A comparative study of urinary levels of multiple metals and neurotransmitter correlations between GDM and T2DM populations.

OBJECTIVE: The pathogenesis of GDM and T2DM are closely related to various metals in vivo, and changes in the concentration of these metal exposures can lead to neuropathy through the DNA damage pathway caused by the accumulation of ROS. METHOD: Urine samples were analyzed for heavy metals and trace elements by ICP-MS, neurotransmitter metabolites by HPLC, 8-OH-dG by HPLC-MS and metabolomics by UPLC-MS. RESULT: Cd and Hg were risk factors for T2DM. There was a positive correlation between 8-OH-dG and neurotransmitter metabolites in both two populations. For GDM, the metabolite with the largest down-regulation effect was desloratadine and the largest up-regulation effect was D-glycine. That tyrosine and carbon metabolites were upregulated in the GDM population and downregulated in the T2DM population. CONCLUSION: The BMI, urinary Cd and Hg endo-exposure levels correlated with elevated blood glucose, and the latter may cause changes in the DNA damage marker 8-OH-dG in both study populations and trigger common responses to neurological alterations changes in the neurotransmitter. Tyrosine, carbonin metabolites, alanine, aspartate, and glutamate were signature metabolites that were altered in both study populations. These indicators and markers have clinical implications for monitoring and prevention of neurological injury in patients with GDM and T2DM.

Development of an in-line Raman analytical method for commercial-scale CHO cell culture process monitoring: Influence of measurement channels and batch number on model performance.

The mammalian cell culture process is a key step in commercial therapeutic protein production and needs to be monitored and controlled due to its complexity. Raman spectroscopy has been reported for cell culture process monitoring by analysis of many important parameters. However, studies on in-line Raman monitoring of the cell culture process were mainly conducted on small or pilot scale. Developing in-line Raman analytical methods for commercial-scale cell culture process monitoring is more challenging. In this study, an in-line Raman analytical method was developed for monitoring glucose, lactate, and viable cell density (VCD) in the Chinese hamster ovary (CHO) cell culture process during commercial production of biosimilar adalimumab (1500 L). The influence of different Raman measurement channels was considered to determine whether to merge data from different channels for model development. Raman calibration models were developed and optimized, with minimum root mean square error of prediction of 0.22 g L-1 for glucose in the range of 1.66-3.53 g L-1 , 0.08 g L-1 for lactate in the range of 0.15-1.19 g L-1 , 0.31 E6 cells mL-1 for VCD in the range of 0.96-5.68 E6 cells mL-1 on test sets. The developed analytical method can be used for cell culture process monitoring during manufacturing and meets the analytical purpose of this study. Further, the influence of the number of batches used for model calibration on model performance was also studied to determine how many batches are needed basically for method development. The proposed Raman analytical method development strategy and considerations will be useful for monitoring of similar bioprocesses.