Significant physiological changes occur in both the fetus and the mother during pregnancy. Urine proteins have been shown to reflect a wide range of physiological and pathological changes in the body. This study employed low-abundance protein-enriched magnetic nanobeads to conduct an in-depth analysis of the daily changes in urine proteins throughout the entire pregnancy of rats. Based on the 3455 identified urine proteins, fetal and maternal dynamic changes were observed in the pregnancy group compared to the control group, including blastocyst formation and cell division in the early stage of pregnancy. In addition, the morphogenesis- and development-related organs and tissues are significantly enriched at different stages of pregnancy. The 9th day after pregnancy is the stage when organ development is most concentrated, especially the nervous system and vasculature development. During the late stage of pregnancy, maternal-specific changes were observed, such as lactation. These results indicate that urine protein can reflect the fetal and maternal dynamic physiological alterations during pregnancy, which suggests the potential value of urine protein analysis in pregnancy health monitoring. It is emphasized that the analysis focuses on the daily variations in the urine proteins, as these daily changes are expected to reveal more dynamic and detailed information about the physiological processes during pregnancy.

Metformin is the first-line medication for treating type 2 diabetes mellitus, with more than 200 million patients taking it daily. Its effects are extensive and play a positive role in multiple areas. Can its effects and potential mechanisms be explored through the urine proteome? In this study, 166 differential proteins were identified following the administration of 150 mg/(kg·d) of metformin to rats for five consecutive days. These included complement component C6, pyruvate kinase, coagulation factor X, growth differentiation factor 15, carboxypeptidase A4, chymotrypsin-like elastase family member 1, and L-lactate dehydrogenase C chain. Several of these proteins have been reported to be directly affected by metformin or associated with its effects. Multiple biological pathways enriched by these differential proteins, or proteins containing differentially modified peptides, have been reported to be associated with metformin, such as the glutathione metabolic process, negative regulation of gluconeogenesis, and the renin–angiotensin system. Additionally, some significantly changed proteins and enriched biological pathways, not yet reported to be associated with metformin’s effects, may provide clues for exploring its potential mechanisms. In conclusion, the application of the urine proteome offers a comprehensive and systematic approach to exploring the effects of drugs, providing a new perspective on the study of metformin’s mechanisms.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes and there are currently no biomarkers for DPN in clinical practice. The objective of this study was to explore the diagnostic value of urine for diseases and discover potential markers. Urinary proteomics was used to analyze urine samples from patients with DPN and healthy individuals. Quantitative analysis of mass spectrometry data was performed using both group‐based and paired individual analysis strategies. A total of 2611 proteins were identified, of which 1759 were quantifiable, and 312 proteins showed significant differences (fold change > 2, adjusted p value < 0.01), with 239 decreased and 73 increased. A random grouping cross‐validation strategy was employed to evaluate the differentially expressed proteins, ensuring that the probability of random differences was less than 10%. Unsupervised clustering analysis of urinary proteomes among groups could distinguish most specimens. The most enriched GO biological processes were cytoplasmic translation, translation, exocytosis, chaperone‐mediated protein folding and immunoglobulin‐mediated immune response. The most significant KEGG signaling pathways were ribosome, coronavirus disease (COVID‐19), and metabolic pathways. Furthermore, some differentially expressed proteins were linked to the pathogenesis of diabetes, whereas others were associated with nerve damage. These molecules could serve as potential diagnostic and therapeutic biomarkers; some differential proteins have not yet been reported to be associated with DPN, providing clues for further research on their functions.