المؤلفون: Kezhou Liu, Zhengting Cai, Quanwei Zhang, Jiatong He, Yinuo Cheng, Shaonong Wei, Mengjie Yin

المصدر: CNS Neuroscience & Therapeutics. 28:1492-1508

مصطلحات موضوعية: Stroke, Pharmacology, Psychiatry and Mental health, Infarction, Physiology (medical), Autophagy, Humans, Pharmacology (medical), Ischemic Postconditioning, Ischemic Stroke

الوصف: To systematically review studies using remote ischemia postconditioning (RIPostC) for ischemic stroke in experimental models and obtain factors that significantly influence treatment outcomes.Peer-reviewed studies were identified and selected based on the eligibility criteria, followed by extraction of data on potentially influential factors related to model preparation, postconditioning, and measure time based on outcome measures including infarct size, neurological scales, and cell tests with autophagy, apoptosis, normal-neuron, and damaged-neuron counting. Then, all data were preprocessed, grouped, and meta-analyzed with the indicator of the standardized mean difference.Fifty-seven studies with 224 experiments (91 for infarct size, 92 for neurological scales, and 41 for cell-level tests) were included. There was little statistical difference between different model preparations, treated body parts, number of treatments, and sides. And treatment effect was generally a positive correlation with the duration of conditioning time to stroke onset with exceptions at some time points. Based on infarct size, the number of cycles per treatment, duration of occlusion, and release per cycle showed significant differences. Combined with the effect sizes by other measures, the occlusion/release duration of 8-10 min per cycle is better than 5 min, and three cycles per treatment were most frequently used with good effects. Effect also varied when measuring at different times, showing statistical differences in infarct size and most neurological scales. RIPostC is confirmed as an effective therapeutic intervention for ischemic stroke, while the RIPostC-mediated autophagy level being activated or inhibited remained conflicting.Conditioning time, number of cycles per treatment, duration of occlusion, and release per cycle were found to influence the treatment effects of RIPostC significantly. More studies on the relevant influential factors and autophagy mechanisms are warranted.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::414cb780eeb5df1d3542d2f5cd8b534fTest
https://doi.org/10.1111/cns.13925Test

المؤلفون: Chun-Yan, Li, Wei, Ma, Kuang-Pin, Liu, Jin-Wei, Yang, Xian-Bin, Wang, Zhen, Wu, Tong, Zhang, Jia-Wei, Wang, Wei, Liu, Jie, Liu, Yu, Liang, Xing-Kui, Zhang, Jun-Jun, Li, Jian-Hui, Guo, Li-Yan, Li

المصدر: Brain Research Bulletin. 185:39-48

مصطلحات موضوعية: MicroRNAs, Reperfusion Injury, General Neuroscience, Acyl-CoA Dehydrogenase, Long-Chain, Animals, Brain, RNA, Circular, RNA, Messenger, Ischemic Postconditioning, Brain Ischemia, Rats

الوصف: Remote ischemic postconditioning (RIPostC) is a protective procedure for brain damage caused by ischemia/reperfusion (IR), yet the mechanism of this treatment remains to be elucidated. Circular RNAs (circRNAs) are endogenous non-coding RNAs that have recently been recognized to play vital roles in ischemic brain injury. The aim of this study was to explore the role of circRNAs in the protective mechanism of RIPostC and to analyze the circRNA-microRNA (miRNA) regulation network in RIPostC. Nine rats were assigned randomly into three groups (three rats per group): sham, IR, and RIPostC. Their brain tissues were extracted for next-generation RNA sequencing and bioinformatics analysis was performed for two comparisons: sham vs. IR and IR vs. RIPostC. The expression patterns of selected circRNAs and miRNAs were validated by quantitative real-time PCR (qPCR). We detected 82 upregulated and 51 downregulated circRNAs and 137 upregulated and 127 downregulated miRNAs in the IR group compared with the sham group, and 41 upregulated and 100 downregulated circRNAs and 45 upregulated and 64 downregulated miRNAs in the RIPostC group compared with the IR group. The proposed competitive endogenous RNA (ceRNA) network, which included 24 circRNAs, 20 miRNAs, and 145 mRNAs, indicated that the dysregulated circRNAs played important roles in brain IR injury. On the basis of the expression patterns of selected circRNAs, miRNAs, and mRNAs obtained by qPCR, we proposed a circRNA_0002286-miR-124-3p-VLCAD pathway. In PC12 cell, the expression level of miR-124-3p was significantly upregulated when the expression of circRNA_0002286 was repressed and the expression level of VLCAD (very-long chain acyl-CoA dehydrogenase) was significantly downregulated, which suggested that circRNA_0002286 may act as a miRNA sponge for miR-124-3p to regulate the expression of VLCAD. We found that upregulation of circRNA_0002286 attenuated IR injury and was associated with downregulation of miR-124-3p and upregulation of VLCAD. This is the first time that circRNAs have been shown to be closely related to brain IR injury and RIPostC and suggests that targeting the circRNA_0002286-miR-124-3p-VLCAD pathway might attenuate brain IR injury.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cd6de326e6bbe10e714a96d2cdc03cbcTest
https://doi.org/10.1016/j.brainresbull.2022.04.006Test

المؤلفون: Guizhong Li, Ning Ding, Jiantuan Xiong, Shengchao Ma, Lin Xie, Lingbo Xu, Hui Zhang, Anning Yang, Yong Yang, Yideng Jiang, Huiping Zhang

المصدر: Oxidative Medicine and Cellular Longevity. 2022:1-29

مصطلحات موضوعية: MicroRNAs, Aging, Article Subject, Humans, Myocardial Reperfusion Injury, Myocytes, Cardiac, Cell Biology, General Medicine, Ischemic Postconditioning, Biochemistry, Adaptor Proteins, Signal Transducing, Epigenesis, Genetic

الوصف: Ischemic postconditioning (IPostC) has been proposed as a strategy to mitigate the risk of ischemia/reperfusion (I/R) injury, and autophagy is involved in I/R-induced aged myocardial injury, while the underlying mechanism of IPostC-regulated autophagy is unknown. Here, we implemented miRNA sequencing analysis in aged cardiomyocytes to identify a novel miR-181a-2-3p after HPostC, which inhibits autophagy by targeting AMBRA1 in aged myocardium to protect I/R-induced aged myocardial injury. Mechanistically, we identified that IPostC can induce DNA hypomethylation and H3K14 hyperacetylation of miR-181a-2-3p promoter due to the decreased binding of DNMT3b and HDAC2 at its promoter, which contributes to enhancing the expression of miR-181a-2-3p. More importantly, cooperation of DNMT3b and HDAC2 inhibits the binding of c-Myc at the miR-181a-2-3p promoter in aged cardiomyocytes. In summary, IPostC attenuates I/R-induced aged myocardial injury through upregulating miR-181a-2-3p expression, which is an attribute to transcriptional and epigenetic regulation of its promoter. Our data indicate that miR-181a-2-3p may be a potential therapeutic target against I/R injury in aged myocardium.

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الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee1d4be49f7312cc2294d1b36cb9c725Test
https://doi.org/10.1155/2022/9635674Test

المؤلفون: Hui-Sheng, Chen, Yu, Cui, Xiao-Qiu, Li, Xin-Hong, Wang, Yu-Tong, Ma, Yong, Zhao, Jing, Han, Chang-Qing, Deng, Mei, Hong, Ying, Bao, Li-Hong, Zhao, Ting-Guang, Yan, Ren-Lin, Zou, Hui, Wang, Zhuo, Li, Li-Shu, Wan, Li, Zhang, Lian-Qiang, Wang, Li-Yan, Guo, Ming-Nan, Li, Dong-Qing, Wang, Qiang, Zhang, Da-Wei, Chang, Hong-Li, Zhang, Jing, Sun, Chong, Meng, Zai-Hui, Zhang, Li-Ying, Shen, Li, Ma, Gui-Chun, Wang, Run-Hui, Li, Ling, Zhang, Cheng, Bi, Li-Yun, Wang, Duo-Lao, Wang, Juan, Feng

المصدر: JAMA

مصطلحات موضوعية: Male, China, General Medicine, Recovery of Function, Middle Aged, Article, Upper Extremity, Treatment Outcome, Humans, Female, Nervous System Diseases, Ischemic Postconditioning, Aged, Ischemic Stroke

الوصف: Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking.To assess the efficacy of RIC for acute moderate ischemic stroke.This multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021.Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971).The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set.Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group.Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention.ClinicalTrials.gov Identifier: NCT03740971.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2399207d9f2e5419af1b5da42eee94d9Test
https://pubmed.ncbi.nlm.nih.gov/35972503Test

المؤلفون: Jian, Wang, Wu, Wang, Chengying, Yan, Tianzhen, Wang

المصدر: Aging. 14:2748-2757

مصطلحات موضوعية: MicroRNAs, Aging, Reperfusion Injury, Animals, Endothelial Cells, Humans, Apoptosis, Rabbits, Cell Biology, Ischemic Postconditioning, Coronary Vessels

الوصف: Nonculprit lesions are closely related to the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). Our previous research found that ischemic postconditioning (IP) could inhibit the progression of nonculprit lesions. However, the mechanism by which IP regulates the occurrence and development of nonculprit lesions remains unclear.Firstly, a rabbit ischemia-reperfusion (IR) model was constructed. Next, the morphological characteristics of the coronary arterial tissues and myocardial tissues of the rabbits were observed using hematoxylin-eosin (HE) staining. Then, western blot was performed to detect the expressions of AT1, Cx43, β-tubulin, Bax, Bcl-2 and cleaved caspase 3. Finally, to further confirm the effect of IP on nonculprit coronary arterial tissues, anIR notably induced the cells apoptosis in nonculprit coronary arterial tissues and in myocardial tissues, while IR-induced cell apoptosis was significantly inhibited by IP. In addition, IP protected nonculprit coronary arterial tissues against IR via downregulating miR-92a, miR-328 and miR-494 and mRNA AT1, Cx43 and β-tubulin. Consistently, OGD/R-induced injury of Human umbilical vein endothelial cells (HUVECs) was reversed by IP.In this study, IP could protect nonculprit coronary arteries against IR injury via downregulating miR-92a, miR-328 and miR-494. Our findings may provide new directions for the treatment of nonculprit lesions.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5b76ba6152c02cb00db2c6c5046c6133Test
https://doi.org/10.18632/aging.203971Test

المؤلفون: Heng Jin, Xiaoxi Lin, Ziquan Liu, Jinqiang Wang, Jinxiang Wang, Yan Zhang, Chao Cao, Yanfen Chai, Songtao Shou

المصدر: European Journal of Trauma and Emergency Surgery. 48:4585-4593

مصطلحات موضوعية: Down-Regulation, Apoptosis, Acute Kidney Injury, Kidney, Critical Care and Intensive Care Medicine, Reperfusion Injury, parasitic diseases, Emergency Medicine, Animals, Orthopedics and Sports Medicine, Surgery, Rabbits, cardiovascular diseases, Ischemic Postconditioning, Biomarkers

الوصف: Background Acute renal failure due to crush syndrome is one of the leading causes of death in disasters. Ischemic Postconditioning (IPC) is a potentially effective strategy to protect against ischemic reperfusion injury, but a few studies noted its protective effect in crush induced acute kidney injury (AKI). Hence, this study investigated the optimal IPC strategy to prevent crush induced AKI and reveal related cellular mechanisms. Methods The right lower extremities of rabbits were constantly compressed for 8 h and then performed five cycles of clamping and releasing the femoral artery and vein before depression using a clip. In terms of the duration of clamping and releasing, the animals were randomly divided into 5 groups, Control, IPC-5sec, IPC-30sec, IPC-1min, and IPC-5min groups; 6 rabbits for each group. Biomarkers of inflammation, renal function, renal tubular injury, and muscular injury, apoptosis, and cellular senescence in kidney were detected. Results Six hours after decompression, the levels of Serum Creatine (SCr), Blood Urea Nitrogen (BUN), K+, and Interleukin-6 (IL-6) in IPC-1min and IPC-5min groups were lower than Control, with a statistically significant difference. The morphological study of Periodic Acid-Schiff (PAS) staining demonstrated that 6 h after decompression, IPC-1min can attenuate renal tubular damage renal tubule. Meanwhile, the level of Neutrophil Gelatinase-Associated Lipocalin (NGAL) in circulation in the IPC-30sec, IPC-1min, and IPC-5min groups was significantly decreased compared with the Control group, 2 h after decompression. On the other hand, the levels of serum Creatine Kinase (CK) and Myoglobin (Mb), and the morphological change of muscular damage detected by hematoxylin and eosin (H&E) staining in IPC-1min-treated group were significantly lower than Control group 6 hours after decompression. Further results of the cellular mechanism showed that the apoptotic markers of Terminal deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling (TUNEL) and Caspase3 and the cell senescent markers of senescence-associated β-galactosidase (SA-β-Gal) and nuclear LAMNB1 have changed significantly in the IPC-1min group, compared with the control group. Conclusions Performing 5 cycles of 1-min IPC would be a convenient, time-saving, and effective method to prevent crush-induced AKI by attenuating the release of nephrotoxic substances after decompression and downregulation of the expression of apoptosis and cellular senescence biomarkers.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::279f924d7ff3aba1c70cc11220cb197fTest
https://doi.org/10.1007/s00068-022-01910-5Test

المؤلفون: Hannah B. Andersen, Mads Andersen, Kristine Bennedsgaard, Sigrid Kerrn-Jespersen, Kasper J. Kyng, Ida E. Holm, Tine B. Henriksen

المصدر: Brogård Andersen, H, Andersen, M, Bennedsgaard, K T, Kerrn-Jespersen, S, Jacobsen Kyng, K, Holm, I E & Henriksen, T B 2022, ' No Differences in Cerebral Immunohistochemical Markers following Remote Ischemic Postconditioning in Newborn Piglets with Hypoxia-Ischemia ', Neuropediatrics, vol. 53, no. 6, pp. 423-431 . https://doi.org/10.1055/a-1889-8544Test

مصطلحات موضوعية: Vascular Endothelial Growth Factor A, piglet model, Swine, General Medicine, remote ischemic postconditioning, Disease Models, Animal, Hypoxia-Ischemia, Brain/pathology, Animals, Newborn, Ischemia, immunohistochemistry, Pediatrics, Perinatology and Child Health, Hypoxia-Ischemia, Brain, Animals, Humans, hypoxic-ischemic encephalopathy, Neurology (clinical), Hypoxia, Ischemic Postconditioning, Hypoxia-ischemia, Biomarkers, Ischemic Postconditioning/methods

الوصف: Background Despite therapeutic hypothermia, neonates with hypoxic–ischemic encephalopathy still develop neurological disabilities. We have previously investigated neuroprotection by remote ischemic postconditioning (RIPC) in newborn piglets following hypoxia–ischemia (HI). The aim of this study was to further investigate potential effects of RIPC on cerebral immunohistochemical markers related to edema, apoptosis, and angiogenesis. Methods Brain expression of aquaporin 4, caspase-3, B-cell lymphoma 2, and vascular endothelial growth factor was analyzed by immunohistochemistry in 23 piglets, randomly selected from a larger study of RIPC after HI. Twenty animals were subjected to 45 minutes of HI and randomized to treatment with and without RIPC, while three animals were randomized to sham procedures. RIPC was conducted by four conditioning cycles of 5-minute ischemia and reperfusion. Piglets were euthanized 72 hours after the HI insult. Results Piglets subjected to HI treated with and without RIPC were similar at baseline and following the HI insult. However, piglets randomized to HI alone had longer duration of low blood pressure during the insult. We found no differences in the brain expression of the immunohistochemical markers in any regions of interest or the whole brain between the two HI groups. Conclusion RIPC did not influence brain expression of markers related to edema, apoptosis, or angiogenesis in newborn piglets at 72 hours after HI. These results support previous findings of limited neuroprotective effect by this RIPC protocol. Our results may have been affected by the time of assessment, use of fentanyl as anesthetic, or limitations related to our immunohistochemical methods.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::110002a5431f6df97aed5326c8f8a158Test
https://pubmed.ncbi.nlm.nih.gov/35777661Test

المؤلفون: Zongyi, Xia, Bing, Chen, Chi, Zhou, Yitian, Wang, Jinyang, Ren, Xujin, Yao, Yifan, Yang, Qi, Wan, Zhexun, Lian

المصدر: BMC Cardiovascular Disorders. 22

مصطلحات موضوعية: Nicorandil, Phosphatidylinositol 3-Kinases, Heart Injuries, Myocardial Infarction, Animals, Creatine Kinase, MB Form, Myocardial Reperfusion Injury, Ischemic Postconditioning, Reactive Oxygen Species, Cardiology and Cardiovascular Medicine, Proto-Oncogene Proteins c-akt, Rats, Diabetes Mellitus, Experimental

الوصف: Background The diabetic heart exhibits a high sensitivity to ischaemia/reperfusion (I/R) injury. Diabetes mellitus (DM) can affect the efficacy of cardioprotective interventions and reduce the therapeutic potential of existing treatment options. This study aimed to investigate the feasibility of shifting from monotherapy to combination therapy in diabetic myocardial I/R injury. Methods 6–8 week rats were randomized into 10 groups: sham, I/R, ischaemia postconditioning (I-Post), nicorandil (Nic), combination therapy (I-Post + Nic), DM sham, DM I/R, DM I-Post, DM Nic and DM I-Post + Nic. The extent of myocardial injury was clarified by measuring CK-MB and NO levels in plasma, ROS content in myocardial tissues, and TTC/Evans Blue staining to assess the area of myocardial infarction. Pathological staining of cardiac tissue sections were performed to clarify the structural changes in myocardial histopathology. Finally, Western blotting was performed to detect the phosphorylation levels of some key proteins in the PI3K/Akt signalling pathway in myocardial tissues. Results We confirms that myocardial injury in diabetic I/R rats remained at a high level after treatment with I-Post or nicorandil alone. I-Post combined with nicorandil showed better therapeutic effects in diabetic I/R rats, and the combined treatment further reduced the area of myocardial injury in diabetic I/R rats compared with I-Post or nicorandil treatment alone (P P P Conclusion I-Post combined with nicorandil treatment maintains effective cardioprotection against diabetic myocardial I/R injury by activating the PI3K/Akt signalling pathway.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::832145c6e5acfad63fa54f9785ca9e63Test
https://doi.org/10.1186/s12872-022-02967-1Test

المؤلفون: Wei Ma, Kewei Zhu, Luwei Yin, Jinwei Yang, Jinfen Zhang, Hongjie Wu, Kuangpin Liu, Chunyan Li, Wei Liu, Jianhui Guo, Liyan Li

المصدر: Bioengineered. 13(6)

مصطلحات موضوعية: Adult, Reperfusion Injury, Brain Injuries, Humans, Bioengineering, RNA, Long Noncoding, General Medicine, Ischemic Postconditioning, Applied Microbiology and Biotechnology, Biotechnology, Ischemic Stroke

الوصف: Stroke is a main cause of disability and death among adults in China, and acute ischemic stroke accounts for 80% of cases. The key to ischemic stroke treatment is to recanalize the blocked blood vessels. However, more than 90% of patients cannot receive effective treatment within an appropriate time, and delayed recanalization of blood vessels causes reperfusion injury. Recent research has revealed that ischemic postconditioning has a neuroprotective effect on the brain, but the mechanism has not been fully clarified. Long non-coding RNAs (lncRNAs) have previously been associated with ischemic reperfusion injury in ischemic stroke. LncRNAs regulate important cellular and molecular events through a variety of mechanisms, but a comprehensive analysis of potential lncRNAs involved in the brain protection produced by ischemic postconditioning has not been conducted. In this review, we summarize the common mechanisms of cerebral injury in ischemic stroke and the effect of ischemic postconditioning, and we describe the potential mechanisms of some lncRNAs associated with ischemic stroke.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c4cafa42c6b75c0639f072da01e7d235Test
https://pubmed.ncbi.nlm.nih.gov/36420646Test

المؤلفون: Behnaz Mokhtari, Mahdi Abdoli-Shadbad, Alireza Alihemmati, Aniseh Javadi, Reza Badalzadeh

المصدر: Molecular Biology Reports. 49:1773-1782

مصطلحات موضوعية: Thioctic Acid, Ischemic Preconditioning, Myocardial, Autophagy, Genetics, Animals, Myocardial Reperfusion Injury, General Medicine, Ischemic Postconditioning, Molecular Biology, Diabetes Mellitus, Experimental, Mitochondria, Rats

الوصف: Investigating the interaction of diabetes with ischemic postconditioning (IPostC)-associated cardioprotection in myocardial ischemia/reperfusion (I/R) damage is of great clinical importance. The present work was designed to determine the possible synergistic effects of alpha-lipoic acid (LA) preconditioning and IPostC on myocardial I/R damage in type-II diabetic rats through modulating autophagy, and the involvement of mitochondrial function.High-fat diet/low dose of streptozotocin-induced type-II diabetic model with duration of 12 weeks was used in this study. LA (100 mg/kg/day) was administered orally in diabetic rats for 5 weeks before I/R. Myocardial I/R was established on Langendorff apparatus through the ligation of left anterior descending coronary artery for 35 min, then reperfusion for 60 min. IPostC was carried out immediately at the beginning of the reperfusion. At the end of the experiment, myocardial infarct size (IS), autophagy markers at both gene and protein levels, and mitochondrial ROS production and membrane potential were assessed.Combined conditioning with LA and ischemia significantly decreased the IS of diabetic hearts (P0.05), however, single therapies had no significant effects. LA in combination with IPostC more significantly decreased LC3 and p62 mRNA levels (P0.01), and LC3II/LC3I and p62 protein levels (P0.01). Also, this combined therapy decreased mitochondrial ROS generation and membrane depolarization (P0.01).Pretreatment with LA in diabetic rats notably restored cardioprotection by IPostC via modulating autophagy and restoring mitochondrial function. This combined conditioning might be an effective strategy to diminish I/R damage in diabetic hearts.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::76f696e918a308a96714961536e005f1Test
https://doi.org/10.1007/s11033-021-06987-6Test