O-demethyl galantamine alters protein expression in cerebellum of 5xFAD mice.

Background/aim: Alzheimer's disease (AD), one of the most common health issues, is characterized by memory loss, severe behavioral disorders, and eventually death. Despite many studies, there are still no drugs that can treat AD or stop it from progressing. Previous in vitro tests showed that O-demethyl galantamine (ODG) might have therapeutic potential owing to its 10 times higher acetylcholinesterase inhibitory activity than galantamine (GAL). Materials and methods: We aimed to assess the effect of ODG at the molecular level in a 12-month-old 5xFAD Alzheimer's mouse model. To this end, following the administrations of ODG and GAL (used as a positive control), protein alterations were investigated in the cortex, hippocampus, and cerebellum regions of the brain. Surprisingly, GAL altered proteins prominently in the cortex, while ODG exclusively exerted its effect on the cerebellum. Results: GNB1, GNB2, NDUFS6, PAK2, and RhoA proteins were identified as the top 5 hub proteins in the cerebellum of ODG-treated mice. Reregulation of these proteins through Ras signaling and retrograde endocannabinoid signaling pathways, which were found to be enriched, might contribute to reversing AD-induced molecular changes. Conclusion: We suggest that, since it targets specifically the cerebellum, ODG may be further evaluated for combination therapies for AD.

Longitudinal non-targeted metabolomic profiling of urine samples for monitoring of kidney transplantation patients.

The assessment of kidney function within the first year following transplantation is crucial for predicting long-term graft survival. This study aimed to develop a robust and accurate model using metabolite profiles to predict early long-term outcomes in patient groups at the highest risk of early graft loss. A group of 61 kidney transplant recipients underwent thorough monitoring during a one-year follow-up period, which included a one-week hospital stay and follow-up assessments at three and six months. Based on their 12-month follow-up serum creatinine levels: Group 2 had levels exceeding 1.5 mg/dl, while Group 1 had levels below 1.5 mg/dl. Metabolites were detected by mass spectrometer and first pre-processed. Univariate and multivariate statistical analyses were employed to identify significant differences between the two groups. Nineteen metabolites were found to differ significantly in the 1st week, and seventeen metabolites in the 3rd month (adjusted p-value < 0.05, quality control (QC) < 30, a fold change (FC) > 1.1 or a FC < 0.91, Variable Influence on Projection (VIP) > 1). However, no significant differences were observed in the 6th month. These distinctive metabolites mainly belonged to lipid, fatty acid, and amino acid categories. Ten models were constructed using a backward conditional approach, with the best performance seen in model 5 for Group 2 at the 1st-week mark (AUC 0.900) and model 3 at the 3rd-month mark (AUC 0.924). In conclusion, the models developed in the early stages may offer potential benefits in the management of kidney transplant patients.