Background Sialolithiasis or salivary gland stones are associated with high clinical morbidity. The advances in the treatment of sialolithiasis has been limited, however, by our understanding of their composition. More specifically, there is little information regarding the formation and composition of the protein matrix, the role of mineralogical deposition, or the contributions of cell epithelium and secretions from the salivary glands. A better understanding of these stone characteristics could pave the way for future non-invasive treatment strategies. Methods Twenty-nine high-quality ductal stone samples were analyzed. The preparation included successive washings to avoid contamination from saliva and blood. The sialoliths were macerated in liquid nitrogen and the maceration was subjected to a sequential, four-step, protein extraction. The four fractions were pooled together, and a standardized aliquot was subjected to tandem liquid chromatography mass spectrometry (LCMS). The data output was subjected to a basic descriptive statistical analysis for parametric confirmation and a subsequent G.O.-KEGG data base functional analysis and classification for biological interpretation. Results The LC-MS output detected 6934 proteins, 824 of which were unique for individual stones. An example of our sialolith protein data is available via ProteomeXchange with the identifier PXD012422. More important, the sialoliths averaged 53% homology with bone-forming proteins that served as a standard comparison, which favorably compared with 62% homology identified among all sialolith sample proteins. The non-homologous protein fraction had a highly variable protein identity. The G.O.-KEGG functional analysis indicated that extracellular exosomes are a primary cellular component in sialolithiasis. Light and electron microscopy also confirmed the presence of exosomal-like features and the presence of intracellular microcrystals. Conclusion Sialolith formation presents similarities with the hyperoxaluria that forms kidney stones, which suggests the possibility of a common origin. Further verification of a common origin could fundamentally change the way in which lithiasis is studied and treated.

中文翻译：

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唾液石蛋白的综合分析及其临床意义。


背景唾液腺结石或唾液腺结石与高临床发病率相关。然而，由于我们对其成分的了解，唾液结石治疗的进展受到限制。更具体地说，关于蛋白质基质的形成和组成、矿物沉积的作用或细胞上皮和唾液腺分泌物的贡献的信息很少。更好地了解这些结石特征可以为未来的非侵入性治疗策略铺平道路。方法对29份优质导管结石样品进行分析。准备工作包括连续清洗以避免唾液和血液污染。将唾液酸石在液氮中浸渍，并对浸渍物进行连续的四步蛋白质提取。将四个级分合并在一起，并对标准化等分试样进行串联液相色谱质谱分析 (LCMS)。数据输出经过基本描述性统计分析以进行参数确认，并随后进行 GO-KEGG 数据库功能分析和分类以进行生物学解释。结果 LC-MS 输出检测到 6934 个蛋白质，其中 824 个蛋白质是单个结石所独有的。我们的唾液酸蛋白数据示例可通过 ProteomeXchange 获取，标识符为 PXD012422。更重要的是，唾液石与作为标准比较的骨形成蛋白平均有 53% 的同源性，这比所有唾液石样品蛋白中鉴定出的 62% 同源性要好得多。非同源蛋白质部分具有高度可变的蛋白质特性。 GO-KEGG功能分析表明细胞外外泌体是唾液酸石症的主要细胞成分。光学和电子显微镜还证实了外泌体样特征的存在和细胞内微晶的存在。结论 唾液酸石的形成与形成肾结石的高草酸尿症具有相似性，这表明可能有共同的起源。进一步验证共同起源可能会从根本上改变结石病的研究和治疗方式。