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Background: Adult neurogenesis plays an important role in repairing damaged neurons and improving cognitive impairment in Alzheimer's disease (AD). B. Papyrifera (L.) L'Hér. ex Vent. fruits (BL), a traditional Chinese medicine for tonifying the kidney, has been reported to improve cognitive function in AD mice, but the underlying mechanisms have not been clearly illuminated. This study aimed to provide an overview of the differential compounds in the brain of APP/PS1 mice after BL water extract (BLWE) treatment through metabolomics technology and to elucidate whether the therapeutic effect and mechanism are through the enhancement of neurogenesis. Methods: APP/PS1 transgenic mice were treated with different doses of BLWE. After 6 weeks of intragastric injection, the therapeutic effects of BLWE on APP/PS1 transgenic mice were determined by the Morris water maze test, immunohistochemistry, hematoxylin & eosin and Nissl staining, enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Subsequently, metabolomics technology was used to analyze the regulatory effect of BLWE on differential compounds in the brain of APP/PS1 mice, and on this basis, its molecular mechanism of BLWE was screened. Finally, the protein expression of the Wnt/ß-catenin signaling pathway was detected by Western blotting. Results: After BLWE treatment, the learning and memory function of APP/PS1 mice were significantly improved, which was related to the increase in the number of Nestin+/BrdU+ and NeuN+/BrdU+ cells, and the decrease in the number of apoptotic cells in the hippocampus. BLWE treatment could also up-regulate the expression of synapse-associated proteins. Moreover, BLWE could modulate endogenous metabolic compounds in the brains of AD mice, including N-acetyl-aspartate, glutamine, etc. Furthermore, BLWE inhibited the phosphorylation of Tyr216-GSK-3ß and ß-catenin protein while increased CyclinD1 protein expression. Conclusion: We demonstrated that BLWE can enhance neural stem cells proliferation and improve neurogenesis, thereby efficiently repairing damaged neurons in the hippocampus and ameliorating cognitive impairment in APP/PS1 transgenic mice. The mechanism is at least partly through activating the Wnt/ß-catenin signaling pathway.
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INTRODUCTION: Focal lesion sites can predict the language function of patients with aphasia during the subacute or chronic phases. However, the relationship between focal lesion sites and language deficits in the acute phase remains unclear. Therefore, our study aimed to investigate the relationship between focal lesion sites and fluency, auditory comprehension, repetition and naming deficits in patients with acute aphasia to further understand the pathophysiological mechanism of aphasia. MATERIAL AND METHODS: We included a total of 52 patients with acute aphasia who had their first-ever stroke between June 2018 and June 2021 to investigate the association between focal lesion sites and fluency, auditory comprehension, repetition and naming deficits. Language function was assessed by the Western Aphasia Battery scale within one month of onset. The lesion sites were independently assessed by three professional speech and language pathologists according to the main sulcus of the brain within 1-2 days after stroke. RESULTS: Lesions involving the superior temporal gyrus, middle frontal gyrus, inferior frontal gyrus, precentral gyrus, postcentral gyrus, supramarginal gyrus, angular gyrus and insula were significantly associated with low fluency. Lesions involving the superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, middle frontal gyrus, inferior frontal gyrus, supramarginal gyrus and angular gyrus significantly resulted in auditory comprehension impairment. Lesions involving the superior temporal gyrus, middle temporal gyrus, middle frontal gyrus, inferior frontal gyrus, precentral gyrus, postcentral gyrus, supramarginal gyrus, angular gyrus and insula significantly resulted in repetition and naming deficits. CONCLUSIONS: Our study suggests that focal lesion sites could lead to different language function impairments in the acute phase of post-stroke aphasia, which adds to our understanding of speech pathology and provides a direction for future research and treatment.