Abulhamael Ayman M, Bhandi Shilpa, Albar Nasreen H, Shaiban Amal S, Bavabeedu Shashit Shetty, Alzahrani Khalid J, Alzahrani Fuad M, Halawani Ibrahim F, Patil Shankargouda
Department of Endodontic, Faculty of Dentistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
College of Dental Medicine, Roseman University of Health Sciences, South Jordan, UT 84095, USA.
Microorganisms. 2023 Jul 6;11(7):1764. doi: 10.3390/microorganisms11071764.
is associated with endodontic pulpitis, causing damage to the dental pulp, leading to severe pain and a decline in quality of life. Regenerative pulp treatments using dental pulp stem cells (DPSCs) can be hindered by interactions between DPSCs and the infecting bacteria. The protein WNT family member 4 (Wnt4) plays a critical role in the differentiation of DPSCs and the regeneration of odontogenic tissue. However, the specific influence of on Wnt4 remains unclear. In this study, we employed a computational approach to investigate the underlying mechanisms through which -produced metabolites inhibit the Wnt4 protein, thereby diminishing the regenerative potential and therapeutic efficacy of odontogenic tissue. Among the metabolites examined, CHNOPS exhibited the strongest inhibitory effect on the Wnt4 protein, as evidenced by the lowest binding energy score of -6782 kcal/mol. Molecular dynamic simulation trajectories revealed that the binding of CHNOPS significantly altered the structural dynamics and stability of the Wnt4 protein. These alterations in protein trajectories may have implications for the molecular function of Wnt4 and its associated pathways. Overall, our findings shed light on the inhibitory impact of -produced metabolites on the Wnt4 protein. Further in vitro, in vivo, and clinical studies are necessary to validate and expand upon our findings.
与牙髓牙髓炎相关，会对牙髓造成损害，导致剧痛和生活质量下降。使用牙髓干细胞（DPSCs）进行的牙髓再生治疗可能会受到DPSCs与感染细菌之间相互作用的阻碍。蛋白质WNT家族成员4（Wnt4）在DPSCs的分化和牙源性组织的再生中起关键作用。然而，[此处原文缺失具体物质]对Wnt4的具体影响仍不清楚。在本研究中，我们采用了一种计算方法来研究[此处原文缺失具体物质]产生的代谢产物抑制Wnt4蛋白的潜在机制，从而降低牙源性组织的再生潜力和治疗效果。在所检测的代谢产物中，CHNOPS对Wnt4蛋白表现出最强的抑制作用，其最低结合能分数为-6782 kcal/mol证明了这一点。分子动力学模拟轨迹表明，CHNOPS的结合显著改变了Wnt4蛋白的结构动力学和稳定性。这些蛋白质轨迹的改变可能对Wnt4及其相关途径的分子功能有影响。总体而言，我们的研究结果揭示了[此处原文缺失具体物质]产生的代谢产物对Wnt4蛋白的抑制作用。需要进一步的体外、体内和临床研究来验证和扩展我们的研究结果。
