.106069

Objective

Periodontal regeneration poses challenges due to the periodontium's complexity, relying on mesenchymal cells from the periodontal ligament (hPDLSCs) to regenerate hard tissues like bone and cementum. While some hPDLSCs have high regeneration potential (HOP-hPDLSCs), most are low potential (LOP-hPDLSCs). This study analyzed hPDLSCs from a single donor to minimize inter-individual variability and focus on key differences in differentiation potentials.

Design

This study used RNA-seq, genomic databases, and bioinformatics tools to explore signaling pathways (SPs), biological processes (BPs), and molecular functions (MFs) guiding HOP cells to mineralized matrix production. It also investigated limitations of LOP cells and strategies for enhancing their osteo/cementogenesis.

Results

In basal conditions, HOP exhibited a multifunctional gene network with higher expression of genes related to osteo/cementogenesis, cell differentiation, immune modulation, stress response, and hormonal regulation. In contrast, LOP focused on steroid hormone biosynthesis and nucleic acid maintenance. During osteo/cementogenic induction, HOP showed strong modulation of genes related to angiogenesis, cell division, mesenchymal differentiation, and extracellular matrix production. LOP demonstrated neural synaptic-related processes and preserved cellular cytoskeleton integrity. CCKR map signaling and G-protein receptor bindings gained significance during osteo/cementogenesis in HOP-hPDLSCs. Both HOP and LOP shared common BPs related to gastrointestinal and reproductive system development.

Conclusion

The osteo/cementogenic differentiation of HOP cells may be regulated by CCKR signaling, G-protein bindings, and specific hormonal regulation. LOP cells seem committed to neural mechanisms. This study sheds light on hPDLSCs' complex characteristics, offering a deeper understanding of their differentiation potential for future periodontal regeneration research and therapies.

目标由于牙周的复杂性,牙周再生面临着挑战,需要依靠牙周韧带的间充质细胞(hPDLSCs)来再生骨和骨水泥等硬组织。虽然有些 hPDLSCs 具有高再生潜能(HOP-hPDLSCs),但大多数 hPDLSCs 的再生潜能较低(LOP-hPDLSCs)。本研究分析了来自单一供体的hPDLSCs,以尽量减少个体间的差异,并关注分化潜能的关键差异。本研究使用RNA-seq、基因组数据库和生物信息学工具来探索引导HOP细胞产生矿化基质的信号通路(SP)、生物过程(BP)和分子功能(MF)。结果在基础条件下,HOP表现出多功能基因网络,与骨/骨水泥生成、细胞分化、免疫调节、应激反应和激素调节相关的基因表达较高。相比之下,LOP侧重于类固醇激素的生物合成和核酸维护。在骨/软骨诱导过程中,HOP 对与血管生成、细胞分裂、间充质分化和细胞外基质生成有关的基因有很强的调节作用。LOP 显示了与神经突触相关的过程,并保持了细胞细胞骨架的完整性。CCKR图信号转导和G蛋白受体结合在HOP-hPDLSCs的骨/软骨生成过程中具有重要意义。结论 HOP细胞的骨/软骨形成分化可能受CCKR信号、G蛋白结合和特定激素调控。LOP 细胞似乎致力于神经机制。本研究揭示了 hPDLSCs 的复杂特性,为未来牙周再生研究和治疗提供了对其分化潜力的更深入了解。
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引用次数: 0
PRELP inhibits the progression of oral squamous cell carcinoma via inactivation of the NF-κB pathway PRELP 通过抑制 NF-κB 通路抑制口腔鳞状细胞癌的发展
IF 2.2 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-08-13 DOI: 10.1016/j.archoralbio.2024.106068

Objectives

The aim of this study was to investigate the role and molecular mechanism of proline/arginine-rich end leucine-rich repeat protein (PRELP), a secreted protein in extracellular matrix, in oral squamous cell carcinoma (OSCC) progression.

Design

PRELP expression in OSCC was analyzed in the Gene Set Enrichment (GSE) 138206, GSE37991, and GSE23558 datasets as well as cell lines. Also, PRELP expression and its relationship with prognosis and immune infiltration in head and neck squamous cell carcinoma (HNSCC) were confirmed by bioinformatics analysis. The proliferation, apoptosis, invasion, epithelial-to-mesenchymal transition (EMT) and NF-κB activation were detected after alteration of PRELP expression in OSCC cells using CCK-8, EdU, flow cytometry, Transwell, real-time PCR, immunofluorescence and Western blot. Additionally, an NF-κB inhibitor PDTC was used to confirm the regulation mechanism of PRELP.

Results

The expression of PRELP in OSCC tissues, cells and in HNSCC samples was low. HNSCC patients with higher PRELP expression was associated with longer overall survival. A positive correlation between PRELP expression and immune cell infiltration was found in HNSCC. Upregulation of PRELP inhibited, whereas PRELP silencing promoted, the proliferation, invasion and EMT of OSCC cells. Also, overexpression of PRELP promoted cell apoptosis. Mechanistically, PRELP suppressed p65 phosphorylation and nuclear translocation. And PDTC treatment partially reversed the influences of PRELP knockdown on the malignant behaviors in OSCC cells.

Conclusion

PRELP suppressed OSCC progression via inactivation of the NF-κB pathway. Targeting PRELP may be a potential approach for OSCC treatment.

设计通过基因组富集(GSE)138206、GSE37991和GSE23558数据集以及细胞系分析PRELP在OSCC中的表达。此外,还通过生物信息学分析证实了头颈部鳞状细胞癌(HNSCC)中 PRELP 的表达及其与预后和免疫浸润的关系。利用CCK-8、EdU、流式细胞术、Transwell、实时PCR、免疫荧光和Western blot检测了PRELP表达改变后OSCC细胞的增殖、凋亡、侵袭、上皮细胞向间质转化(EMT)和NF-κB活化。结果PRELP在OSCC组织、细胞和HNSCC样本中的表达量较低。PRELP表达较高的HNSCC患者总生存期较长。在 HNSCC 中发现 PRELP 表达与免疫细胞浸润呈正相关。PRELP 的上调抑制了 OSCC 细胞的增殖、侵袭和 EMT,而 PRELP 的沉默则促进了它们的增殖、侵袭和 EMT。此外,过表达 PRELP 还会促进细胞凋亡。从机理上讲,PRELP 可抑制 p65 磷酸化和核转位。结论 PRELP通过抑制NF-κB通路抑制OSCC的进展。以PRELP为靶点可能是治疗OSCC的一种潜在方法。
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引用次数: 0
Oral microbiome insights: Tracing acidic culprits in dental caries with functional metagenomics 洞察口腔微生物组:利用功能元基因组追踪龋齿的酸性元凶
IF 2.2 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-08-13 DOI: 10.1016/j.archoralbio.2024.106064

Objective

This study aimed to investigate the presence and abundance of acid-producing bacteria in dental caries samples using functional gene prediction techniques.

Design

A total of 24 dental caries samples were collected for analysis. DNA isolation was performed followed by shotgun metagenomic sequencing. Functional gene prediction techniques were used to identify enzymes responsible for acid production from primary metabolites. Enzymes responsible for converting primary metabolites into acids were identified from the KEGG database. Subsequently, 840 contigs were examined, and their genus and species were characterized.

Results

Analysis of the obtained data revealed 31 KEGG IDs corresponding to enzymes involved in the conversion of primary metabolites into acids. All 117 identified genera from the contig analysis were found to be part of the oral microbiome. In addition, A higher prevalence of acid-producing bacteria was noted in dental caries samples compared to earlier reports.

Conclusion

The study indicates the significant role of acid-producing bacteria in the initiation and progression of dental caries. The findings highlight the importance of microbial activity in the demineralization process of tooth enamel. Methods for preventing dental decay may be promising if specific measures are implemented to reduce the amount of acid produced by oral bacteria.

本研究旨在利用功能基因预测技术研究龋齿样本中产酸细菌的存在和丰度。对样本进行DNA分离,然后进行射枪元基因组测序。利用功能基因预测技术鉴定负责从初级代谢物中产酸的酶。从 KEGG 数据库中确定了负责将初级代谢物转化为酸的酶。结果分析获得的数据发现,有 31 个 KEGG ID 与参与将初级代谢物转化为酸的酶相对应。从序列分析中确定的所有 117 个属都是口腔微生物组的一部分。此外,与之前的报告相比,龋齿样本中产酸细菌的流行率更高。研究结果凸显了微生物活动在牙釉质脱矿过程中的重要性。如果采取具体措施减少口腔细菌产生的酸量,预防蛀牙的方法可能会大有可为。
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引用次数: 0
Testing the patterning cascade model of cusp development in Macaca fascicularis mandibular molars 测试猕猴下颌臼齿尖突发育的模式级联模型
IF 2.2 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2024-08-08 DOI: 10.1016/j.archoralbio.2024.106067

Objective

Molar crown configuration plays an important role in systematics, and functional and comparative morphology. In particular, the number of cusps on primate molars is often used to identify fossil species and infer their phylogenetic relationships. However, this variability deserves renewed consideration as a number of studies now highlight important developmental mechanisms that may be responsible for the presence of molar cusps in some mammalian taxa. Experimental studies of rodent molars suggest that cusps form under a morphodynamic, patterning cascade model of development (PCM) that involve the iterative formation of enamel knots. This model posits that the size, shape and location of the first-forming cusps determines the presence and positioning of later-forming cusps.

Design

Here we test whether variation in accessory cusp presence in 13 Macaca fascicularis mandibular second molars (M2s) is consistent with predictions of the PCM. Using micro-CT, we imaged these M2s and employed geometric morphometrics to examine whether shape variation in the enamel-dentine junction (EDJ) correlates with accessory cusp presence.

Results

We find that accessory cusp patterning in macaque M2s is broadly consistent with the PCM. Molars with accessory cusps were larger in size and possessed shorter relative cusp heights compared to molars without accessory cusps. Peripheral cusp formation was also associated with more centrally positioned primary cusps, as predicted by the PCM.

Conclusions

While these results demonstrate that a patterning cascade model is broadly appropriate for interpreting cusp variation in Macaca fascicularis molars, it does not explain all manifestations of accessory cusp expression in this sample.

目的臼齿齿冠构造在系统学、功能形态学和比较形态学中发挥着重要作用。特别是,灵长类臼齿上的尖齿数量经常被用来鉴定化石物种和推断其系统发育关系。然而,这种变异性值得重新考虑,因为现在的一些研究强调了一些哺乳动物类群中臼齿尖突存在的重要发育机制。对啮齿类臼齿的实验研究表明,臼齿尖突是在形态动力学、模式化级联发育模式(PCM)下形成的,其中涉及釉质结的迭代形成。设计在此,我们测试了 13 颗猕猴下颌第二臼齿(M2s)中附属尖突存在的变化是否与 PCM 的预测一致。我们使用显微 CT 对这些 M2 进行了成像,并采用几何形态计量学方法研究了釉齿交界处 (EDJ) 的形状变化是否与附属尖突的存在相关。与无附属尖突的磨牙相比,有附属尖突的磨牙尺寸更大,相对尖突高度更短。结论虽然这些结果表明,模式化级联模型大致适合解释猕猴臼齿尖突的变化,但它并不能解释该样本中附属尖突表达的所有表现形式。
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Archives of oral biology
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