Secondary lung injury after SCI is a major cause of patient mortality, with apoptosis playing a key role. This study aimed to explore the impact of treadmill training and miR145-5p on the MAPK/Erk signaling pathway and apoptosis in rats with complete SCI. SD rats were used to establish T10 segmental complete SCI models and underwent treadmill training 3, 7, or 14 days postinjury. Various techniques including arterial blood gas analysis, lung wet/dry weight ratio, HE staining, immunofluorescence staining, immunohistochemical staining, qRT-PCR, and Western blotting were employed to assess alterations in lung function and the expression levels of crucial apoptosis-related factors. In order to elucidate the specific mechanism, the impact of miR145-5p on the MAPK/Erk pathway and its role in apoptosis in lung cells were confirmed through miR145-5p overexpression and knockdown experiments. Following spinal cord injury (SCI), an increase in apoptosis, activation of the MAPK/Erk pathway, and impairment of lung function were observed in SCI rats. Conversely, treadmill training resulted in a reduction in alveolar cell apoptosis, suppression of the MAPK/Erk pathway, and enhancement of lung function. The gene MAP3K3 was identified as a target of miR145-5p. The influence of miR145-5p on the MAPK/Erk pathway and its impact on apoptosis in alveolar cells were confirmed through the manipulation of miR145-5p expression levels. The upregulation of miR145-5p in spinal cord injury (SCI) rats led to a reduction in MAP3K3 protein expression within lung tissues, thereby inhibiting the MAPK/Erk signaling pathway and decreasing apoptosis. Contrarily, rats with miR145-5p knockdown undergoing treadmill training exhibited an increase in miR145-5p expression levels, resulting in the inhibition of MAP3K3 protein expression in lung tissues, suppression of the MAPK/Erk pathway, and mitigation of lung cell apoptosis. Ultimately, the findings suggest that treadmill training may attenuate apoptosis in lung cells post-spinal cord injury by modulating the MAP3K3 protein through miR145-5p to regulate the MAPK/Erk signaling pathway.

Objective:To investigate the effect and mechanism of treadmill training on Purkinje cells in the cerebellum of the rats with spinal cord injury(SCI). Method:Total of 108 female SD rats were randomly divided into 3 groups:the sham-operated group,the SCI group,and the SCI+treadmill training(TT)group.The rats in the SCI exercise group started treadmill train-ing after surgery,and BBB scores were used to assess the hindlimb motor function of rats with spinal cord in-jury.The cerebellum tissues were collected on the 3,7 and 14 day after surgery respectively,and the number and morphological changes of Purkinje cells in the cerebellum were detected by HE staining and Nissler stain-ing.The expression of caspase-9 and mGluR1 in Purkinje cells was detected by immunohistochemistry;the ex-pression of caspase-3 and mGluR1 was detected by immunofluorescence;the expression of apoptosis-related proteins Bax,Bcl-2,Cyt-C,caspase-9 and caspase-3 in cerebellar tissue was detected by Western Blot. Result:Compared with the sham-operated group,the BBB scores in SCI and SCI+TT groups were significant-ly decreased(P＜0.05).The number of Purkinje cells in cerebellum was reduced,and the size was reduced and lost the normal morphology.The expression levels of apoptosis-related proteins Bax,Cyt-C,activated caspase-9,and activated caspase-3 proteins in cerebellum were significantly increased(P＜0.05),and Bcl-2 expression was significantly decreased;caspase-9 and caspase-3 expression was increased and mGluR1 expression was decreased in Purkinje cells(P＜0.05).Compared with the SCI group,there was no significant difference in the BBB scores of the SCI+TT group(P＞0.05);the number and normal morphology of Purkinje cells in cerebellum increased;the expression levels of apoptosis-related proteins Bax,Cyt-C,activated caspase-9 and activated caspase-3 de-creased(P＜0.05),and the expression of Bcl-2 increased;the expression levels of caspase-9 and caspase-3 in Pur-kinje cells were decreased,and the expression level of mGluR1 was significantly increased(P＜0.05). Conclusion:Treadmill training can reduce the apoptosis of Purkinje cells in the cerebellum of the rats with spi-nal cord injury through the mitochondrial apoptosis pathway.

investigate intermittent theta-burst stimulation (iTBS) effect on ischemic stroke and the underlying mechanism of neurorehabilitation, we developed an ischemia/reperfusion (I/R) injury model in Sprague-Dawley (SD) rats using the middle cerebral artery occlusion/reperfusion (MCAO/r) method. Next, using different behavioral studies, we compared the improvement of the whole organism with and without iTBS administration for 28 days. We further explored the morphological and molecular biological alterations associated with neuronal apoptosis and neuroinflammation by TTC staining, HE staining, Nissl staining, immunofluorescence staining, ELISA, small RNA sequencing, RT-PCR, and western blot assays. The results showed that iTBS significantly protected against neurological deficits and neurological damage induced by cerebral I/R injury. iTBS also significantly decreased brain infarct volume and increased the number of surviving neurons after 28 days. Additionally, it was observed that iTBS decreased synaptic loss, suppressed activation of astrocytes and M1polarized microglia, and simultaneously promoted M2-polarized microglial activation. Furthermore, iTBS intervention inhibited neuronal apoptosis and exerted a positive impact on the neuronal microenvironment by reducing neuroinflammation in cerebral I/R injured rats. To further investigate the iTBS mechanism, this study was conducted using small RNA transcriptome sequencing of various groups of peri-infarcted tissues. Bioinformatics analysis and RT-PCR discovered the possible involvement of miR-34c-5p in the mechanism of action. The target genes prediction and detection of dual-luciferase reporter genes confirmed that miR-34c-5p could inhibit neuronal apoptosis in cerebral I/R injured rats by regulating the p53/Bax signaling pathway. We also confirmed by RT-PCR and western blotting that miR-34c-5p inhibited Bax expression. In conclusion, our study supports that iTBS is vital in inhibiting neuronal apoptosis in cerebral I/R injured rats by mediating the miR-34c-5p involvement in regulating the p53/Bax signaling pathway.& COPY; 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

Spinal cord injury (SCI) leads to severe intestinal dysfunction and decreased motility. There is an interaction between the intestine and the nervous system, intestinal intervention through microbial regulation and exercise is a potential treatment option for spinal cord injury. We investigated the effects of swimming rehabilitation training combined with fecal microbial transplantation on intestinal as well as neurological functions in rats with spinal cord injuries, and explored the potential mechanisms. The animals were randomly divided into five groups: sham-operated control group (Sham), spinal cord injury only group (SCI), swimming training group (Swimming), fecal microbial transplantation group (FMT) and combined interventions group (Combined). Behavioral assessments, pathological and immunological analyses were performed after the interventions. Compared to rats in the spinal cord injury group, rats subjected to swimming training, fecal microbial transplantation and combined interventions group exhibited improved intestinal transit, barrier functions, motility, and motor conduction pathway conductivity(P < 0.05). The combined interventions group had better outcomes(P < 0.01). In addition, combined interventions significantly suppressed inflammatory factor levels (P < 0.05) in the colon and spinal cords and significantly protected forefoot motor neurons (NeuN) in the spinal cord injury area, inhibiting astrocyte activation and reducing the expressions of the signature glial fibrillary acidic protein (GFAP) and markers of microglia (Iba-1) at the lesion site(P < 0.05). In conclusion, all effects of combined swimming training and fecal microbial transplantation interventions were superior to swimming training or fecal microbial transplantation alone. Swimming training and fecal microbial transplantation interventions have a synergistic effect on the recovery of intestinal function and motility after spinal cord injury. The mechanism of mutual facilitation between gut function and motility may be related to the brain-gut axis interaction.

目的:探讨跑台运动训练对脊髓损伤(SCI)后大鼠肺损伤及HMGB1/TLR4/NF-κB信号通路表达的影响.方法:选取54只SD雌性大鼠,随机分成3组,包括假手术组、SCI制动组、SCI运动组.SCI运动组及SCI制动组分别于术后第3天开始跑台运动训练或制动干预,BBB评分评定大鼠脊髓损伤后后肢运动功能.分别在运动或制动后第3天、第7天取肺组织,HE染色检测大鼠肺组织病理结构变化;免疫组化检测肺组织HMGB1蛋白表达情况;qRT-PCR检测HMGB1、TLR4、NF-κB、IL-1β、IL-6、TNF-α mRNA表达情况;Western Blot检测 HMGB1、TLR4、NF-κB蛋白表达情况.结果:BBB评分结果显示,与假手术组比较,SCI制动组、SCI运动组BBB评分均显著下降(P＜0.05);SCI运动组与SCI制动组评分结果比较无显著性差异(P＞0.05).HE染色结果显示,SCI制动组及SCI运动组第3天、第7天肺组织中均出现水肿、出血、炎性细胞浸润,相较于SCI制动组,SCI运动组肺损伤评分显著降低(P＜0.05).qRT-PCR、免疫组化、Western Blot结果均显示,与假手术比较,SCI制动组、SCI运动组第3天、第7天肺组织中HMGB1、TLR4、NF-κB、IL-1β、IL-6、TNF-α等因子的表达均显著上调(P＜0.05),且SCI运动组较SCI制动组显著降低(P＜0.05).结论:跑台运动训练可改善脊髓损伤后大鼠肺损伤,其机制可能与调节HMGB1/TLR4/NF-κB信号通路,抑制肺组织炎症反应相关.

Objective: To investigate the effects of treadmill training on lung injury and HMGB1/TLR4/NF-kappa B after spinal cord injury (SCI) in rats. Methods: A total of 108 female SD rats were randomly divided into three groups: sham operation group, SCI brake group, and SCI exercise group. The rats in the SCI exercise group began treadmill training on the 3rd day after the operation. The rats in the SCI brake group underwent braking treatment. The lung tissues were obtained on the 3rd, 7th, and 14th days after exercise. Locomotor functional recovery was determined using the BBB scores and inclined plane test. Respiratory function was determined via abdominal aortic blood gas analysis. HE staining was used to detect pathological changes in rat lung tissue. RNA sequencing was used to identify differentially expressed genes at different phases in each group of lung tissues. HMGB1, TLR4, and NF-kappa B in lung tissue were detected using immunohistochemistry and immunofluorescence. Detection of HMGB1 levels in serum, spinal cord tissues and lung tissues by ELISA. HMGB1, TLR4, NF-kappa B, IL-1 beta, IL-6, TNF-alpha mRNA, and protein expression levels were detected via qRT PCR and western blot. Results: Motor and respiratory functions significantly decreased after SCI (P < 0.05). However, locomotion and respiratory functions were significantly improved after treadmill training intervention (P < 0.05). HE staining showed that interstitial thickening, inflammatory cells, and erythrocyte infiltration occurred in lung tissue of rats after SCI (P < 0.05). Moreover, inflammatory reaction in lung tissue was significantly reduced after treadmill training intervention (P < 0.05). A total of 428 differentially expressed mRNAs [(|log2(FC)| > 2, P < 0.05)] were identified in the intersection of the three groups. KEGG analysis identified five enriched signal pathways, including NF-kappa B. ELISA results showed that treadmill training could significantly reduce the levels of HMGB1 in serum, spinal cord tissue and lung tissue that were elevated after SCI (P < 0.05). Immunohistochemistry, immunofluorescence, qRT PCR, and Western blot showed that HMGB1, TLR4, IL-1 beta, IL-6, TNF-alpha, and NF-kappa B expressions were significantly up-regulated at the 3rd, 7th and 14th days after SCI, compared with the sham group. Besides, inflammatory cytokines were significantly lower in the SCI exercise group than in the SCI brake group at all time points after intervention (P < 0.05). Conclusion: Treadmill training alleviates lung tissue inflammation and promotes recovery of motor and respiratory functions by inhibiting the HMGB1/TLR4/NF-kappa B signaling pathway after SCI in rats.

目的 对UC活动期及恢复期的差异基因进行生物信息学分析,探讨影响UC发生和发展的可能机制.方法 从GEO数据库下载正常人及UC患者活动期及恢复期结直肠黏膜基因芯片数据,进行差异基因筛选、基因本体论和DEGs富集分析、构建PPI网络及解析核心关键基因.结果 交叉分析显示,在UC活动期表达上调而恢复期表达下调的基因有202个;GO分析发现,差异基因在炎症反应、趋化因子介导的信号通路以及白细胞迁移等生物过程中显著富集;KEGG分析显示,差异基因显著富集在补体和凝血级联反应途径、趋化因子信号通路途径、细胞因子—细胞因子受体相互作用途径、Toll样受体信号通路等;通过Cytoscape构建PPI网络,利用cytohubba中的三种算法筛选解析到CCL2等10个核心关键基因.结论 本研究初步揭示了影响UC进展的关键基因和信号通路,加深了我们对UC发生和发展的分子机制的认识,其中解析到的核心关键基因有望成为溃疡性结肠炎诊断和治疗的分子靶标.