Ferroptosis-related genes participate in the microglia-induced neuroinflammation of spinal cord injury via NF-κB signaling: evidence from integrated single-cell and spatial transcriptomic analysis.

Background: Ferroptosis and immune responses are critical pathological events in spinal cord injury (SCI), whereas relative molecular and cellular mechanisms remain unclear.

Methods: Micro-array datasets (GSE45006, GSE69334), RNA sequencing (RNA-seq) dataset (GSE151371), spatial transcriptome datasets (GSE214349, GSE184369), and single cell RNA sequencing (scRNA-seq) datasets (GSE162610, GSE226286) were available from the Gene Expression Omnibus (GEO) database. Through weighted gene co-expression network analysis and differential expression analysis in GSE45006, we identified differentially expressed time- and immune-related genes (DETIRGs) associated with chronic SCI and differentially expressed ferroptosis- and immune-related genes (DEFIRGs), which were validated in GSE151371.

A novel online calculator based on inflammation-related endotypes and clinical features to predict postoperative pulmonary infection in patients with cervical spinal cord injury.

Background: Postoperative pulmonary infection (POI) of patients with cervical spinal cord injury (CSCI) is highly heterogeneous, while the potential endotypes and related risk factors remain unclear.

Methods: A retrospective collection of 290 CSCI patients was conducted from January 2010 to July 2024 using 1:1 propensity score matching to compare POI (n = 145) and non-POI (n = 145) groups. We generated laboratory examination data from admission patients and identified endotypes using unsupervised consensus clustering and machine learning.

Tracing the evolving dynamics and research hotspots of spinal cord injury and surgical decompression from 1975 to 2024: a bibliometric analysis.

Background: Exploration of the benefits and timing of surgical decompression in spinal cord injury (SCI) has been a research hotspot. However, despite the higher volume and increasing emphasis on quality there remains no bibliometric view on SCI and surgical decompression. In this study, we aimed to perform bibliometric analysis to reveal the core countries, affiliations, journals, authors, and developmental trends in SCI and surgical decompression across the past 50 years.

Multiple signal-enhanced electrochemiluminescence aptamer sensors based on carboxylated ruthenium (II) complexes for acetamiprid detection.

Background: Rapid and sensitive detection for acetamiprid, a kind of widely used neonicotinoid insecticide, is very meaningful for the development of modern agriculture and the protection of human health. Highly stable electrochemiluminescence (ECL) materials are one of the key factors in ECL sensing technology. ECL materials prepared by porous materials (e.

Compensatory upregulation of MT2A alleviates neurogenic intermittent claudication through inhibiting activated p38 MAPK-mediated neuronal apoptosis.

Neurogenic intermittent claudication (NIC), a classic symptom of lumbar spinal stenosis (LSS), is associated with neuronal apoptosis. To explore the novel therapeutic target of NIC treatment, we constructed the rat model of NIC by cauda equina compression (CEC) method and collected dorsal root ganglion (DRG) tissues, a region responsible for sensory and motor function, for mRNA sequencing. Bioinformatic analysis of mRNA sequencing indicated that upregulated metallothionein 2A (MT2A), an apoptosis-regulating gene belonging to the metallothionein family, might participate in NIC progression.

TrkB/BDNF signaling pathway and its small molecular agonists in CNS injury.

As one of the most prevalent neurotrophic factors in the central nervous system (CNS), brain-derived neurotrophic factor (BDNF) plays a significant role in CNS injury by binding to its specific receptor Tropomyosin-related kinase receptor B (TrkB). The BDNF/TrkB signaling pathway is crucial for neuronal survival, structural changes, and plasticity. BDNF acts as an axonal growth and extension factor, a pro-survival factor, and a synaptic modulator in the CNS.

Reduced non-CpG methylation is a potential epigenetic target after spinal cord injury.

DNA methylation is a critical epigenetic regulator in the occurrence and development of diseases and is closely related to various functional responses in relation to spinal cord injury. To investigate the role of DNA methylation in spinal cord injury, we constructed a library with reduced-representation bisulfite sequencing data obtained at various time points (day 0-42) after spinal cord injury in mice. Global DNA methylation levels, specifically non-CpG (CHG and CHH) methylation levels, decreased modestly following spinal cord injury.

Spinal cord injury-activated C/EBPβ-AEP axis mediates cognitive impairment through APP C586/Tau N368 fragments spreading.

Spinal cord injury (SCI) leads to mental abnormalities such as dementia and depression; however, the molecular mechanism of SCI-induced dementia remains a matter of debate. Asparagine endopeptidase (AEP) mediated dementia by enhancing amyloid plaque and Tau hyperphosphorylation, indicating that it played an important role in neurodegeneration. Here we revealed that SCI stimulated AEP activation in mice with T9 contusion injury.

Treating Parkinson's Disease via Activation of BDNF/TrkB Signaling Pathways and Inhibition of Delta-Secretase.

Parkinson's disease (PD) is the second most common neurodegenerative disease with motor disorders as the key clinical features. BDNF/TrkB neurotrophic signalings are progressively reduced, whereas δ-secretase, a protease that cleaves α-synuclein (α-Syn) at N103 and promotes its aggregation and neurotoxicity, is gradually escalated in PD patient brains, associated with dopaminergic neuronal loss in the Substantia Nigra. Here, we show that stimulation of deficient BDNF/TrkB signalings with its small molecular agonist CF3CN displays the promising therapeutic effect, and blockade of δ-secretase with an optimal specific inhibitor #11A exhibits marked therapeutic effect, and combination of both demonstrates additive restorative efficacy in MPTP-induced human SNCA transgenic PD mice.

Temporal and spatial cellular and molecular pathological alterations with single-cell resolution in the adult spinal cord after injury.

Spinal cord injury (SCI) involves diverse injury responses in different cell types in a temporally and spatially specific manner. Here, using single-cell transcriptomic analyses combined with classic anatomical, behavioral, electrophysiological analyses, we report, with single-cell resolution, temporal molecular and cellular changes in crush-injured adult mouse spinal cord. Data revealed pathological changes of 12 different major cell types, three of which infiltrated into the spinal cord at distinct times post-injury.

Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells From Different Donors on Spinal Cord Injury in Mice.

Spinal cord injury (SCI) is caused by an external force, leading to severe dysfunction of the limbs below the injured segment. The inflammatory response plays a vital role in the prognosis of SCI. Human umbilical cord mesenchymal stem cell (hUCMSC) transplantation can promote repair of SCI by reducing the inflammatory response.

Neuronal ApoE4 stimulates C/EBPβ activation, promoting Alzheimer's disease pathology in a mouse model.

ApoE4 is a major genetic risk determinant for Alzheimer's disease (AD) and drives its pathogenesis via Aβ-dependent and -independent pathways. C/EBPβ, a proinflammatory cytokine-activated transcription factor, is upregulated in AD patients and increases cytokines and δ-secretase expression. Under physiological conditions, ApoE is mainly expressed in glial cells, but its neuronal expression is highly elevated under pathological stresses.

Neurotrophic signaling deficiency exacerbates environmental risks for Alzheimer's disease pathogenesis.

The molecular mechanism of Alzheimer's disease (AD) pathogenesis remains obscure. Life and/or environmental events, such as traumatic brain injury (TBI), high-fat diet (HFD), and chronic cerebral hypoperfusion (CCH), are proposed exogenous risk factors for AD. BDNF/TrkB, an essential neurotrophic signaling for synaptic plasticity and neuronal survival, are reduced in the aged brain and in AD patients.

Deep learning-based predictive identification of neural stem cell differentiation.

The differentiation of neural stem cells (NSCs) into neurons is proposed to be critical in devising potential cell-based therapeutic strategies for central nervous system (CNS) diseases, however, the determination and prediction of differentiation is complex and not yet clearly established, especially at the early stage. We hypothesize that deep learning could extract minutiae from large-scale datasets, and present a deep neural network model for predictable reliable identification of NSCs fate. Remarkably, using only bright field images without artificial labelling, our model is surprisingly effective at identifying the differentiated cell types, even as early as 1 day of culture.

A narrative review of the research progress and clinical application of platelet-rich plasma.

As a traditional treatment invented in the 1970s, the usage of platelet-rich plasma (PRP) has been reported constantly in many medical areas, such as tissue regeneration, wound healing, ligament repair, hair loss, and so on. In this review, we focus on the administration of PRP in musculoskeletal recovery. As a part of autogenous blood plasma, PRP's platelet concentration is above the baseline.

Delta-secretase triggers Alzheimer's disease pathologies in wild-type hAPP/hMAPT double transgenic mice.

Alzheimer's disease (AD) is the most common neurodegenerative disease with multifactorial pathologies including Aβ containing senile plaques and neurofibrillary tangles (NFT) consisted of aggregated Tau. Most of the AD patients are sporadic and the familial mutation hereditary patients are composed only 1% of all cases. However, the current AD mouse models employ mutated APP, PS1, or even Tau mutant, in order to display a portion of AD pathologies.

A Selective P2Y Purinergic Receptor Agonist 2-MesADP Enhances Locomotor Recovery after Acute Spinal Cord Injury.

Introduction: Spinal cord injury (SCI) causes most severe motor and sensory dysfunctions. In Chinese traditional medicine, the agonist of a purinergic receptor is believed to have a positive effect on SCIs, and 2-Methylthio-adenosine-5'-diphosphate (2-MesADP) is a selective agonist of the P2Y purinergic receptor.

Methods: To investigate its therapeutic function and molecular mechanism in SCI, transcriptome analysis associated with weighted gene co-expression network analysis (WGCNA) was carried out at various time points after T9 crush injury.

A mouse model of complete-crush transection spinal cord injury made by two operations.

Background: More and more studies have focused on the treatment of spinal cord injury (SCI) by tissue engineering, but there is still no ideal animal model that can genuinely and objectively simulate the real pathological process in clinical practice. Also, given the increasing availability and use of genetically modified animals in basic science research, it has become essential to develop clinically related models for SCI for use in mice.

Methods: Forty-eight C57BL/6 mice were divided into three groups (injured/sham/uninjured).

Intravenous delivery of microRNA-133b along with Argonaute-2 enhances spinal cord recovery following cervical contusion in mice.

Background Context: Acute spinal cord injury (SCI) is a devastating condition for which spine decompression and stabilization of injury remains the only therapy available in the clinical setup. However, fibrous scar formation during the healing process significantly impairs full recovery. MicroRNAs (miRs) are small noncoding RNAs that regulate gene expression by binding to target mRNA(s) and initiating translational repression or mRNA degradation.

C/EBPβ/δ-secretase signaling mediates Parkinson's disease pathogenesis via regulating transcription and proteolytic cleavage of α-synuclein and MAOB.

Parkinson's disease (PD) is characterized by dopaminergic neuronal loss and the presence of intra-neuronal Lewy body (LB) inclusions with aggregated α-synuclein (α-Syn) as the major component. MAOB, a crucial monoamine oxidase for dopamine metabolism, triggers oxidative stress in dopaminergic neurons and α-Syn aggregation. However, the key molecular mechanism that mediates PD pathogenesis remains elusive.

Traumatic brain injury triggers APP and Tau cleavage by delta-secretase, mediating Alzheimer's disease pathology.

Traumatic brain injury (TBI) is associated in some studies with clinical dementia, and neuropathological features, including amyloid plaque deposition and Tau neurofibrillary degeneration commonly identified in Alzheimer's disease (AD). However, the molecular mechanisms linking TBI to AD remain unclear. Here we show that TBI activates transcription factor CCAAT/Enhancer Binding Protein Beta (C/EBPβ), increasing delta-secretase (AEP) expression.

LncRNA MALAT1 inhibits hypoxia/reoxygenation-induced human umbilical vein endothelial cell injury via targeting the microRNA-320a/RAC1 axis.

Angiogenesis is believed to protect against hypoxia/reoxygenation (H/R)-induced cell injury. MALAT1 and microRNA-320a (miR-320a) are involved in cancer angiogenesis. To investigate the function of the MALAT1/miR-320a axis in H/R-induced cell injury, human umbilical vein endothelial cell (HUVEC) angiogenesis was detected using the Cell Counting Kit-8 (CCK-8), Transwell migration, cell adhesion and tube formation assays.