Histopathological evaluation of the lungs in experimental autoimmune encephalomyelitis.

IMPORTANCE: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis characterized by inflammation within the central nervous system. However, inflammation in non-neuronal tissues, including the lungs, has not been fully evaluated. OBJECTIVE: This study evaluated the inflammatory response in lungs of EAE mice by immunohistochemistry and histochemistry. METHODS: Eight adult C57BL/6 mice were injected with myelin oligodendrocyte glycoprotein35-55 to induce the EAE. Lungs and spinal cords were sampled from the experimental mice at the time of sacrifice and used for the western blotting, histochemistry, and immunohistochemistry. RESULTS: Histopathological examination revealed inflammatory lesions in the lungs of EAE mice, characterized by infiltration of myeloperoxidase (MPO)- and galectin-3-positive cells, as determined by immunohistochemistry. Increased numbers of collagen fibers in the lungs of EAE mice were confirmed by histopathological analysis. Western blotting revealed significantly elevated level of osteopontin (OPN), cluster of differentiation 44 (CD44), MPO and galectin-3 in the lungs of EAE mice compared with normal controls (p < 0.05). Immunohistochemical analysis revealed both OPN and CD44 in ionized calcium-binding adapter molecule 1-positive macrophages within the lungs of EAE mice. CONCLUSIONS AND RELEVANCE: Taken together, these findings suggest that the increased OPN level in lungs of EAE mice led to inflammation; concurrent increases in proinflammatory factors (OPN and galectin-3) caused pulmonary impairment.

Identifying candidate genes associated with hippocampal dysfunction in a hemiparkinsonian rat model by transcriptomic profiling.

Parkinson's disease (PD) often results in hippocampal dysfunction, which leads to cognitive and emotional challenges and synaptic irregularities. This study attempted to assess behavioral anomalies and identify differentially expressed genes (DEGs) within the hippocampus of a hemiparkinsonian rat model to potentially uncover novel genetic candidates linked to hippocampal dysfunction. Striatal 6-hydroxydopamine (6-OHDA) infusions were performed unilaterally in the brains of adult SD rats, while dopaminergic impairments were verified in rats with 6-OHDA-lesioned striata. RNA sequencing and gene expression analysis unveiled 1018 DEGs in the ipsilateral rat hippocampus following 6-OHDA infusion: 631 genes exhibited upregulation, while 387 genes were downregulated (with FDR-adjusted p-value < 0.05 and absolute fold-change > 1.5). Gene ontology analysis of DEGs indicated that alterations in the hippocampi of 6-OHDA-lesioned rats were primarily associated with synaptic signaling, axon development, behavior, postsynaptic membrane, synaptic membrane, neurotransmitter receptor activity, and peptide receptor activity. The Kyoto Encyclopedia of Genes and Genomes analysis of DEGs demonstrated significant enrichment of the neuroactive ligand-receptor interaction, calcium signaling pathway, cAMP signaling pathway, axon guidance, and notch signaling pathway in rat hippocampi that had been subjected to striatal 6-OHDA infusion. STRING analysis confirmed a notable upregulation of eight hub genes (Notch3, Gng4, Itga3, Grin2d, Hgf, Fgf11, Htr3a, and Col6a2), along with a significant downregulation of two hub genes (Itga11 and Plp1), as validated by reverse transcription-quantitative polymerase chain reaction. This study provides a comprehensive transcriptomic profile of the hippocampi in a hemiparkinsonian rat model, thereby offering insights into the signaling pathways underlying hippocampal dysfunction.

Histological evaluation of the alpaca (Vicugna pacos) vomeronasal organ.

Little is known about the neuronal structure of the vomeronasal organ (VNO), a receptor organ responsible for pheromone perception, in the alpaca (Vicugna pacos). This study was performed to determine the localization of neuronal elements, including protein gene product 9.5 (PGP 9.5), a pan-neuronal marker, olfactory marker protein (OMP), a marker of mature olfactory receptor cells, and phospholipase C beta 2 (PLC-ß2), a marker of solitary chemoreceptor cells (SCCs), in the VNO. OMP was identified in receptor cells of the vomeronasal sensory epithelium (VSE), while PGP 9.5 and PLC-ß2 were localized in both the VSE and vomeronasal non-sensory epithelium. Collectively, these results suggested that the alpaca VNO possesses SCCs and olfactory receptor cells, which recognize both harmful substances and pheromones.

Key Genes in Olfactory Disorder in Experimental Autoimmune Encephalomyelitis Identified by Transcriptomic Analysis of the Olfactory Bulbs.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that shows demyelination in the central nervous system and functional deficits, including olfactory impairment. However, the genes related to olfactory impairment in EAE are unknown. We evaluated hub genes of the olfactory bulb in EAE mice. Differentially expressed genes (cut-offs, fold change > 2 and adjusted p < 0.05) and their related pathways in olfactory bulbs were subjected to gene ontology (GO) pathway analysis, gene set enrichment analysis (GSEA). Protein-protein interactions with selected genes were evaluated using the Search Tool for the Retrieval of Interacting Genes/Proteins. Gene regulatory networks (GRNs) which were constructed at the post-transcriptional level, including the genes-transcription factors (TFs) and gene-microRNAs (miRNAs) interaction networks. Twelve hub genes were found, three of which (Ctss, Itgb2, and Tlr2) were validated by RT-qPCR to be related to GO pathways such as immune response and regulation of immune response. GSEA showed that neuron-related genes-including Atp6v1g2, Egr1, and Gap43-and their pathways were significantly downregulated. GRNs analysis of six genes (Ctss, Itgb2, Tlr2, Atp6v1g2, Egr1, and Gap43) revealed 37 TFs and 84 miRNAs were identified as potential regulators of six genes, indicating significant interaction among six genes, TFs, and miRNAs. Collectively, these results suggest that transcriptomic analysis of the olfactory bulb of EAE mice can provide insight into olfactory dysfunction and reveal therapeutic targets for olfactory impairment.

Eugenol alleviates the symptoms of experimental autoimmune encephalomyelitis in mice by suppressing inflammatory responses.

Eugenol is a principal compound in essential clove oil, known for its anti-inflammatory and antioxidant properties. While recent studies have demonstrated its neuroprotective effects on central nervous system (CNS) injuries, such as brain ischemia/reperfusion injuries, but its potential impact on multiple sclerosis (MS), an autoimmune disease of the CNS, has not yet been explored. We evaluated the therapeutic effects of eugenol on experimental autoimmune encephalomyelitis (EAE), an established animal model of MS. EAE was induced in C57BL/6 mice using the myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. Clinical symptoms, including paralysis, were monitored daily, and levels of pro-inflammatory mediators were evaluated using real-time quantitative polymerase chain reaction, Western blot analyses, and immunohistochemistry. Daily oral administration of eugenol to MOG-induced EAE mice led to a notable decline in the severity of clinical symptoms. Eugenol inhibited EAE-related immune cell infiltration and the production of pro-inflammatory mediators. Histological examinations confirmed its ability to mitigate inflammation and demyelination in the spinal cord post-EAE induction. Eugenol alleviates neuroinflammation in the spinal cords of EAE-induced mice, primarily through anti-inflammatory action.

Eugenol ameliorates uveitis in mice with experimental autoimmune encephalomyelitis through the suppression of key inflammatory genes.

Visual impairment associated with uveitis is among the potential complications in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Bioinformatics analyses have shown that some hub genes are closely associated with the molecular mechanisms underlying uveitis in EAE. This study evaluated whether 4-allyl-2-methoxyphenol (eugenol) can mitigate the pathogenesis of uveitis in EAE through the interruption of key uveitogenic gene expression. Myelin oligodendrocyte glycoprotein35-55 (MOG) peptide-immunized C57BL/6 mice were injected intraperitoneally with eugenol. The eyeballs and spinal cords of EAE mice with or without eugenol treatment were collected simultaneously and immunohistochemical and molecular biological analyses were conducted. Eugenol treatment significantly ameliorated hindlimb paralysis. Ionized calcium-binding adapter molecule 1 (Iba-1) immunohistochemistry showed that the inflammatory response was significantly reduced in the uvea of eugenol-treated EAE mice compared with vehicle-treated controls. Eugenol also significantly reduced the expression of key uveitogenic genes including C1qb and Tyrobp. The suppressive effect of eugenol on inflammation was also observed in the spinal cord, as determined by the suppression of Iba-1-positive microglial cells. Together, these results suggest that the ameliorative effect of eugenol against EAE uveitis is associated with the suppression of key proinflammatory genes, which may represent targets for the treatment of uveitis.

Retinal transcriptome profiling identifies novel candidate genes associated with visual impairment in a mouse model of multiple sclerosis.

Visual impairment is occasionally observed in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Although uveitis and optic neuritis have been reported in MS and EAE, the precise mechanisms underlying the pathogenesis of these visual impairments remain poorly understood. This study aims to identify differentially expressed genes (DEGs) in the retinas of mice with EAE to identify genes that may be implicated in EAE-induced visual impairment. Fourteen adult mice were injected with myelin oligodendrocyte glycoprotein35-55 to induce the EAE model. Transcriptomes of retinas with EAE were analyzed by RNA-sequencing. Gene expression analysis revealed 347 DEGs in the retinas of mice with EAE: 345 were upregulated, and 2 were downregulated (adjusted p-value < 0.05 and absolute log2 fold change > 1). Gene ontology (GO) analysis showed that the upregulated genes in the retinas of mice with EAE were primarily related to immune responses, responses to external biotic stimuli, defense responses, and leukocyte-mediated immunity in the GO biological process. The expression of six upregulated hub genes (c1qb, ctss, itgam, itgb2, syk, and tyrobp) from the STRING analysis and the two significantly downregulated DEGs (hapln1 and ndst4) were validated by reverse transcription-quantitative polymerase chain reaction. In addition, gene set enrichment analysis showed that the negatively enriched gene sets in EAE-affected retinas were associated with the neuronal system and phototransduction cascade. This study provides novel molecular evidence for visual impairments in EAE and indicates directions for further research to elucidate the mechanisms of these visual impairments in MS.

Green Synthesis of Laser-Induced Graphene with Copper Oxide Nanoparticles for Deicing Based on Photo-Electrothermal Effect.

Homogenously dispersed Cu oxide nanoparticles on laser-induced graphene (LIG) were fabricated using a simple two-step laser irradiation. This work emphasized the synergetic photo-electrothermal effect in Cu oxide particles embedded in LIG. Our flexible hybrid composites exhibited high mechanical durability and excellent thermal properties. Moreover, the Cu oxide nanoparticles in the carbon matrix of LIG enhanced the light trapping and multiple electron internal scattering for the electrothermal effect. The best conditions for deicing devices were also studied by controlling the amount of Cu solution. The deicing performance of the sample was demonstrated, and the results indicate that the developed method could be a promising strategy for maintaining lightness, efficiency, excellent thermal performance, and eco-friendly 3D processing capabilities.

Direct Laser Interference Ink Printing Using Copper Metal-Organic Decomposition Ink for Nanofabrication.

In this study, we developed an effective and rapid process for nanoscale ink printing, direct laser interference ink printing (DLIIP), which involves the photothermal reaction of a copper-based metal-organic decomposition ink. A periodically lined copper pattern with a width of 500 nm was printed on a 240 µm-wide line at a fabrication speed of 17 mm/s under an ambient environment and without any pre- or post-processing steps. This pattern had a resistivity of 3.5 µΩ∙cm, and it was found to exhibit a low oxidation state that was twice as high as that of bulk copper. These results demonstrate the feasibility of DLIIP for nanoscale copper printing with fine electrical characteristics.

Highly Skin-Conformal Laser-Induced Graphene-Based Human Motion Monitoring Sensor.

Bio-compatible strain sensors based on elastomeric conductive polymer composites play pivotal roles in human monitoring devices. However, fabricating highly sensitive and skin-like (flexible and stretchable) strain sensors with broad working range is still an enormous challenge. Herein, we report on a novel fabrication technology for building elastomeric conductive skin-like composite by mixing polymer solutions. Our e-skin substrates were fabricated according to the weight of polydimethylsiloxane (PDMS) and photosensitive polyimide (PSPI) solutions, which could control substrate color. An e-skin and 3-D flexible strain sensor was developed with the formation of laser induced graphene (LIG) on the skin-like substrates. For a one-step process, Laser direct writing (LDW) was employed to construct superior durable LIG/PDMS/PSPI composites with a closed-pore porous structure. Graphene sheets of LIG coated on the closed-porous structure constitute a deformable conductive path. The LIG integrated with the closed-porous structure intensifies the deformation of the conductive network when tensile strain is applied, which enhances the sensitivity. Our sensor can efficiently monitor not only energetic human motions but also subtle oscillation and physiological signals for intelligent sound sensing. The skin-like strain sensor showed a perfect combination of ultrawide sensing range (120% strain), large sensitivity (gauge factor of ~380), short response time (90 ms) and recovery time (140 ms), as well as superior stability. Our sensor has great potential for innovative applications in wearable health-monitoring devices, robot tactile systems, and human-machine interface systems.