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Mesenchymal stem cell (MSC) transplantation has been shown to represent a potential treatment for traumatic spinal cord injury (SCI). However, there are several obstacles that need to be overcome before MSCs can be considered for clinical application, such as failure of MSCs to reach the spinal cord lesion core and possible tumor formation. Recent studies have suggested that MSC treatment is beneficial owing to paracrine-secreted factors. Extracellular vesicles are considered to be some of the most valuable paracrine molecules. However, the therapeutic mechanism of extracellular vesicles on spinal cord injury has not been studied clearly. Therefore, our study investigated the effect of systemic administration of extracellular vesicles on the loss of motor function after SCI and examined the potential mechanisms underlying their effects. Disruption of the blood-spinal cord barrier (BSCB) is a crucial factor that can be detrimental to motor function recovery. Pericytes are an important component of the neurovascular unit, and play a pivotal role in maintaining the structural integrity of the BSCB. Our study demonstrated that administration of bone mesenchymal stem cell-derived extracellular vesicles (BMSC-EV) reduced brain cell death, enhanced neuronal survival and regeneration, and improved motor function compared with the administration of BMSC-EV free culture media (EV-free CM). Besides, the BSCB was attenuated and pericyte coverage was significantly decreased . Furthermore, we found that exosomes reduced pericyte migration via downregulation of NF-κB p65 signaling, with a consequent decrease in the permeability of the BSCB. In summary, we identified that extracellular vesicles treatment suppressed the migration of pericytes and further improved the integrity of the BSCB via NF-κB p65 signaling in pericytes. Our data suggest that extracellular vesicles may serve as a promising treatment strategy for SCI.

Neuroinflammation is initiated with an aberrant innate immune response in the central nervous system (CNS) and is involved in many neurological diseases. Inflammasomes are intracellular multiprotein complexes that can be used as platforms to induce the maturation and secretion of proinflammatory cytokines and pyroptosis, thus playing a pivotal role in neuroinflammation. Among the inflammasomes, the nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome is well-characterized and contributes to many neurological diseases, such as multiple sclerosis (MS), Alzheimer's disease (AD), and ischemic stroke. MS is a chronic autoimmune disease of the CNS, and its hallmarks include chronic inflammation, demyelination, and neurodegeneration. Studies have demonstrated a relationship between MS and the NLRP3 inflammasome. To date, the pathogenesis of MS is not fully understood, and clinical studies on novel therapies are still underway. Here, we review the activation mechanism of the NLRP3 inflammasome, its role in MS, and therapies targeting related molecules, which may be beneficial in MS.

Context: Hypoxic-ischemic encephalopathy (HIE) has a high morbidity and mortality rate. Resveratrol possesses numerous biological properties including antioxidant, anti-inflammatory and neuroprotective activities. Objective: The current experiment investigates the neuroprotective efficacy of resveratrol (RESV) against HIE by modulating Nrf2/HO-1 pathway in neonatal rats. Materials and methods: Seven-day-old pups (n = 48) were divided into four groups. Group-I rats receiving 2% DMSO saline (sham), group-II rats underwent unilateral carotid artery ligation and hypoxia (92% N 2 and 8% O 2 ) for 2.5 h (hypoxia-ischemia; HI), group-III and IV rats received 20 (RESV 20 + HI) or 40 mg/kg (RESV 40 + HI; group-IV) of RESV via intraperitoneal injection (ip), respectively, for 7 days prior to HI induction. Results: Pre-treatment with RESV (20 or 40) markedly reduced (p < 0.01) the cerebral oedema (86.23-71.26 or 65.24%), infarct area (33.85-19.81 or 14.30%), lipid peroxidation products, inflammatory markers [IL-1β 186-110 or 82; IL-6 255-146 or 103; TNF-α 310-204 or 137; NF-κB 205-115 or 91) p65 subunit] and significantly restored (p < 0.01) the antioxidative status by enhancing the activities of glutathione peroxidase (GPx) 5.22-6.49 or 7.78; catalase (CAT) 51-55 or 59, superoxide dismutase (SOD) 2.5-3.05 or 3.25; through marked upregulation (p < 0.01) of heme oxygenase 1 (HO-1) 0.65-0.69 or 0.73; and nuclear factor erythroid 2 related factor 2 (Nrf2) 0.73-0.86 or 0.91. Discussion and Conclusions: RESV displays its neurotherapeutic potential via upregulating the protein expression of Nrf2 and HO-1 signalling pathway and thereby attenuates oxidative stress and inflammatory response in HI-induced neonatal rats.

Increased extracellular free water (FW) is considered to provide better pathophysiological information than conventional diffusion tensor imaging (DTI) metrics. The cholinergic brain network is a key hub for cognitive function, and microstructural changes detected by free water imaging in this system may be associated with cognitive impairment in Alzheimer's disease (AD). However, the specific impact of FW changes in the cholinergic brain network on cognitive domains across the AD continuum and their diagnostic value remain unclear. Here, we investigated the basal forebrain cholinergic free water alterations based on free water-corrected diffusion tensor imaging in healthy controls (  = 36), amnestic mild cognitive impairment (aMCI;  = 31), the AD group (  = 33). The cholinergic basal forebrain subregions were divided into the Broca diagonal band (Ch1-3) and the Meynert basal nucleus (Ch4). The cognitive domains performance was measured using the Montreal Cognitive Assessment (MoCA). Additionally, we evaluated the diagnostic value of free water fraction (FWf) within the cholinergic system. FWf in the bilateral Ch1-3 and Ch4 regions increased with age, and was significantly higher in aMCI and AD (  < 0.001). In AD, the FWf within Ch4 was correlated with total MoCA score (  = -0.42,  = 0.015), especially with visual spatial/executive (  = -0.47,  = 0.006) and orientation deficits (  = -0.38,  = 0.029). No significant correlations were found in the aMCI group. ROC curve analysis showed that FWf within the cholinergic brain network had high diagnostic efficacy for AD versus HC (AUC = 0.958, 95% CI = 0.909-1.00), and moderate diagnostic efficacy for aMCI versus HC (AUC = 0.795, 95% CI = 0.685-0.905) and aMCI versus AD (AUC = 0.719, 95% CI = 0.589-0.850). FW imaging captures microstructural damage in the cholinergic brain network across the entire AD continuum. These changes occur early in aMCI but selectively affect domain-specific cognition in the later stages of AD, possibly through cholinergic network dysfunction. Our results highlight the potential of free water imaging as a biomarker for cognitive decline.

Background Neuroinflammation plays a significant role in the progression of frontotemporal dementia (FTD). However, the association between peripheral inflammatory factors and brain neurodegeneration is poorly understood. We aimed to examine changes in peripheral inflammatory markers in patients with behavioural variant FTD (bvFTD) and explore the potential association between peripheral inflammation and brain structure, metabolism, and clinical parameters. Methods Thirty-nine bvFTD patients and 40 healthy controls were enrolled and underwent assessment of plasma inflammatory factors, positron emission tomography/magnetic resonance imaging, and neuropsychological assessments. Group differences were tested using Student’s t test, Mann‒Whitney U test, or ANOVA. Partial correlation analysis and multivariable regression analysis were implemented using age and sex as covariates to explore the association between peripheral inflammatory markers, neuroimaging, and clinical measures. The false discovery rate was used to correct for the multiple correlation test. Results Plasma levels of six factors, including interleukin (IL)-2, IL-12p70, IL-17A, tumour necrosis superfamily member 13B (TNFSF/BAFF), TNFSF12 (TWEAK), and TNFRSF8 (sCD30), were increased in the bvFTD group. Five factors were significantly associated with central degeneration, including IL-2, IL-12p70, IL-17A, sCD30/TNFRSF8, and tumour necrosis factor (TNF)-α; the association between inflammation and brain atrophy was mainly distributed in frontal–limbic–striatal brain regions, whereas the association with brain metabolism was mainly in the frontal–temporal–limbic–striatal regions. BAFF/TNFSF13B, IL-4, IL-6, IL-17A and TNF-α were found to correlate with clinical measures. Conclusion Peripheral inflammation disturbance in patients with bvFTD participates in disease-specific pathophysiological mechanisms, which could be a promising target for diagnosis, treatment, and monitoring therapeutic efficacy.

Aim. The protection against ischemia/reperfusion injury mediated by remote limb ischemic postconditioning (RIPC) shows great clinical value in ischemic stroke therapy, but the particular mechanism of RIPC remains unclear. Methods. We carried out middle cerebral artery occlusion/reperfusion (MCAO/R) surgery on C57BL/6 male mice. RIPC was generated by 10-minute occlusion followed by the same period of reperfusion of the bilateral hind limb femoral artery and repeated for 3 cycles. Infarct size and neurological score were performed to assess stroke outcomes. Ly6Chi monocytes were quantified in the blood and brain by flow cytometry. Real-time PCR, ELISA, and immunofluorescence were utilized to detect phenotype of proinflammatory M1 and anti-inflammatory M2 microglia/macrophage. Nuclear factor κB (NF-κB) and peroxisome proliferator-activated receptor γ (PPARγ) levels were detected using Western blot. Results. At 24 and 72 h after MCAO, RIPC drastically attenuated infarct size and ameliorated the neurological deficits of mice and facilitated transmigration of Ly6Chi monocytes to the brain postischemia reperfusion. Furthermore, RIPC contributed to increased M2 and reduced M1 microglia/macrophage through inhibiting NF-κB and promoting PPARγ activation. Conclusion. Our results reveal pharmacological effect of RIPC in promoting microglia/macrophage transferring from M1 to M2 phenotype after MCAO/R in mice, which provides theoretical support for the therapeutic effect of RIPC in ischemic stroke.

Background Vascular dysfunction was recently reported to be involved in the pathophysiological process of neurodegenerative diseases, but its role in sporadic behavioral variant frontotemporal dementia (bvFTD) remains unclear. The aim of this study was to systematically explore vascular dysfunction, including changes in white matter hyperintensities (WMHs) and peripheral vascular markers in bvFTD. Methods Thirty-two patients with bvFTD who with no vascular risk factors were enrolled in this cross-sectional study and assessed using positron emission tomography/magnetic resonance (PET/MRI) imaging, peripheral plasma vascular/inflammation markers, and neuropsychological examinations. Group differences were tested using Student’s t -tests and Mann–Whitney U tests. A partial correlation analysis was implemented to explore the association between peripheral vascular markers, neuroimaging, and clinical measures. Results WMH was mainly distributed in anterior brain regions. All peripheral vascular factors including matrix metalloproteinases-1 (MMP-1), MMP-3, osteopontin, and pentraxin-3 were increased in the bvFTD group. WMH was associated with the peripheral vascular factor pentraxin-3. The plasma level of MMP-1 was negatively correlated with the gray matter metabolism of the frontal, temporal, insula, and basal ganglia brain regions. The WMHs in the frontal and limbic lobes were associated with plasma inflammation markers, disease severity, executive function, and behavior abnormality. Peripheral vascular markers were associated with the plasma inflammation markers. Conclusions WMHs and abnormalities in peripheral vascular markers were found in patients with bvFTD. These were found to be associated with the disease-specific pattern of neurodegeneration, indicating that vascular dysfunction may be involved in the pathogenesis of bvFTD. This warrants further confirmation by postmortem autopsy. Targeting the vascular pathway might be a promising approach for potential therapy.

Tanhuo formula (THF), a traditional Chinese medicinal formula, has been demonstrated to be effective in the clinical treatment of acute ischemic stroke (AIS). However, its active ingredients, potential targets, and molecular mechanisms remain unknown. Based on the validation of active ingredient concentrations, our study attempted to elucidate the possible mechanisms of THF based on network pharmacological analysis and experimental validation. Components of THF were screened using network pharmacological analysis, and a compound–target network and protein–protein interaction (PPI) network were constructed. In total, 42 bioactive compounds and 159 THF targets related to AIS were identified. The PPI network identified AKT1, TNF, IL6, IL1B, and CASP3 as key targets. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis demonstrated that the inflammation and apoptotic pathways were enriched by multiple targets. The main components of THF were identified via high-performance liquid chromatography. Subsequently, a validation experiment was conducted, and the expressions of GFAP, C3, TNF-α, and IL-6 were detected via immunofluorescence staining, confirming the inflammatory response at 30 min and 3 days post injury. Immunohistochemical staining for caspase-3 and TUNEL was also performed to assess apoptosis at the same time points. These results indicate that THF can effectively decrease neural cell apoptosis through the caspase-3 pathway and restrain excessive abnormal activation of astrocytes and the release of TNF-α and IL-6, which might be accompanied by the recovery of motor function. Thus, THF may serve as a promising therapeutic strategy for AIS through multiple targets, components, and pathways.

The modulation of the chemical microenvironment surrounding metal nanoparticles (NPs) is an effective means to enhance the selectivity and activity of catalytic reactions. Herein, a post‐synthetic modification strategy is developed to modulate the hydrophobic microenvironment of Ru nanoparticles encapsulated in a metal–organic framework (MOF), MIP‐206, namely Ru@MIP‐Fx (where x represents perfluoroalkyl chain lengths of 3, 5, 7, 11, and 15), in order to systematically explore the effect of the hydrophobic microenvironment on the electrocatalytic activity. The increase of perfluoroalkyl chain length can gradually enhance the hydrophobicity of the catalyst, which effectively suppresses the competitive hydrogen evolution reaction (HER). Moreover, the electrocatalytic production rate of ammonia and the corresponding Faraday efficiency display a volcano‐like pattern with increasing hydrophobicity, with Ru@MIP‐F7 showing the highest activity. Theoretical calculations and experiments jointly show that modification of perfluoroalkyl chains of different lengths on MIP‐206 modulates the electronic state of Ru nanoparticles and reduces the rate‐determining step for the formation of the key intermediate of N2H2*, leading to superior electrocatalytic performance. The Ru@MIP‐F7 catalyst is successfully synthesized by a post‐synthetic modification strategy. Strikingly, the electronic structure and hydrophobic microenvironmental modifications tailor the d‐band center position to optimize the adsorption of reaction intermediates, endowing the Ru@MIP‐F7 catalyst with superior activity in electrochemical nitrogen reduction reactions (Faraday efficiency: 40.94%, yield: 42.29 µg h−1 mgcat.−1), far superior to the corresponding counterparts.

In the context of the big data era, the study of the massive data accumulated in the information construction of higher vocational colleges and universities can provide convenience for the teaching and management of colleges and universities. By improving the K-means clustering algorithm and Apriori algorithm in big data mining technology, the article mines the English learning behaviors and laws of higher vocational English learners and explores the correlation between learners’ behavioral characteristics and teaching performance. Finally, through empirical testing, this paper proposes an optimization strategy for teaching content in higher vocational English education. In the comparative analysis of reading and writing pre-test and post-test scores between the experimental class and the control class, the pre-test score of reading comprehension of the students in the experimental class is 31.25, and the post-test score is 32.84, and the average score of reading comprehension has increased by 1.59, which can be obtained that the English reading comprehension of the students has been improved after teaching with the teaching content optimization strategy proposed in this paper.