WTAP在肿瘤中作用的研究进展

N⁶-甲基腺嘌呤(N⁶-methyladenosine, m⁶A)是真核生物信使RNA中最普遍的一种修饰。Wilms肿瘤蛋白1相关蛋白(Wilms′tumor 1-associating protein, WTAP)作为m⁶A甲基化转移酶的调控亚基,与甲基转移样蛋白3(methyltransferase-like protein 3,METTL3)、甲基转移样蛋白14 (methyltransferase-like protein 14,METTL14)组成WMM复合物,催化m⁶A的产生。大量证据表明,WTAP可以通过调控RNA代谢,影响肿瘤的发生和进展,并与肿瘤的预后有着显著的相关性。本篇综述将关注WTAP的生物学功能和肿瘤中的作用,以及其作为肿瘤治疗潜在靶点的可行性。     

基于YTHDC2、IGF2BP2和HNRNPC的头颈部鳞状细胞癌N6-甲基腺苷风险模型构建及临床应用评估

目的 利用生物信息学技术构建头颈部鳞状细胞癌（HNSCC）N6-甲基腺苷（m⁶A）调节因子模型,进行预后及肿瘤免疫微环境评估。 方法 利用R语言对癌症基因组图谱（TCGA）数据库HNSCC患者进行m⁶A调节因子风险预后模型构建,然后对不同风险组进行差异基因分析、细胞类型富集分析和临床相关性分析。 结果 HNSCC中15个m⁶A调节因子表达异常,根据异常表达基因构建了HNSCC YTHDC2、IGF2BP2和HNRNPC三基因独立预后风险模型,其中高风险组免疫抑制相关因子及免疫细胞显著增多,抗肿瘤免疫相关因子及免疫细胞减少,呈现促肿瘤的免疫微环境。 结论 联合YTHDC2、IGF2BP2和HNRNPC的m⁶A调节因子风险预后模型可以有效评估HNSCC患者预后及肿瘤免疫浸润状态。     

铁调素及其与骨代谢的研究进展

铁调素(Hepcidin)是一类调节机体铁稳态的抗菌多肽,由HAMP基因编码,大量研究表明血清中铁的含量、骨形成蛋白(BMPs)、白介素-6(IL-6)及低氧诱导因子(HIF)等可调控铁调素的表达;最新研究表明其与骨代谢相关,铁调素可通过"铁调素-铁代谢-骨代谢"和"JAK/STAT"信号通路这两种途径影响骨代谢。该文就铁调素的生成机制及其在骨代谢中作用的相关研究进行综述。     

DNA甲基化在调节干细胞成骨分化中的作用

DNA甲基化和去甲基化是表观遗传学的重要机制之一,在细胞分化、增殖、衰老等方面具有重要的调控作用。干细胞在成骨分化过程中成骨特异性基因发生去甲基化进而表达上调,而与干细胞多能分化潜能相关的基因发生高甲基化进而表达抑制。DNA甲基化和去甲基化的动态变化和平衡,对于协调基因表达的时序性和抑制不和谐的分化表型具有重要作用,是干细胞成骨分化的重要保证。成骨分化中甲基化修饰机制的异常不仅会影响干细胞的正常成骨分化功能,并且与多种骨骼常见疾病的发生发展具有密切的关系。本文综述了干细胞成骨分化过程中受DNA甲基化修饰调控的相关基因和调控机制的新进展,以及DNA甲基化修饰异常可能导致的骨骼疾病。     

SIRT6在骨代谢中的作用研究进展

Sirtuin6(SIRT6)属于Sirtuin家族,具有去乙酰化酶和ADP-核糖基转移酶活性,在骨代谢、基因稳定、葡萄糖代谢、脂质代谢、炎性介质调控、肿瘤发生中发挥关键作用.本综述主要总结了SIRT6在骨代谢中的作用及其相关的分子信号通路.     

RNA腺嘌呤6-甲基化修饰调控骨髓间充质干细胞成骨向分化的研究进展

RNA腺嘌呤6-甲基化修饰是真核生物信使RNA和非编码RNA上最为常见的一种表观遗传修饰,对于真核生物多项生命活动的调控起着至关重要的作用。近来的研究发现,RNA腺嘌呤6-甲基化修饰在骨髓间充质干细胞的分化,尤其是成骨向分化上,扮演着十分重要的角色。本文通过对RNA腺嘌呤6-甲基化修饰调控骨髓间充质干细胞成骨向分化的相关研究加以总结,以期为后续基础研究以及临床应用提供新的思路。     

N6-腺苷酸甲基化修饰在口腔领域中的研究进展

N6-腺苷酸甲基化(m6A)是真核细胞中最丰富、分布最广泛的RNA内部修饰, 参与多种细胞基因表达调控与生物学过程。近年来, m6A修饰在口腔领域中的作用研究逐渐增多。研究显示, 多种m6A相关蛋白参与调控口腔鳞状细胞癌的发生发展及其对药物的耐受性;甲基化转移酶样蛋白3参与调控软骨细胞的凋亡和自噬、内皮祖细胞的血管生成和成骨能力、牙髓细胞的炎症反应、牙髓干细胞的分化和成骨过程、牙根的发育过程以及骨髓间充质干细胞的方向等;m6A修饰亦可能与牙周炎、口腔溃疡及口腔黏膜下纤维化的发病有关。这些研究为多种口腔疾病的发病机制和口腔骨组织修复及再生的研究提供了新思路。本文总结近年 m6A 修饰在口腔领域中的作用相关研究现状及进展, 旨在为进一步研究m6A在口腔领域中的作用和机制提供参考。     

哺乳动物雷帕霉素靶蛋白复合物1介导的自噬对骨代谢的调控

哺乳动物雷帕霉素靶蛋白复合物(mTORC)1是哺乳动物雷帕霉素靶蛋白形成的一种复合物,在细胞合成代谢过程中起重要作用,其参与调控的自噬作用近年来受到广泛关注。自噬是细胞降解损坏的蛋白质或细胞器并将其循环利用的过程。随着对mTORC1/自噬效应的研究逐渐深入,其在骨代谢方面的调控作用愈发凸显。本文就mTORC1介导的自噬通路在成骨细胞、破骨细胞等骨相关细胞方面的作用及其机制进行综述,为骨代谢的生物学机制和骨组织疾病的研究提供新思路。     

机械应力调控成骨细胞信号通路影响骨重塑的研究进展

<正>生理状态下，骨骼处于不断重建的连续过程，称为骨重塑。遗传、激素、营养、生物活性物质、机械力等都能影响此过程，其中机械应力是刺激骨形成的重要因素，比如促进骨骼成熟和重建等，其缺乏可导致骨代谢紊乱、骨量流失等^[1]。成骨细胞作为骨重塑中关键的效应细胞，可感受体内外力学刺激，并将力学信号转化为生物化学信号，参与骨形成的生理活动^[2]。机械应力能影响成骨细胞内不同信号通路而调节其增殖、分化等，从而调控骨重塑^[3]。本文对不同机械应力对成骨细胞信号通路调控的相关研究予以综述，以期为探究机械应力影响骨重塑的具体机制以及临床治疗骨相关疾病提供新思路。     

长链非编码RNA在干细胞成骨分化中作用机制的研究进展

在骨相关疾病治疗和骨组织工程中,干细胞作为成骨细胞的主要来源发挥着重要作用.长链非编码RNA(long non?coding RNA,lncRNA)可调控细胞周期、增殖代谢及谱系分化.随着高通量测序等研究技术的发展,lncRNA被发现可广泛参与干细胞的成骨调节.miRNA海绵作用是lncRNA调控成骨最经典的机制,近年...     

Specific acoustic impedance of enamel and dentine

Specific acoustic impedance (SPI) is a characteristic property of matter like elasticity and density to which it is related. A new method for determining longitudinal wave SPI has been employed on enamel and dentine of bovine incisors. The reflection ratio which is the ratio of the reflected pressure amplitude to that of the incident sound wave is measured directly. The specific acoustic impedance is determined from the reflection ratio when the SPI of the coupling medium is known. Since water with an SPI of 1.52 is used, the SPI for the dental materials is determinable.

Results from the reflection method compare favorably with those found by other investigators using different methods. A comparison in tabular form is included showing acoustic and elastic properties of enamel and dentine as reported by these investigators for human, bovine, and dog teeth.

Direct static measurement of Young's modulus for hard dental tissue generally yields lower values than obtained by ultrasonic techniques. Corresponding variations occur in the acoustic properties calculated from the directly measured elastic properties compared with the values found by acoustical tests. The writer has found the acoustical properties of bovine incisor enamel to be much like that of aluminum. For the specimens examined by the reflection ratio method, the specific acoustic impedance of bovine incisor enamel was 17.8 × 10⁶, kg/sec m², and the sonic velocity was 6030 m/sec. Corresponding values for bovine incisor dentine were 17.5 × 10⁶, kg/sec m² and 3400 m/sec.     

Bone metabolism and the receptor activator of nuclear factor-κB ligand (RANKL) pathway: a comprehensive review

The main metabolic function of bone is the homeostasis of calcium and phosphate. This is achieved through a balance of bone resorption and formation. To gain an understanding of bone turnover it is important to appreciate the different cells, regulatory steroids and hormones involved and how these have their actions. This article summarizes bone cells, normal bone metabolism, bone turnover, regulatory mechanisms and the clinical applications of these. The receptor activator of nuclear factor-kB, receptor activator of nuclear factor-kB ligand and osteoprotegerin (RANK/RANKL/OPG) cell signalling pathway is discussed in detail. Understanding these topics enhances knowledge of the pathological processes and diseases that result from failures of bone metabolism.     

125I放射性粒子植入联合TPF方案治疗无法手术的头颈部鳞癌

目的探讨¹²⁵I放射性粒子植入联合多西他赛-顺铂-氟尿嘧啶（TPF）方案同期放化疗治疗无法手术的头颈部鳞癌（HNSCC）的可行性及不良反应。 方法对23例初治疗的无法手术的HNSCC患者进行¹²⁵I放射性粒子植入治疗,同期给予多西他赛（75 mg/m²,第1天）、顺铂（75 mg/m²,第1天）和5-氟尿嘧啶（750 mg/m²,第2~5天）化疗方案治疗3个周期。 结果通过肿瘤体积变化情况和临床表现评价治疗标准,23例患者治疗总有效率达到78.3%。2年无进展生存率和总生存率分别为60.9%和52.2%,2例（8.7%）死于肿瘤复发,2例（8.7%）死于心血管疾病。主要的不良反应包括白细胞减少、恶心、呕吐、局部出血及放射性黏膜炎等,治疗过程未发生急性并发症与严重的放射性损伤。 结论¹²⁵I放射性粒子植入联合TPF治疗无法手术的中晚期HNSCC,是一种微创、有效、安全性高的治疗方案。     

外排子抑制剂对变异链球菌致龋毒力因子的影响

目的研究外排子抑制剂（EPI）对变异链球菌（S.mutans）及其生物学特性的调控作用。 方法通过溴化乙锭（EtBr）吸收和外排实验筛选变异链球菌EPI。检测变异链球菌外排子功能被抑制后,其药物敏感性、耐酸性、菌种间竞争能力和生物膜形成能力等生物学特性的改变。EPI筛选采用方差分析,生物学特性检测采用独立样本t检验进行比较,检验水准α = 0.05。 结果128 μg/ml利血平显著抑制变异链球菌的外排功能且不抑制其生长代谢,可作为变异链球菌的EPI。添加128 μg/ml利血平后,洗必泰对变异链球菌的最小抑菌浓度（MIC）降低75%至0.25 μg/ml;在pH = 3的环境中35 min后无活菌生长,与对照组相比差异有统计学意义;对戈登链球菌的抑菌圈减小[（8.81 ± 0.33）mm VS（14.25 ± 0.51）mm,P<0.0001];代表12和24 h生物膜生物量的A₅₇₅值分别从1.31 ± 0.01降低63.92%至0.47 ± 0.004（t = 227.267,P<0.0001）和1.94 ± 0.02降低73%至0.52 ± 0.003（t = 223.730,P<0.0001）;12 h生物膜总菌量与对照组（73.39 ± 2.56）μm³/μm²相比降低了24.73%,为（55.24 ± 3.20）μm³/μm²（t = 9.896,P<0.0001）。 结论EPI能显著提高变异链球菌对洗必泰的敏感性,降低其耐酸性、菌种间竞争和生物膜形成能力,提示外排子可作为潜在的防治龋病的新靶点,EPI有望成为临床龋病防治的一类新药物。     

The effect of ascorbic acid on the turnover of collagen in bone in tissue culture

Ascorbic acid is required for collagen synthesis but its role in other aspects of collagen metabolism is unclear. Neonatal mouse calvaria were incubated in tissue culture in the presence of 0·05 or 50·0 μg/ml ascorbic acid to determine the effect on bone collagen synthesis, crosslinking and degradation. H³-proline was added to the culture media to label the collagen newly synthesized in vitro with H³-hydroxyproline. Ascorbic acid increased the synthesis but descreased the degradation of the H³-hydroxyproline-labeled bone collagen. Ascorbate increased the specific activity (CPM H³-hyp/μg hyp) of the insoluble collagen, with no effect on the: acid-soluble collagen, indicating that the newly synthesized bone matrix was more highly crosslinked. On the other hand, the degradation of the preformed unlabeled collagen appeared to be increased. It was concluded that ascorbic acid increased bone collagen remodeling in vitro by favouring the the accumulation of newly synthesized bone collagen and the removal or degradation of the older preformed material.     

Indomethacin or flurbiprofen treatment of periodontitis in beagles: Effect on crevicular fluid arachidonic acid metabolites compared with effect on alveolar bone loss

The effect of two non-steroidal anti-inflammatory drugs, indomethacin and flurbiprofen, on the progression of alveolar bone loss and on the crevicular fluid (CF) levels of four arachidonic acid metabolites was compared in 16 beagle dogs over a 12-month period. Standardized radiographs were used to measure the rate of bone loss. Radioimmunoassay was used to measure CF levels of PGE₂, PGF_2α, TxB₂ and 6K-PGF_1α. Following a 6-month pretreatment baseline period, 5 dogs were dosed daily with 1.0 mg/kg indomethacin, 5 dogs were dosed daily with 0.02 mg/kg flurbiprofen, and 6 dogs were dosed with empty gelatin capsules for a 6-month period. With the administration of either indomethacin or flurbiprofen. the CF levels of PGE₂, PGF_2α, and TxB₂ were similarly significantly decreased; 6K-PGF_1α levels were not altered. Indomethacin and flurbiprofen did not have a similar effect on reducing the rate of alveolar bone loss. Flurbiprofen significantly decreased rate of bone loss from baseline whereas indomethacin did not. The data indicate that indomethacin and flurbiprofen inhibit CF arachidonic acid metabolite levels in a similar manner, but not rate of bone loss. The data suggest that flurbiprofen's striking effect on inhibiting rate of bone loss cannot be solely attributed to simple cyclooxygenase inhibition with a reduction in CF prostaglandin levels.     

The effect of ascorbic acid on the turnover of collagen in bone in tissue culture

Ascorbic acid is required for collagen synthesis but its role in other aspects of collagen metabolism is unclear. Neonatal mouse calvaria were incubated in tissue culture in the presence of 0·05 or 50·0 μg/ml ascorbic acid to determine the effect on bone collagen synthesis, crosslinking and degradation. H³-proline was added to the culture media to label the collagen newly synthesized in vitro with H³-hydroxyproline. Ascorbic acid increased the synthesis but descreased the degradation of the H³-hydroxyproline-labeled bone collagen. Ascorbate increased the specific activity (CPM H³-hyp/μg hyp) of the insoluble collagen, with no effect on the acid-soluble collagen, indicating that the newly synthesized bone matrix was more highly crosslinked. On the other hand, the degradation of the preformed unlabeled collagen appeared to be increased. It was concluded that ascorbic acid increased bone collagen remodeling in vitro by favouring the the accumulation of newly synthesized bone collagen and the removal or degradation of the older preformed material.     

Healing of extraction sockets in collagenase-2 (matrix metalloproteinase-8)-deficient mice

Matrix metalloproteinase-8 (MMP-8) participates in skin wound healing and inflammation. We hypothesized that MMP-8 plays a role in wound healing after tooth extraction and in periapical inflammation. Bone formation, collagen metabolism, and inflammation in tooth extraction socket and in periapical lesions were analyzed in wild-type mice and in MMP-8-deficient (MMP-8^−/−) mice. New trabecular bone area in the extraction sockets and in periapical lesions were similar in both groups. In extraction sockets significantly more type III procollagen was synthesized, and the neutrophil and MMP-9 levels were lower in MMP-8^−/− mice. The amount of Fas ligand, identified as a substrate for MMP-8, was lower in alveolar mucosa but higher in alveolar bone of MMP-8^−/− mice. These results indicate that MMP-8 can modulate inflammation and collagen metabolism of alveolar bone and mucosa.