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Ischemic stroke is a common acute cerebrovascular disease in clinical practice, which poses a severe threat to human health. In recent years, with deepening understanding of ischemic stroke, significant progress has been made in the diagnosis and treatment. However, current treatments for ischemic stroke are partially limited due to extremely complex pathological mechanisms. Studies have shown that mitochondrial dysfunction plays an important role in the pathogenesis of ischemic stroke. Therefore, modulation of mitochondrial function through mitochondrial dynamics is essential to ameliorate the damage of cerebral ischemic neuronal cells. In this article, the molecular mechanism of mitochondrial dynamics and its role in ischemic stroke were reviewed, aiming to provide useful reference for the treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of acacetin on myocardial ischemia reperfusion injury in rats and its possible mechanism. 24 SPF rats were randomly divided into sham operation group, model control group, acacetin administration group, acacetin+AG490 group, with 6 rats in each group. Myocardial ischemia reperfusion injury model was induced by 30 minutes coronary occlusion followed by 2 h reperfusion in rats. The myocardial infarct area was measured by triphenyltetrazolium chloride, the activities of CK-MB and LDH in serum were detected by ultraviolet spectrophotometer and enzyme linked immunoassay, and the relative expression levels of Bcl-2, Bax, Stat3 and p-Stat3 proteins in myocardium were investigated by Western blot. Compared with the sham operation group, the activities of CK-MB and LDH in serum rose obviously in the model group (P<0.01), the percentage of myocardial infarction area increased significantly (P<0.01), the ratio of p-Stat3/Stat3 and Bcl-2/Bax decreased notably (P<0.01); Compared with the model group, the activities of CK-MB and LDH, the percentage of myocardial infarction area were significantly decreased (P<0.05), and the ratios of Bcl-2/Bax and p-Stat3/Stat3 were increased significantly in the acacetin treated group. However, the protective effect of acacetin on damaged myocardium was cleared by AG490 in the group of acacetin+AG490. Acacetin could alleviate myocardial damage and exert myocardial protection in MIRI rats, and its mechanism might be related to the inhibition of cardiomyocyte apoptosis by activating Jak2/Stat3 signal pathway. [ABSTRACT FROM AUTHOR]

Objective To investigate the protective mechanism of PCSK9 inhibitor against oxidative low-density lipoprotein (ox-LDL) induced injury of human umbilical vein endothelial cells (HUVECs). Methods HUVECs in logarithmic growth phase were divided into Control group (normal culture group), ox-LDL group (induced by 50 mg/L oxLDL for 24 h) and PCSK9 inhibitor groups (low, medium and high dose of PCSK9 inhibitor). The low, medium and high dose of PCSK9 inhibitor groups were treated with 5, 10 and 20 µmol/L PCSK9 inhibitors for 24 h and then induced by 50 mg/L ox-LDL for 24 h. Cell activity was detected by CCK-8 assay, and cell survival rates were calculated. Transcription and secretion levels of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) in supernatant of cell culture were determined by quantitative real time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Cell apoptosis was detected by flow cytometry. The expression levels of apoptosis-related proteins (Bax, Bcl-2, Cleaved-Caspase-3) and nuclear factor-κB (NF-κB) signaling pathway related proteins were detected by Western blot assay. Results Compared with the Control group, the cell survival rate was decreased, transcriptional and secretion levels of TNF-α, IL-6, MCP-1 were increased, apoptosis rate increased, pro-apoptotic proteins (Bax and cleaved Caspase-3) up-regulated, anti-apoptotic protein Bcl-2 down- regulated and phosphorylated NF-κB (p-NF-κB) expression increased in ox-LDL group. Meanwhile, the expression of NF-κB was up-regulated in the nucleus and down regulated in cytoplasm. Compared with ox-LDL group, the survival rates were increased in medium and high dose PCSK9 inhibitor groups after treatment with PCSK9 inhibitor. The transcription and secretion levels of TNF-α, IL-6, MCP-1 and apoptosis rate decreased. The results of Western blot assay showed that the expression levels of Bax and cleaved-Caspase-3 downregulated, Bcl-2 up-regulated and p-NF-κB decreased. PCSK9 inhibitors down-regulated the expression of NF-κB in the nucleus and up-regulated the expression of NF-κB in cytoplasm of HUVECs induced by ox-LDL (P < 0.05). Conclusion PCSK9 inhibitors can inhibit ox-LDL induced inflammatory response and cell apoptosis in HUVECs and play a protective role. [ABSTRACT FROM AUTHOR]

BACKGROUND: Whether controlling of post-injury inflammatory response combined with neural stem cell (NSC) transplantation can improve the curative efficacy for spinal cord injury still remains unclear. OBJECTIVE: To investigate the repair of spinal cord tissue, myelin regeneration, axon regeneration, motor function recovery and the possible mechanism after early application of tumor necrosis factor α antagonist (Etanercept) combined with tyrosine kinase C (TrkC) gene-modified NSC transplantation. METHODS: TrkC-overexpressed NSCs (TrkC-NSCs) were constructed by lentiviral transfection technique. The rat models of spinal cord transection injury were prepared, and then subjected to Etanercept combined with TrkC-NSCs transplantation. The number of neurons and neuroregeneration after injury were measured by Nissl's staining, immunofluorescence and western blot. The rat motor function was detected by Basso Beattie Bresnahan score and evoked potential. The myelin regeneration was detected by electron microscopy and toluidine blue staining. RESULTS AND CONCLUSION: Compared with the other groups, the Etanercept combined with TrkC-NSCs transplantation group had more survived anterior horn motor neurons at 28 days after injury, more myelin-encapsulated axons, higher Basso Beattie Bresnahan score, greater amplitude of the evoked potentials, and relatively shorter latency (all P < 0.05). These findings indicate that early application of tumor necrosis factor-α antagonist combined with TrkC-NSCs transplantation after spinal cord injury in rats can effectively promote myelin regeneration, axon regeneration, and further promote motor function recovery. [ABSTRACT FROM AUTHOR]