Lijia Xu

Background: Motor progression in Parkinson's disease (PD) is highly heterogeneous, limiting prognosis and the efficiency of clinical trials that require accurate risk stratification. Traditional modeling approaches assume a single average trajectory and fail to capture meaningful divergence, whereas the biological determinants of trajectory‐defined subtypes remain unclear. Multivariate proteomic biomarkers may improve early identification of rapid progressors. Objectives: We aimed to (1) delineate distinct motor progression subtypes in early PD using longitudinal Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) III scores and (2) identify cerebrospinal fluid (CSF) proteomic signatures that discriminate rapid from slow progressors. Methods: We analyzed 5‐year longitudinal data from 396 Parkinson's Progression Markers Initiative (PPMI) participants with early PD. Motor progression trajectories were derived using latent class trajectory modeling (LCTM) of repeated MDS‐UPDRS III scores. CSF proteomics from 78 Olink samples were used for biomarker discovery, with least absolute shrinkage and selection operator (LASSO)–based feature selection followed by multivariable logistic regression. Validation was performed in 184 SOMAscan‐profiled samples. Results: LCTM identified distinct motor progression subtypes in early PD. Differential CSF protein expression across these trajectories highlighted candidate markers of rapid decline. A seven‐protein signature (CCL27, CXCL9, NEFL, SERPINE1, GH1, TYMP, KLK1) exhibited good discriminative performance for distinguishing rapid from slow progressors (area under the curve [AUC] = 0.908). In an independent cohort, the combined model showed consistent directional effects and achieved the highest accuracy (AUC = 0.796). Conclusions: Integrating trajectory modeling with CSF proteomics identified a concise seven‐protein signature associated with early PD progression, which showed reproducible patterns across two PPMI cohorts. This approach may support improved risk stratification in PD. © 2026 International Parkinson and Movement Disorder Society.

Background:Coreopsis tinctoria Nutt. (CT), an annual herb in the genus Coreopsis, is an important traditional medicine to be used for antidiabetes and antioxidation.Objective: The antioxidant compounds from CT may affect mitochondrial function and apoptosis, which in turn may affect related diseases. The aim of this study was to explore the potential molecular mechanism and new therapeutic opportunities of CT based on network pharmacology.Methods: A network pharmacology-based method, which combined data collection, drug-likeness filtering, target prediction, disease prediction, and network analysis, was used to decipher the potential targets and new therapeutic opportunities of CT. The potential molecular mechanism and pathway were explored through Gene Ontology (GO) and KEGG analyses. Then MPTP-induced SH-SY5Y cell model was applied to evaluate the neuroprotective effects and key targets.Results: There were 1,011 targets predicted for 110 compounds. Most targets were regulated by flavones, phenylpropanoids, and phenols and had synergistic effects on memory impairment, pancreatic neoplasm, fatty liver disease, and so on. The compounds–targets–diseases network identified TNF, PTGS2, VEGFA, BCL2, HIF1A, MMP9, PIK3CG, ALDH2, AKT1, and EGFR as key targets. The GO and KEGG analyses revealed that the cell death pathway, mitochondrial energy metabolism, and PI3K-AKT signal pathway were the main pathways. CT showed neuroprotective effects via regulating gene and protein expression levels of key targets in an in vitro model.Conclusion: CT had potential neuroprotective effects by targeting multiple targets related with apoptosis, which were affected by the BCL-2 and AKT signaling pathways. This study provided a theoretical basis for the research of neuroprotective effects of CT.

We aimed to ascertain the mechanism underlying the effects of acteoside (ACT) from Ligustrum robustum (Roxb.) Blume (Oleaceae) on lipid metabolism and synthesis. ACT, a water-soluble phenylpropanoid glycoside, is the most abundant and major active component of L. robustum; the leaves of L. robustum, known as kudingcha (bitter tea), have long been used in China as an herbal tea for weight loss. Recently, based on previous studies, our team reached a preliminary conclusion that phenylpropanoid glycosides from L. robustum most likely contribute substantially to reducing lipid levels, but the mechanism remains unclear. Here, we conducted an in silico screen of currently known phenylethanoid glycosides from L. robustum and attempted to explore the hypolipidemic mechanism of ACT, the representative component of phenylethanoid glycosides in L. robustum, using RNA-seq technology, quantitative real-time PCR (qPCR) and Western blotting. First, the screening results for six compounds were docked with 15 human protein targets, and 3 of 15 protein targets were related to cardiovascular diseases. Based on previous experimental data and docking results, we selected ACT, which exerted positive effects, for further study. We generated a lipid accumulation model using HepG2 cells treated with a high concentration of oleic acid and then extracted RNA from cells treated for 24 h with 50 μmol/L ACT. Subsequently, we performed a transcriptomic analysis of the RNA-seq results, which revealed a large number of differentially expressed genes. Finally, we randomly selected some genes and proteins for further validation using qPCR and Western blotting; the results agreed with the RNA-seq data and confirmed their reliability. In conclusion, our experiments proved that ACT from L. robustum alters lipid metabolism and synthesis by regulating the expression of multiple genes, including Scarb1, Scarb2, Srebf1, Dhcr7, Acat2, Hmgcr, Fdft1, and Lss, which are involved several pathways, such as the glycolytic, AMPK, and fatty acid degradation pathways.

Vine tea (VT), derived from Ampelopsis grossedentata (Hand.-Mazz.) W.T. Wang, is an alternative tea that has been consumed widely in south China for hundreds of years. It has been shown that drinking VT on a daily basis improves hyperlipidemia and hyperglycemia. However, little is known about the preventive functions of VT for metabolic dysregulation and the potential pathological mechanisms involved. This paper elucidates the preventive effects of VT on the dysregulation of lipid and glucose metabolism using rats maintained on a high-fat-diet (HFD) in an attempt to explain the potential mechanisms involved. Sprague Dawley (SD) rats were divided into five groups: a group given normal rat chow and water (control group); a group given an HFD and water (HFD group); a group given an HFD and Pioglitazone (PIO group), 5 mg /kg; and groups given an HFD and one of two doses of VT: 500 mg/L or 2000 mg/L. After 8 weeks, changes in food intake, tea consumption, body weight, serum and hepatic biochemical parameters were determined. Moreover, liver samples were isolated for pathology histology and liquid chromatography-mass spectrometry (LC-MS)-based metabolomic research. VT reduced the serum levels of glucose and total cholesterol, decreased glucose area under the curve in the insulin tolerance test and visibly impaired hepatic lipid accumulation. Metabolomics showed that VT treatment modulated the contents of metabolic intermediates linked to glucose metabolism (including gluconeogenesis and glycolysis), the TCA cycle, purine metabolism and amino acid metabolism. The current results demonstrate that VT may prevent metabolic impairments induced by the consumption of an HFD. These effects may be caused by improved energy-related metabolism (including gluconeogenesis, glycolysis and TCA cycle), purine metabolism and amino acid metabolism, and reduced lipid levels in the HFD-fed rats.

In the course of our study of bioactive natural products from Schisandra plants, we isolated a neolignan from an EtOAc extract of the stems of Schisandra propinqua (Wall.) Baill. The structure of the new compound was determined to be 4, 4‐di (4‐hydroxy‐3‐methoxyphenly)‐2, 3‐dimethylbutanol (compound 1) on the basis of ¹H‐ and ¹³C‐NMR spectra and 2D NMR methods. Eight known compounds, compounds 2‐9, were also isolated and identified, of which compounds 3, 4, 6 and 9 were isolated for the first time from this plant. In addition, compounds 1‐4 were evaluated for cytotoxicity by an 3‐(4,5‐dimethyl‐2 thiazoyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay. Compound 1 showed significant potential cytotoxic ability in the bioassay.(Managing editor: Wei Wang)