Traditional Chinese medicine (TCM) compounds have recently garnered attention for the regulation of immune cell infiltration and the prevention and treatment of Alzheimer’s disease (AD). The Liuwei Dihuang Pill (LDP) has potential in this regard; however, its specific molecular mechanism currently remains unclear. Therefore, we adopted a bioinformatics approach to investigate the infiltration patterns of different types of immune cells in AD and explored the molecular mechanism of LDP intervention, with the aim of providing a new basis for improving the clinical immunotherapy of AD patients. We found that M1 macrophages showed significantly different degrees of infiltration between the hippocampal tissue samples of AD patients and healthy individuals. Four immune intersection targets of LDP in the treatment of AD were identified; they were enriched in 206 biological functions and 30 signaling pathways. Quercetin had the best docking effect with the core immune target PRKCB. Our findings suggest that infiltrated immune cells may influence the course of AD and that LDP can regulate immune cell infiltration through multi-component, multi-target, and multi-pathway approaches, providing a new research direction regarding AD immunotherapy.

ObjectiveTo investigate potential biomarkers for the early detection of cognitive impairment in patients with Wilson’s disease (WD), we developed a computer-assisted radiomics model to distinguish between WD and WD cognitive impairment.MethodsOverall, 136 T1-weighted MR images were retrieved from the First Affiliated Hospital of Anhui University of Chinese Medicine, including 77 from patients with WD and 59 from patients with WD cognitive impairment. The images were divided into training and test groups at a ratio of 70:30. The radiomic features of each T1-weighted image were extracted using 3D Slicer software. R software was used to establish clinical and radiomic models based on clinical characteristics and radiomic features, respectively. The receiver operating characteristic profiles of the three models were evaluated to assess their diagnostic accuracy and reliability in distinguishing between WD and WD cognitive impairment. We combined relevant neuropsychological test scores of prospective memory to construct an integrated predictive model and visual nomogram to effectively assess the risk of cognitive decline in patients with WD.ResultsThe area under the curve values for distinguishing WD and WD cognitive impairment for the clinical, radiomic, and integrated models were 0.863, 0.922, and 0.935 respectively, indicative of excellent performance. The nomogram based on the integrated model successfully differentiated between WD and WD cognitive impairment.ConclusionThe nomogram developed in the current study may assist clinicians in the early identification of cognitive impairment in patients with WD. Early intervention following such identification may help improve long-term prognosis and quality of life of these patients.

Background. Gandoufumu decoction (GDFMD) is a traditional Chinese medicine that has been widely used to treat Wilson’s disease (WD) liver damage patients. However, its specific molecular mechanism currently remains unclear. Autophagy as a key contributor to WD liver damage has been intensely researched in the recent years. Therefore, the aim of this present study is to explore the effect of GDFMD on autophagy in WD liver damage, and the final purpose is to provide scientific evidence for GDFMD treatment in WD liver damage. Methods. The molecular mechanisms and autophagy-related pathways of GDFMD in the treatment of WD liver damage were predicted using network pharmacology. Copper assay kit was used to determine copper content in serum. Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify serum levels of liver enzymes and oxidative stress-related indicators. Hematoxylin-eosin (HE), Masson, and Sirius red staining were used for the characterization of liver pathological changes. Transmission electron microscopy, immunofluorescence, and Western blot analyses were used to evaluate autophagy activity. The impact of the GDFMD on typical autophagy-related pathway (PI3K/Akt/mTOR pathway) molecules was also assessed via Western blot analysis. Results. GDFMD effectively attenuated serum liver enzymes, oxidative stress, autophagy, and degree of hepatic histopathological impairment and reduced serum copper content. Through network pharmacological approaches, PI3K/Akt/mTOR pathway was identified as the typical autophagy-related pathway of GDFMD in the treatment of WD liver damage. Treatment with GDFMD activated the PI3K/Akt/mTOR pathway, an effect that was able to be counteracted by LY294002, a PI3K antagonist or Rapa (rapamycin), an autophagy inducer. Conclusions. GDFMD imparted therapeutic effects on WD through autophagy suppression by acting through the PI3K/Akt/mTOR pathway.

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