Lianmei Zhong

Peripheral nerve injuries tend to cause the proximal nerve unable to contact the corresponding target organ, resulting in sensory and motor dysfunction. The simple filling materials within nerve conduits are often inadequate for axonal ingrowth and directional regeneration. In this study, to enhance the guidance effect and achieve physiologically adaptive function, a 3D nanofibrous polyurethane (PU) scaffold with oriented microchannels was engineered using electrospinning and manual curling techniques. The electrospun fibrous membranes can be manually curled up into tubular structures with spiral and longitudinal multi-channels. The immunoregulatory and conductive properties were developed by being grafted gastrodin and aniline trimer (AT, 2.6 % and 5 %). Gastrodin stimulated proliferation of neural cells and expression of neuroblast-related genes. Electroactive AT produced an electrical signal in combination with electrical stimulation (ES) to accelerate the elongation and growth of Schwann cells (SCs) and neurite outgrowth of PC12 cells. The in vivo experiments revealed that the releasing gastrodin and electrical signals created prohealing microenvironment for alleviating inflammation and promoting vascularization. Of note, the topological structure provided well-organized internal support for the cells to spread, as well as the migration of SCs and the directional elongation of regenerating axons. The adaptive electroactivity of gastrodin-PU-AT5 % further ensured nerve signal transmission, ultimately promoted remyelination through upregulation of Rap1 and mTOR signaling pathways; thereby enhancing functional and structural regeneration. This scaffold design strategy will push forward the application of nerve conduits in long-distance peripheral nerve injury.

Background: Edaravone dexborneol, a novel neuroprotective agent with combined antioxidant and anti‐inflammatory properties, has demonstrated significant improvement in 90‐day functional outcomes for patients with acute ischemic stroke. This study aimed to evaluate the outcomes of edaravone dexborneol in patients with acute ischemic stroke with large infarct core. Methods: This prospective, multicenter, parallel‐group, real‐world cohort study was conducted between December 2022 and October 2023 across 72 centers in China. Participants were categorized into an exposed group (receiving edaravone dexborneol 37.5 mg/dose every 12 hours for 14 days) and an unexposed group (not receiving edaravone dexborneol). Propensity score matching (1:1) was used to balance baseline characteristics, and clinical outcomes were compared between the groups. The primary efficacy outcome was the proportion of patients achieving a modified Rankin Scale score of ≤2 at 90 days. Results: After matching, the 90‐day modified Rankin Scale ordinal shift was significantly better in the edaravone dexborneol group compared with the unexposed group (median: 2 [interquartile range, 1–4.5] versus 3 [interquartile range, 1–5]; unadjusted odds ratio [OR], 1.90 [95% CI, 1.04–3.46]; P =0.04). Patients in the edaravone dexborneol group had a higher rate of functional independence (58.8% versus 36.8%; unadjusted OR, 2.46 [95% CI, 1.23–4.90]; P =0.01) and a lower 90‐day mortality rate (11.8% versus 19.1%; unadjusted OR, 0.56 [95% CI, 0.22–1.46]; P =0.24). Conclusions: In patients with acute ischemic stroke with large infarct core, edaravone dexborneol improved the likelihood of achieving favorable functional outcomes at 90 days. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT05644223.

Background: Asparagine (Asn) metabolism is essential for maintaining cellular homeostasis and supporting neuronal energy demands. Recent studies have suggested its dysregulation may contribute to Alzheimer’s disease (AD) pathogenesis; however, the specific genes and regulatory mechanisms involved remain incompletely understood. Methods: Four publicly available microarray datasets (GSE5281, GSE29378, GSE36980, and GSE138260) were utilized to investigate genes with differential expression between control and AD samples. Asparagine metabolism-related genes (AMGs) were retrieved from the GeneCards database, and their intersection with DEGs yielded candidate asparagine metabolism-related differentially expressed genes (AMG-DEGs). Functional enrichment analysis (Gene Set Enrichment Analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes), protein–protein interaction (PPI) network analysis, and centrality scoring identified hub genes. Regulatory mechanisms were investigated through construction of competing endogenous RNA and transcription factor networks. Potential therapeutic compounds were predicted via drug–gene enrichment and evaluated using molecular docking simulations. Results: Thirty-nine AMG-DEGs were identified and found to be enriched in neurodevelopmental, synaptic transmission, and inflammatory signaling pathways. PPI analysis and centrality screening revealed seven hub genes ( HPRT1 , GAD2 , TUBB3 , GFAP , CD44 , CCL2 , and NFKBIA ). Regulatory network analysis highlighted specific miRNAs, long non-coding RNAs, and transcription factors involved in their modulation. Drug screening and docking identified Bathocuproine disulfonate, DL-Mevalonic acid, and Phenethyl isothiocyanate as promising compounds with strong binding affinities to hub proteins. Conclusion: This study comprehensively maps the dysregulation of asparagine metabolism in Alzheimer’s disease and reveals a set of hub genes and regulatory elements potentially involved in disease progression. The predicted therapeutic compounds provide a foundation for further experimental validation and may contribute to the development of novel metabolism-targeted strategies for AD treatment.

Neurological diseases present a wide range of conditions, intricate diagnosis and treatment processes, and complex prognostic considerations. Therefore, research focusing on the diagnosis and treatment of these diseases is crucial. Exosomal miRNAs are small RNA molecules enclosed in membrane vesicles, released by cells and known to play roles in the development of various neurological disorders. They also serve as specific biomarkers for these conditions. Drawing on extensive research on exosomal miRNAs in diseases like stroke, Alzheimer's, epilepsy, Parkinson's, and neuroregeneration, this paper provides a comprehensive review of the relationship between exosomal miRNAs and neurological diseases. We strive to offer current and detailed theoretical understandings to help with the diagnosis and treatment of these disorders.

Clinical use of small-diameter vascular grafts remains a challenging issue in neovessel regeneration in view of thrombosis and intimal hyperplasia. Developing a vascular graft with structure and function similar to those of the native vessels necessitates a major direction of vascular tissue regeneration. Thus, this study sought to design and fabricate a range of tri-phasic scaffolds (0, 2, and 5 wt% gastrodin-polyurethane (PU)) with spatiotemporally defined structure and gastrodin-release for regulating the highly coordinated processes in growth of the intima and media. While the small pores of inner layer guided infiltration of human umbilical vein endothelial cells (HUVECs), the bigger pores of medial layer could offer smooth muscle cell (SMC)-friendly habitat, and external fibers conferred adequate mechanical properties. Correspondingly, spatial distribution and differential regulation of key proteins in HUVECs and SMCs were mediated by hierarchical release of gastrodin, of which rapid release in inner layer elicited enhanced HUVEC proliferation and migration against those of the SMC via activated endothelial nitric oxide synthase (eNOS) and heat shock protein 70 (HSP70) signal. Of note, superior anti-coagulation was reflected in 2 wt% gastrodin-PU ex vivo extracorporeal blood circulation experiment. After in vivo implantation for 12 weeks, there was no formation of obvious thrombosis and intimal hyperplasia in 2 wt% gastrodin-PU. The scaffold maintained high patency and improved vascular remodeling, including the formation of thin endothelialization in lumen and dense extracellular matrix deposition in medial layer. Taken together, the results demonstrate the positive function of hierarchical releasing system that responded to tri-phasic structure, which not only suppressed intimal thickening but also tightly controlled tissue regeneration.

Introduction: Dimethyl fumarate (DMF) has shown potential for protection in various animal models of neurological diseases. However, the impact of DMF on changes in peripheral immune organs and the central nervous system (CNS) immune cell composition after ischemic stroke remains unclear. Methods: Eight-week-old C57BL/6J mice with photothrombosis (PT) ischemia and patients with acute ischemic stroke (AIS) were treated with DMF. TTC staining, flow cytometry, and immunofluorescence staining were used to evaluate the infarct volume and changes in immune cells in the periphery and the CNS. Results: DMF reduced the infarct volume on Day 1 after PT. DMF reduced the percentages of peripheral immune cells, such as neutrophils, dendritic cells, macrophages and monocytes, on Day 1, followed by NK cells on Day 3 and B cells on Day 7 after PT. In the CNS, DMF significantly reduced the percentage of monocytes in the brain on Day 3 after PT. In addition, DMF increased the number of microglia in the peri-infarct area and reduced the number of neurons in the peri-infarct area in the acute and subacute phases after PT. In AIS patients, B cells decreased in patients receiving alteplase in combination with DMF. Conclusion: DMF can change the immune environment of the periphery and the CNS, reduce infarct volume in the acute phase, promote the recruitment of microglia and preserve neurons in the peri-infarct area after ischemic stroke.

Objective: The purpose of this review is to identify the correlation between ICH and CSVD imaging markers under SMASH-U classification by searching and analyzing a large number of literatures in recent years, laying a theoretical foundation for future clinical research. At the same time, by collecting clinical data to evaluate patient prognosis, analyzing whether there are differences or supplements between clinical trial conclusions and previous theories, and ultimately guiding clinical diagnosis and treatment through the analysis of imaging biomarkers. Methods: In this review, by searching CNKI, Web of Science, PubMed, FMRS and other databases, the use of “spontaneous intracerebral hemorrhage”, “hypertensive hemorrhagic cerebral small vessel disease”, “cerebral small vessel disease imaging”, “Based cerebral small vessel diseases”, “SMASH the -u classification” and their Chinese equivalents for the main search term. We focused on reading and analyzing hundreds of relevant literatures in the last decade from August 2011 to April 2020, and also included some earlier literatures with conceptual data sources. After screening and ranking the degree of relevance to this study, sixty of them were cited for analysis and elaboration. Results: In patients with ICH, the number of cerebral microbleeds in lobes, basal ganglia, and the deep brain is positively correlated with ICH volume and independently correlated with neurological functional outcomes; white matter hyperintensity severity is positively correlated with ICH recurrence risk; multiple lacunar infarction independently predict the risk of ICH; severe brain atrophy is an independent risk factor for a poor prognosis in the long term in patients diagnosed with ICH; and the number of enlarged perivascular spaces is correlated with ICH recurrence. However, small subcortical infarct and ICH are the subject of few studies. Higher CSVD scores are independently associated with functional outcomes at 90 days in patients diagnosed with ICH.

Background: Parkinson’s disease (PD) is a well-known neurodegenerative disease that is usually caused by the progressive loss of dopamine neurons and the formation of Lewy vesicles. 3,4-Methylenedioxymethamphetamine (MDMA) has been reported to cause damage to human substantia nigra neurons and an increased risk of PD, but the exact molecular mechanisms need further investigation. Methods: MPTP- and MPP+-induced PD cells and animal models were treated with Nissl staining to assess neuronal damage in the substantia nigra (SN) area; immunohistochemistry to detect TH expression in the SN; TUNEL staining to detect apoptosis in the SN area; Western blotting to detect the inflammatory factors NF-κB, TNF-α, IL-6 and mitogen-activated protein kinase kinase kinase 3 (MEKK3); Griess assay for NO; RT‒qPCR for metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and miR-124 expression; Cell proliferation was assessed by CCK-8. Dual luciferase reporter genes were used to verify targeting relationships. Results: MDMA promoted MALAT1 expression, and knockdown of MALAT1 alleviated the MDMA-induced inhibition of SH-SY5Y cell proliferation, inflammation, NO release, SN neuronal injury, and TH expression inhibition. Both inhibition of miR-124 and overexpression of MEKK3 reversed the neuroprotective effects exhibited by knockdown of MALAT1. Conclusion: MDMA promotes MALAT1 expression and inhibits the targeted downregulation of MEKK3 by miR-124, resulting in upregulation of the expression of MEKK3 and finally jointly promoting PD progression.