Heliyon
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2024
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IF 3.4
Xu-Ying Li,Teng Xue,Hong Lai,Jing Dai,Fangda Peng,Fanxi Xu,Junge Zhu,Xian Li,Junya Hu,Wei Li,Raoli He,Lina Chen,Ying Chen,Chunguang Ding,Guoguang Zhao,Xianyang Chen,Qinyong Ye,Zhiheng Xu,Chaodong Wang
Introduction Multiple system atrophy (MSA) is a rapidly progressing neurodegenerative disorder. Although diverse biomarkers have been established for Parkinson's disease (PD), no widely accepted markers have been identified in MSA. Pyruvate and lactate are the end-product of glycolysis and crucial for brain metabolism. However, their correlation with MSA remains unclear. Moreover, it is elusive how lifestyles modify these metabolites. Methods To investigate the correlation and diagnostic value of plasma pyruvate and lactate levels in MSA and PD. Moreover, we explored how lifestyle-related metabolites interact with these metabolites in determining the disease risk. We assayed the 3 metabolites in pyruvate/lactate and 6 in the tea/coffee metabolic pathways by targeted mass spectrometry and evaluate their interactions and performance in diagnosis and differentiation between MSA and PD. Results We found that 7 metabolites were significantly different between MSA, PD and healthy controls (HCs). Particularly, pyruvate was increased in PD while significantly decreased in MSA patients. Moreover, the tea/coffee metabolites were negatively associated with the pyruvate level in HCs, but not in MSA and PD patients. Using machine-learning models, we showed that the combination of pyruvate and tea/coffee metabolites diagnosed MSA (AUC = 0.878) and PD (AUC = 0.833) with good performance. Additionally, pyruvate had good performance in distinguishing MSA from PD (AUC = 0.860), and the differentiation increased (AUC = 0.922) when combined with theanine and 1,3-dimethyluric acid. Conclusions This study demonstrates that pyruvate correlates reversely with MSA and PD, and may play distinct roles in their pathogenesis, which can be modified by lifestyle-related tea/coffee metabolites.
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DOI
PubMed
高影响因子
CRYSTAL GROWTH & DESIGN
·
2024
·
IF 3.2
Detao Li,Wenqian Chen,Limin Zhou,Li Xu,Feiqiang He,Jerry Y Y Heng,Hamza Shehzad,Jinbo Ouyang
Understanding drug cocrystal formation and its competitive mechanism is important for improving the physicochemical properties of drugs. In this article, the cocrystal formation of polyhydroxy natural products and their competitive mechanisms are discussed through experimental screening and theoretical calculations. The formation conditions and types of cocrystals were determined based on efficient screening experiments of polyhydroxy natural product cocrystals. To investigate the difficulty and stability of cocrystal formation, competitive cocrystal experiments of polyhydroxy natural products were carried out simultaneously. By simulation of the electrostatic potential surface of molecules and the Hirshfeld surface of crystals, the mode of hydrogen bonding within the crystals was determined. The strength of hydrogen bonding was assessed based on the intermolecular interactions and energy framework within the crystal structure. A “substitution model” was constructed based on experimental results and theoretical calculations, which is of great significance for the prediction and design of natural product cocrystals and provides a feasible solution for improving the physicochemical properties of drugs.
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DOI
高影响因子
SEPARATION AND PURIFICATION TECHNOLOGY
·
2024
·
IF 8.1
Detao Li,Zichen Ning,Zhuoshan Gong,Limin Zhou,Li Xu,Hamza Shehzad,Yan Zhao,Heng Jerry,Jinbo Ouyang
Design of natural product cocrystals and its formation mechanism are of great significance importance to the development of fields such as medicine, food, cosmetics, and agriculture. In this research, alkaloids (theophylline, theobromine) and polyhydroxy natural products (quercetin, resveratrol, naringin) were selected as the research subjects. Through competitive cocrystal experiments, the study explored the stability differences among different cocrystals. Based on theoretical calculations, the study determined the hydrogen bonds and π-π bonds within the crystals were identified. Combined with cocrystal structure analysis, we discussed the influence of hydrogen bonding networks and π-π stacking modes on cocrystal stability. According to these results, the study correlated the cocrystal stability with void level, establishing the void formula to predict the stability between different cocrystals. Additionally, it summarized the structural unit cell model of natural product cocrystals, revealing formation mechanism of cocrystals, and intuitively demonstrating effect of intermolecular interactions on stability of crystal. Finally, we proposed the stability law, establishing a close connection between intermolecular interactions, void level, and cocrystal stability, providing a theoretical basis for exploring relationship between cocrystal microstructure and stability.
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DOI
高影响因子
危险品化学品经营许可证（带存储）