1.Effects of BDNF pretreatment against cerebral ischemia-reperfusion injury in gerbils
Yongxing TAN ; Yihong JIANG ; Junxiong YU ; Xibao LOU ; Gaoxiang LIN
Chinese Journal of Emergency Medicine 2009;18(8):851-855
Objective To investigate the effects of brain-derived neurotrophic factor (BDNF) pretreatment on neuron apoptosis and the expression of Bcl-2 and Bax protein following global cerebral ischemia-reperfusion (I/R) injury in gerbils. Method Forty-eight mongolian gerbils were randomly divided into six groups in equal number (n = 8): normal control group (group C), ischemia-reperfusion group (group I/R) and four BDNF pretreatment groups according to various lengths of time from BDNF pretreatment to ischemia-reperfusion. The BDNF pretreat-ment was carried out in gerbils with lateral ventricular injection of BDNF 0.5μg 6 h, 12 h,24 h and 48 hours be-fore cerebral ischemia, and those gerbils assigned into PR6, PR12, PR24 and PR48 groups. The global cerebral is-chemia-reperfusion was induced by occlusion of bilateral common carotid arteries for 20 minutes and then the arter-ies were released for 24 hours reperfusion. The confirmation of global cerebra ischemia was evidenced by the ap-pearance of mydriasis and disappearance of light reflex and righting reflex. Twenty-four hours later, all gerbils including those of control group were sacrificed and a piece of tissue was taken from frontal cortex just behind the optic chiasma 1~4 millimeter for making paraffin sections. Neuron apoptosis was identified by using TUNEL and immunohischemistry was used to detect the expression of Bcl-2 and Bax protein in cerebral cortex. The data were analyzed by using analysis of variance. Results There were no apoptotic cells, and expression of Bcl-2 and Bax protein positive cells found in group C. Neuron apoptosis in brain cortex was detected in I/R group and BDNF pre-treatment groups. The indexes of neuron apoptosis in BDNF pretreatment groups were markedly lower than those in group I/R (P < 0.01). Compared with group I/R, the index of expression of Bcl-2 protein positive cells was in-creased significantly in BDNF pretreatment groups (P = 0.005), while the index of expression of Bax protein posi-tive cells were decreased significantly (P < 0.01 in all groups). Among 4 BDNF pretreatment group, the lowest apoptosis index and lowest of expression of Bax protein positive cells were found in PR6 and PR12 BDNF pretreat-ment groups (P = 0.0056 and 0.001, respectively). Conclusions Different time windows of BDNF pretreatment can decrease the neuron apoptosis in different degree, and protect brain against cerebral ischemia-reperfusion injury significantly. Among BDNF pretreatment time windows, pretreatment of 6 hours and 12 hours are the better ones.The mechanism of protection of BDNF pretreatment may be attributed to inducing Bcl-2 protein expressions and in-hibiting Bax protein expressions, and thereby inhibiting neuron apoptosis.
2.The risk factors of perioperative electrical storm in direct percutaneous coronary Intervention
Jianran XU ; Hailei HU ; Hongbo HUANG ; Jingfen YU ; Xibao SHI ; Yuewei CHEN ; Zhenbo CEN ; Yujian HU
Chinese Journal of Postgraduates of Medicine 2012;35(19):10-13
Objective To investigate the risk factors of electrical storm(ES) in patients with acute myocardial infarction (AMI) during perioperative period of direct percutaneous coronary intervention(PCI).Methods Forty-one AMI patients had been treated with direct PCI.The patients with perioperative ES were included in ES group and those without perioperative ES were included in conntrol group.ES was defined as the occurrence of spontaneous ventricular tachycardia or venicular fibrillation was twice or more within 24 h and unable to stop by itself and emergency treatment was needed.The difference of the clinical data between two groups were compared.Results There were 7 in 41 patients with direct PCI who had ES,the incidence was 17.07%,and 34 cases didn't have ES.Systolic pressure,diastolic pressure,white cell count,blood glucose,international normalized ratio and time duration from chest pain onset to direct PCI between two groups had no significant differences (P >0.05).Age,CK-MB,cardiac troponin I,the diameter of infarctrelated arleries(IRA ),incidence of reperfusion arrhythmia and mortality of ES group were all obviously higher than those of control group (P < 0.05 or < 0.01 ).The incidence of ES in patients whose IRA was left main artery or occlusion of middle section of two main coronary arteries,right coronary artery,left anterior descending branch and left circumflex artery was 66.67%(2/3),18.75%(3/16),11.76%(2/17) and O, respectively.Conclusions Perioperative ES during direct PCI most commonly occurrs in AMI patients with left main artery or occlusion of middle section of two main coronary artery.The diameter of IRA,TIMI flow classification after the patency of IRA and recanalization arrhythmia are the main risk factors of the occurrence of perioperative ES.
3.Small Non-coding Transfer RNA-Derived RNA Fragments (tRFs): Their Biogenesis, Function and Implication in Human Diseases.
Yu FU ; Inhan LEE ; Yong Sun LEE ; Xiaoyong BAO
Genomics & Informatics 2015;13(4):94-101
tRNA-derived RNA fragments (tRFs) are an emerging class of non-coding RNAs (ncRNAs). A growing number of reports have shown that tRFs are not random degradation products but are functional ncRNAs made of specific tRNA cleavage. They play regulatory roles in several biological contexts such as cancer, innate immunity, stress responses, and neurological disorders. In this review, we summarize the biogenesis and functions of tRFs.
Organelle Biogenesis*
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Humans*
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Immunity, Innate
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Nervous System Diseases
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Neurodegenerative Diseases
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RNA*
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RNA, Transfer
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RNA, Untranslated
4.Mechanism of long noncoding RNA LINC00987 promoting AML cell apop-tosis through cytochrome P450 pathway
Pengyue YANG ; Xuan LIU ; Yan WANG ; Ling XU ; Yangqiu LI ; Xibao YU
Chinese Journal of Pathophysiology 2024;40(2):265-273
AIM:To investigate the role and molecular mechanism of long noncoding RNA LINC00987 in the apoptosis of acute myeloid leukemia(AML)cells induced by antitumor drugs.METHODS:The LINC00987 expression in AML was detected by RT-qPCR.The Molm13 cells with stable knockdown of LINC00987 gene(shLINC00987)were constructed,and the effect of low LINC00987 expression on the apoptosis of AML cells induced by cytarabine was detected by annexin V/PI staining.Signaling pathway enrichment of LINC00987-coexpressed genes was performed to analyze the ef-fect of LINC00987 expression on cytochrome family genes.RESULTS:Compared with healthy individual group,the ex-pression of LINC00987 was significantly down-regulated in AML cell lines and patients,but highly up-regulated in the complete remission group after anti-AML treatment.In addition,low LINC00987 expression was associated with poor prog-nosis among the patients with AML.The LINC00987 expression in AML cell lines Molm13 and MV411 was significantly induced by antitumor drugs such as cytarabine,doxorubicin,arsenic trioxide,and venetoclax.Meanwhile,LINC00987 down-regulation could inhibit the apoptosis of Molm13 cells induced by cytarabine.The LINC00987-coexpressed genes were enriched in cytochrome P450(CYP450)-mediated oxidative stress pathways,and the LINC00987 expression was positively correlated with the expression of CYP450 family genes CYP11B1,CYP2U1 and CYP2C9.Down-regulation of LINC00987 could inhibit the mRNA expression of CYP11B1,CYP2U1 and CYP2C9 induced by cytarabine.CONCLU-SION:Long noncoding RNA LINC00987 can be used as a prognostic marker for AML and may promote cytarabine-in-duced AML cell apoptosis through CYP450-mediated oxidative stress pathways.