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Objective To explore the hub genes and the potential targets in the treatment of diabetes with TREM2 mutation-related cognitive dysfunction with bioinformatics analysis. Methods The cases of differential genes (DEGs) of diabetes mellitus and TREM2 mutation-related cognitive dysfunction were obtained respectively by microarray data analysis, the common differential genes were obtained by intersection between the two diseases. GO analysis, KEGG and Reactome pathway analysis were performed on the selected differential genes. The protein-protein interaction(PPI) network was constructed using online database. Finally, the effects of diabetes and TREM2 on spatial learning and memory of mice were detected by water maze, and the expression of hub gene SNAP25 was detected by Western blot. Results In both datasets, 19 genes showed similar changes, mainly enriched in biological processes and pathways related to neurons and metabolism. According to PPI analysis, DNER, GFAP, GRM5 and SNAP25 were identified as hub genes. Trem2 gene knockout aggravated spatial learning and memory impairment in diabetic mice. The expression of SNAP25 in hippocampus of diabetes mice was significantly increased, and then decreased after Trem2 knockout. Conclusions This study identified 19 TREM2-related genes in diabetes with cognitive dysfunction, among which 4 hub genes were found. These results provide a new experimental basis for the treatment of diabetes patients with cognitive impairment.

Objective To explore the expression of triggering receptor expressed on myeloid cells 2 (TREM2) in high-glucose microglia and to investigate the role of TREM2 in the proliferation, migration and phagocytosis of high-glucose microglia. Methods Microglia cells were divided into control group and high-glucose treatment group(67.5 mmol/L glucose, 24 h). The microglia cells were counted and the expression of Iba1 and TREM2 was detected. TREM2 siRNA was transfected to detect the proliferation and migration of microglia. The amyloid β-peptide (Aβ) with a fluorescent tag was added to observe the phagocytosis of Aβ by microglia. Results Compared to normal microglia, the number of microglia significantly decreased after high-glucose treatment (P＜0.001), while the expression of TREM2 and Iba1 markedly increased (P＜0.001). High glucose and TREM2 did not affect the proliferation of microglia. Compared to the normal group, the migration of microglia significantly decreased after high-glucose treatment (P＜0.05) and TREM2 did not affect the migration ability of high-glucose microglia. Compared to the normal group, the phagocytosis of Aβ by microglia significantly decreased in the high-glucose treated group(P＜0.001). Furthermore, TREM2 knockdown further decreased the phagocytosis of Aβ by high-glucose microglia (P＜0.001). Conclusions The expression of TREM2 in microglia significantly increases after high-glucose treatment, which significantly affects phagocytosis of Aβ by microglia.

Objective The role of activin A receptor type 1C(ACVR1C) in white matter remyelination and neurological outcome of mice with ischemic stroke were investigated. Methods Mice were randomly divided into empty virus vector sham operation group, adeno-associated virus(AAV) sham operation group, empty virus vector model group, AAV model group, empty virus vector activin group A and AAV activin group A.Acvr1cflox/flox mice with middle cerebral artery oclusion-reperfusion (MCAO/R) for 1 to 10 days were established. Adeno-associated virus AAV-PDGFRα-cre and AAV-PLP-cre with cre recombinase were injected into the lateral ventricles of the mice. Conditional knockout of Acvr1c on oligodendrocytes and oligodendrocytes. Neurological function score was used to observe the prognosis of neurological function. The expressions of ACVR1C protein and myelin basic protein (MBP) were detected by Western blot. Results With the extension of reperfusion time, activin A improved the behavioral outcome of mice by ACVR1C on oligodendrocytes at day 7 (P＜0.05), and significantly increased the expression of MBP protein in corpus callosum at day 10 (P＜0.05). Conclusions Activin A promotes white matter remyelination and improves outcomes of neurological function of ischemic stroke mice by acting on ACVR1C on oligodendrocytes.

Objective To investigate the regulation and mechanism of Herkinorin preconditioning on NOD-like receptor protein 3 (NLRP3) in brain tissue of transient middle cerebral artery occlusion (tMCAO) rats. Methods Rats were randomly divided into sham operation group (sham), model group (tMCAO) and Herkinorin group (Herkinorin). Before modeling, rats in Herkinorin group were intraperitoneally given Herkinorin (10 mg/kg) once a day for a week. The rats were evaluated by neurologic score, TTC staining, TUNEL staining 24 h after reperfusion. The expression levels of IκBα, p65, p-p65, pro-IL-1β, IL-1β, pro-caspase1, caspase1 p20 and NLRP3 were detected by Western blot. The binding level of IκBα to β-arrestin2 was detected by co-immunoprecipitation (Co-IP). Results Compared with sham group, rats in tMCAO group had higher behavioral score (P＜0.01), increased cerebral infarction percentage and increased cerebral edema rate (P＜0.01). The level of cell apoptosis was increased in ischemic penumbra (P＜0.01). The expression levels of IκBα and p65 were decreased (P＜0.01) and the expression levels of p-p65, IL-1β, caspase1 p20 and NLRP3 were increased in ischemic penumbra (P＜0.01). The binding level of IκBα to β-arrestin2 was decreased in ischemic penumbra (P＜0.01). Compared with tMCAO group, rats in Herkinorin group had lower behavioral score (P＜0.01), lower cerebral infarction percentage and lower cerebral edema rate (P＜0.01). The level of cell apoptosis was decreased in ischemic penumbra(P＜0.01). The expression of IκBα and p65 was increased (P＜0.01) and the expression of p-p65, IL-1β, caspase1 p20 and NLRP3 was decreased in ischemic penumbra (P＜0.01). The binding of IκBα to β-arrestin2 was increased in ischemic penumbra (P＜0.01). Conclusions Herkinorin may negatively regulate NF-κB/NLRP3 pathway to alleviate cerebral ischemia-reperfusion injury of tMCAO rats.

In order to ensure the straightening quality of spindle rod, reduce the labor intensity of workers and improve the working environment of workers, the causes of straightness error and deformation of spindle rod after hot rolling forming, longitudinal cutting forming, heat treatment and manual straightening were analyzed. The method of straightening the spindle rod with the automatic loading and unloading device of the manipulator on the thread rolling machine was adopted. With the method, the spindle rod was placed on the support plate between the two straightening rollers, and the moving roller moved forward, straightened, retreated and returned to the original position along the radial direction, with the spindle rod repeatedly bent and deformed along the axial direction through the spiral groove of the roller to achieve the purpose of straightening. At the same time, the structural characteristics and dimensions of the straightening roller and the support plate were introduced. The experimental results show that the spindle rod is straightened on the thread rolling machine after rough grinding, and the qualified rate is more than 90%; and the rod output reaches 3 000, which creates conditions for intelligent manufacturing of spindle rod.

BACKGROUND: Ischemic stroke (IS) is a life‑threatening condition with limited treatment options; thus, finding the potential key genes for novel therapeutic targets is urgently needed. This study aimed to explore novel candidate genes and pathways of brain microvessel endothelial cells (ECs) in IS by bioinformatics analysis. MATERIALS AND METHODS: The gene expression profiles of brain tissues or brain ECs in IS mice were downloaded from the online gene expression omnibus (GEO) to obtain the differentially expressed genes (DEGs) by R software. Functional enrichment analyses were used to cluster the functions and signaling pathways of the DEGs, while DEG‑associated protein–protein interaction network was performed to identify hub genes. The target microRNAs and competitive endogenous RNA networks of key hub genes were constructed by Cytoscape. RESULTS: Totally 84 DEGs were obtained from 6 brain tissue samples and 4 brain vascular EC samples both from IS mice in the datasets GSE74052 and GSE137482, with significant enrichment in immune responses, such as immune system processes and T‑cell activation. Eight hub genes filtered by Cytoscape were validated by two other GEO datasets, wherein key genes of interest were verified by reverse transcription‑polymerase chain reaction using an in vitro ischemic model of EC cultures. Our data indicated that AURKA and CENPF might be potential therapeutic target genes for IS, and Malat1/Snhg12/Xist‑miR‑297b‑3p‑CENPF, as well as Mir17 hg‑miR‑34b‑3p‑CENPF, might be RNA regulatory pathways to control IS progression. CONCLUSIONS: Our work identified two brain EC‑specific expressed genes in IS, namely, AURKA and CENPF, as potential gene targets for IS treatment. In addition, we presented miR‑297b‑3p/ miR‑34b‑3p‑CENPF as the potential RNA regulatory axes to prevent pathogenesis of IS. [ABSTRACT FROM AUTHOR]

Background: Perioperative cerebral ischemia/reperfusion injury is a major contributor to postoperative death and cognitive dysfunction in patients. It was reported that morphine preconditioning (MP) can mimic ischemia/hypoxia preconditioning to protect against ischemia/reperfusion injury. However, the mechanism of MP on the ischemia/reperfusion-induced neuronal apoptosis has not been fully clarified., Methods: The middle cerebral artery occlusion/reperfusion (MCAO/R) model of mice and the oxygen-glucose deprivation/reoxygenation (OGD/R) model in primary cortical neurons were used to mimic ischemic stroke. In vivo, the infarct size was measured by using TTC staining; NDSS, Longa score system, and beam balance test were performed to evaluate the neurological deficits of mice; the expression of the protein was detected by using a western blot. In vitro, the viability of neurons was determined by using CCK-8 assay; the expression of protein and mRNA were assessed by using western blot, RT-qPCR, and immunofluorescent staining; the level of apoptosis was detected by using TUNEL staining., Results: MP can improve the neurological functions of mice following MCAO/R (P<0.001, n=10 per group). MP can decrease the infarct size (P<0.001, n=10 per group) and the level of cleaved-caspase-3 of mice following MCAO/R (P<0.01 or 0.001, n=6 per group). MP can increase the levels of cPKCγ membrane translocation, p-p65, and cFLIPL, and decrease the levels of cleaved-caspase-8, 3 in neurons after OGD/R or MCAO/R 1 d (P<0.05, 0.01 or 0.001, n=6 per group). In addition, MP could alleviate OGD/R-induced cell apoptosis (P<0.001, n=6 per group)., Conclusion: MP alleviates ischemia/reperfusion-induced Caspase 8-dependent neuronal apoptosis through the cPKCγ-NF-κB-cFLIPL pathway., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)