摘要：
The target lengths of gene-editing enzymes vary from approximately 20 to 80 nucleotides. The ideal reporter genes should be able to tolerate the insertion of target sequences to differentiate the phenotypic changes between in-frame and frame shift mutations for evaluating the enzymatic activities and off-target effects of gene-editing enzymes such as zinc finger nucleases, transcription activator-like effector nucleases, clustered regularly interspaced short palindromic repeats-associated system. This study demonstrated that the zeocin resistance gene (ZeoR) tolerated the insertion of long targets for a variety of tests using a strategy of inserting tandem repeats of NNT. Four genes such as CCR5, AR, HPV 16E7 early gene, and EGFR applications of ZeoR in quantitatively analyzing the off-targets of CRISPR were successful. The data indicated that evaluating the enzymatic activities and off-target effects with assays employing ZeoR had great potential in facilitating the application of gene editing to human gene therapy.
期刊：
Cancer Cell International,2019年19(1):1-13 ISSN：1475-2867
通讯作者：
Luo, Dixian
作者机构：
[Li, Jia; Hu, Zheng; Luo, Wenna; He, Rongzhang; Luo, Weihao; Duan, Lili; Luo, Dixian; Wang, Qingmei; Tan, Tan] Univ South China, Peoples Hosp Chenzhou 1, Natl & Local Joint Engn Lab High High Throughput, Translat Med Inst, Chenzhou 423000, Peoples R China.;[Luo, Dixian; Wang, Qingmei; Tan, Tan] Univ South China, Peoples Hosp Chenzhou 1, Ctr Clin Pathol, Chenzhou 423000, Peoples R China.;[He, Rongzhang] Cent S Univ, Xiangya Hosp, Dept Clin Pharmacol, Changsha 410078, Hunan, Peoples R China.
通讯机构：
[Luo, Dixian] U;Univ South China, Peoples Hosp Chenzhou 1, Natl & Local Joint Engn Lab High High Throughput, Translat Med Inst, Chenzhou 423000, Peoples R China.
摘要：
Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke (AIS) who are treated with tissue plasminogen activator (tPA). HT is associated with high morbidity and mortality, but no effective treatments are currently available to reduce the risk of HT. Therefore, methods to prevent HT are urgently needed. In this study, we used IM-12, an inhibitor of glycogen synthase kinase 3beta (GSK-3beta), to evaluate the role of the Wnt-beta-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke, and then were either administered rtPA, rtPA combined with IM-12, or the vehicle at 4 h after stroke was induced. Our results indicate that rats subjected to HT had more severe neurological deficits, brain edema, and blood-brain barrier (BBB) breakdown, and had a greater infarction volume than the control group. Rats treated with IM-12 had improved outcomes compared with those of rats treated with rtPA alone. Moreover, IM-12 increased the protein expression of beta-catenin and downstream proteins while suppressing the expression of GSK-3beta. These results suggest that IM-12 reduces rtPA-induced HT and attenuates BBB disruption, possibly through activation of the Wnt-beta-catenin signaling pathway, and provides a potential therapeutic strategy for preventing tPA-induced HT after AIS.
关键词：
apoptosis;atherosclerosis;inflammation;macrophage;nuclear factor-kappaB;protein kinase B;tumor necrosis factor-alpha-induced protein 8-like 2
摘要：
Macrophage apoptosis and inflammation serve pivotal roles in the occurrence of atherosclerosis. However, the detailed underlying mechanism of macrophage action during atherosclerosis is poorly understood. Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) is a well-known negative regulator of the immune response. The current study assessed the association between TIPE2 and apoptosis-associated molecules in macrophages during atherosclerosis, as well as the role of TIPE2 in macrophage inflammation. RAW264.7 macrophages were subsequently transfected with a TIPE2 expression plasmid. Following oxidized low-density lipoprotein (oxLDL) induction (100 microg/m1) for 48 h, macrophage apoptosis was assessed via Annexin V/propidium iodide dual staining. The apoptosis-associated factors and Akt signaling pathway-associated factors were also evaluated via western blot analysis. The expression of inflammatory factors was determined via a reverse transcription-quantitative polymerase chain reaction assay and western blotting. Furthermore, a transwell assay was performed to test cell invasion ability. NF-kappaB phosphorylation and nuclear translocation were also assessed via western blotting. The results demonstrated that TIPE2 overexpression may promote oxLDL-induced RAW264.7 macrophage apoptosis by inhibiting the protein kinase B (Akt) signaling pathway. Furthermore, it was demonstrated that TIPE2 significantly reduced oxLDL-induced tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and monocyte chemoattractant protein 1 expression (MCP-1), and increased IL-10 expression by suppressing NF-kappaB phosphorylation and nuclear translocation in RAW264.7 macrophages. These results indicated that TIPE2 serves a protective role in oxLDL-induced RAW264.7 macrophages, and its mechanism may partly be exerted via the inhibition of the PI3K/Akt signaling pathway and the reduction of the macrophage inflammatory response achieved via the suppression of NF-kappaB signal activation.
摘要：
Atrial fibrillation (AF) is associated with metabolic stress and induces myocardial fibrosis reconstruction by increasing glycolysis. One goal in the treatment of paroxysmal AF (p-AF) is to improve myocardial fibrosis reconstruction and myocardial metabolic stress caused by the Warburg effect. Adopted male canine that rapid right atrial pacing (RAP) for 6 days to establish a p-AF model. The canines were pre-treated with phenylephrine (PE) or dichloroacetic acid (DCA) before exposure to p-AF or non-p-AF. P-wave duration (P-max), minimum P-wave duration (P-min), P wave dispersion (PWD), atrial effective refractory period (AERP) and AERP dispersion (AERPd) were measured in canine atrial cardiomyocytes. Pyruvate dehydrogenase kinase-1 (PDK-1), PDK-4, lactate dehydrogenase A (LDHA), pyruvate dehydrogenase (PDH), citrate synthase (CS), isocitrate dehydrogenase (IDH), and matrix metalloproteinase 9 (MMP-9) were evaluated by western blotting and reverse transcription polymerase chain reaction (RTPCR), content of adenosine monophosphate (AMP), adenosine triphosphate (ATP), lactic acid and glycogen, and activity of LDHA, PDK-1 and PDK-4 were evaluated by enzyme-linked immunosorbent assay (ELISA), myocardial tissue glycogen content was evaluated by PAS, myocardial fibrosis remodeling was evaluated by hematoxylin and eosin (H&E) and Masson staining. Our findings demonstrated that p-AF increases the Warburg effect-related metabolic stress and myocardial fibrosis remodeling by increasing the expression and activity of PDK-1, PDK-4, and LDHA, content of AMP and lactic acid, and the ratio of AMP/ATP and decreasing the expression of PDH, CS, and IDH, and glycogen content. In addition, p-AF can induce cardiomyocyte fibrosis remodeling and increase MMP-9 expression, and p-AF also increases atrial intracardiac waveform activity by prolonging P-max, P-min, PWD, and AERPd and shortening AERP. PDK isoforms agonists (PE) produce a similar p-AF pathological effect and can produce synergistic effects with p-AF, further increasing Warburg effect-related metabolic stress, myocardial fibrosis remodeling, and atrial intracardiac waveform activity. In contrast, the use of PDK-specific inhibitors (DCA) completely reverses these pathophysiological changes induced by p-AF. We demonstrate that p-AF can induce the Warburg effect in canine atrial cardiomyocytes and significantly improve p-AF-induced metabolic stress, myocardial fibrosis remodeling, and atrial intracardiac waveform activity by inhibiting the Warburg effect. (C) 2019 Elsevier Inc. All rights reserved.
摘要：
Overlap extension polymerase chain reaction (PCR) is a powerful technology for DNA assembly. Based on this technology, we synthesized DNA templates, which were transcribed into sgRNA in vitro, and further detected their efficiency of purified sgRNAs with Cas9 nuclease. The sgRNAs synthesized by this approach can effectively cleave the DNA fragments of interest in vitro and in vivo. Compared with the conventional method for generating sgRNA, it does not require construction of recombinant plasmids and design of primers to amplify sgRNA core fragment. Only several short primers with overlapped sequences are needed to assemble a DNA fragment as the template of sgRNA. This modified and simplified method is highly applicable and less time-consuming.
期刊：
Journal of Cellular and Molecular Medicine,2019年23(10):6919-6929 ISSN：1582-1838
通讯作者：
Wang, Jingfeng;Liang, Ying
作者机构：
[Yuan, Woliang; Lin, Yongqing; Zhang, Haifeng; Yang, Ying; Wang, Jingfeng; Xie, Yong] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Cardiol, Guangzhou 510120, Guangdong, Peoples R China.;[Tian, Guoping] Univ South China, Affiliated Hosp 2, Dept Cardiovasc Med, Hengyang, Peoples R China.;[Liang, Ying] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Endocrinol, Guangzhou 510120, Guangdong, Peoples R China.
通讯机构：
[Wang, Jingfeng; Liang, Ying] S;Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Cardiol, Guangzhou 510120, Guangdong, Peoples R China.;Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Endocrinol, Guangzhou 510120, Guangdong, Peoples R China.
摘要：
The present study investigated the role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 16 (SNHG16) in the human aortic smooth muscle cell (HASMC) proliferation and migration and explored the potential link between SNHG16 and atherosclerosis. Our results showed that platelet-derived growth factor (PDGF)-bb treatment promoted cell proliferation and migration with concurrent up-regulation of SNHG16 in HASMCs. Small nucleolar RNA host gene 16 overexpression promoted HASMC proliferation and migration, while SNHG16 knockdown suppressed cell proliferation and migration in PDGF-bb-stimulated HASMCs. The bioinformatic analyses showed that SNHG16 possessed the complementary binding sequence with miR-205, where the interaction was confirmed by luciferase reporter assay and RNA pull-down assay in HASMCs, and SNHG16 inversely regulated miR-205 expression. MiR-205 overexpression attenuated the enhanced effects of PDGF-bb treatment on HASMC proliferation and migration. Moreover, Smad2 was targeted and inversely regulated by miR-205, while being positively regulated by SNHG16 in HASMCs. Smad2 knockdown attenuated PDGF-bb-mediated actions on HASMC proliferation and migration. Both miR-205 overexpression and Smad2 knockdown partially reversed the effects of SNHG16 overexpression on HASMC proliferation and migration. Moreover, SNHG16 and Smad2 mRNA were up-regulated, while miR-205 was down-regulated in the plasma from patients with atherosclerosis. Small nucleolar RNA host gene 16 expression was inversely correlated with miR-205 expression and positively correlated with Smad2 expression in the plasma from atherosclerotic patients. In conclusion, our data showed the up-regulation of SNHG16 in pathogenic-stimulated HASMCs and clinical samples from atherosclerotic patients. Small nucleolar RNA host gene 16 regulated HASMC proliferation and migration possibly via regulating Smad2 expression by acting as a competing endogenous RNA for miR-205.
作者机构：
[Wang, Siyang; Liu, Zhigang; Liu, Qiaodan; Yao, Jijin] Sun Yat Sen Univ, Phase 1 Clin Trial Ward, Dept Head & Neck Oncol, Canc Ctr,Affiliated Hosp 5, Zhuhai 519001, Peoples R China.;[Zhou, Jiao; Liu, Guiyun; Xu, Chenyang; Liu, Fengzin; Jiang, Rong] Cent S Univ, Xiangya Sch Med, Affiliated Canc Hosp, Dept Radiat Oncol,Hunan Canc Hosp, Changsha 410000, Hunan, Peoples R China.;[Zhou, Jiao; Liu, Guiyun; Xu, Chenyang; Liu, Fengzin; Jiang, Rong] Univ South China, Dept Clin Med, Hengyang 421000, Peoples R China.;[Jiang, Wen] Univ Texas Southwestern Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA.
通讯机构：
[Liu, Zhigang] S;Sun Yat Sen Univ, Phase 1 Clin Trial Ward, Dept Head & Neck Oncol, Canc Ctr,Affiliated Hosp 5, Zhuhai 519001, Peoples R China.
摘要：
Nasopharyngeal carcinoma (NPC) is endemic in southern China. Due to the unique anatomical and biological properties of NPCs, radiotherapy or combined modality based on radiotherapy is an effective treatment option. Helical tomotherapy (HT) is an emerging intensity modulated radiotherapy technology. The advantages of dose homogeneity, steepness of dose gradient, and protection of normal organs are reflected in the treatment of head and neck cancers. We present the preliminary (2-year) clinical outcomes of HT in 85 patients with locally advanced NPC (LA-NPC). Of these patients, 3 patients (3.5%) experienced treatment interruption due to severe pulmonary infection, and 82 (96.5%) completed radiation treatments. The 2-year estimate of progression-free survival, local relapse-free survival, nodal relapse-free survival, distant metastases-free survival, and overall survival rate were 90%, 96.3%, 98.8%, 96.3%, and 96.3%, respectively. Among the three patients that died, one had stage III disease and died from fatal nasopharyngeal bleeding after radiotherapy, while the other two patients succumbed to local recurrence. Our experience suggests that HT can achieve promising disease control and survival in the treatment of LA-NPC patients with mild acute and late toxicity profiles.
摘要：
Syphilis is a chronic bacterial infection caused by Treponema pallidum (T pallidum) and the pathogenesis that T pallidum infection induces immunopathological damages in skin and other tissues remains unclear. We have previously reported that recombinant flagellins of T pallidum can elicit IL-6 and IL-8 transcriptions via TLR5 pathway. To identify the domains which induced the pro-inflammatory activity and the importance of the interactions between TLR5 and domains, homology-based modelling and comparative structural analyses revealed that Tpflagellins can combine with TLR5 directly. Deletion mutations showed that the ND1 domain binding to TLR5 is required but not sufficient in TLR5 activation. Moreover, site-directed mutagenesis analysis indicated that the arginine residue (Tpflagellins R89) of the ND1 domain and its adjacent residues (Tpflagellins L93 and E113) constitute a hot spot that elicits IL-6, IL-8 transcriptions and TLR5 activation, and affects the binding of Tpflagellins to TLR5. Taken together, these results give insight into the pathogenesis of T pallidum and may contribute to the future design of Tpflagellins-based therapeutics and syphilis vaccine.
作者机构：
[Xiao, Xiangsheng; Tang, Hailin; Xie, Xinhua; Xiao, XS; Xie, XM; Xie, Xiaoming; Liu, Peng; Zhang, Lijuan; Huang, Xiaojia] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Canc Ctr,Dept Breast Oncol, Guangzhou, Guangdong, Peoples R China.;[Chen, Bo] Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Canc Ctr, Dept Breast Canc, Guangzhou, Guangdong, Peoples R China.;[He, Rongfang] Univ South China, Affiliated Hosp 1, Dept Pathol, Hengyang, Hunan, Peoples R China.
通讯机构：
[Xiao, XS; Xie, XM] S;Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Canc Ctr,Dept Breast Oncol, Guangzhou, Guangdong, Peoples R China.
关键词：
SOX8;ZEB1;cancer stem cells;triple-negative breast cancer
摘要：
The molecular mechanisms underlying triple-negative breast cancer (TNBC) pathology are not fully understood. Here, we reviewed the SOX8 transcript level in 24 types of cancer and normal tissues and the SOX8 expression pattern in breast cancer from the TCGA and METABRIC data sets and found that SOX8 was highly expressed in TNBC. We investigated the effect of SOX8 on tumorigenicity, migration and apoptosis in TNBC cell lines and xenografts models. We identified SOX8 as a functional oncogene that involved in the maintenance of stem-like capacities in TNBC cells. Through a promoter truncation experiment and ChIP experiment, we verified zinc finger E-box binding homeobox 1 (ZEB1) as a transcriptional activator of SOX8 that enhanced SOX8 expression by binding to its promoter. We evaluated the ZEB1 and the SOX8 levels in 240 TNBC patients and high expression of ZEB1 and SOX8 were significantly associated with poor prognosis. We demonstrated the significance of the ZEB1-SOX8 axis in regulating TNBC cancer stem-like cells (CSCs) and its connection with poor prognosis. Due to its vital role in TNBC CSCs, the ZEB1-SOX8 regulatory axis could be a promising therapeutic target for TNBC.
摘要：
A biosorbent, 4-sulfonylcalix[6]arene modified Fe(3)O(4)@Aspergillus Niger (MFSC), was successfully prepared through a two-step route for the effective removal of uranium (U(VI)) from aqueous solutions with high selectivity. The structure of MFSC was characterized by FT-IR, SEM, XRD, TGA and VSM, respectively. The impacts of various experimental parameters were investigated in detail. The results indicated that the biosorption of U(VI) on MFSC was mainly attributed to the electrostatic attraction (91% within 8 hours for U(VI)). The adsorption kinetics and adsorption isotherm of U(VI) were found to follow the pseudo second-order model and to be fitted by the Langmuir model, respectively. The thermodynamic parameters revealed that the adsorption process was spontaneous and endothermic. The findings herein highlight the MFSC with high ability for removal of U(VI) from aqueous solutions.
通讯机构：
[Yin, WD; Tang, CK] U;Univ South China, Med Res Expt Ctr, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Cardiovasc Dis,Key Lab Arteriosclerol Hunan, Hengyang 421001, Hunan, Peoples R China.
关键词：
AS;CCDC80;DNA methylation;LPL;TET2
摘要：
Recent studies showed that coiled-coil domain-containing 80 (CCDC80) has a positive link with atherosclerosis and that plasma CCDC80 levels are positively correlated with the levels of fasting plasma triglycerides (TG) in obese individuals. The underlying mechanisms, however, are unclear. Using Hematoxylin-eosin (H&E) and Oil Red O staining, we found that CCDC80 overexpression in vivo significantly increased plasma lipid contents, decreased the expression and activity of lipoprotein lipase (LPL), and accelerated the development of atherosclerosis. Conversely, knockdown of CCDC80 decreased plaque lesions area. In vitro, qRT-PCR and western blot results showed that CCDC80 overexpression significantly decreased, while CCDC80 knockdown increased, LPL expression in cultured vascular smooth muscle cells (VSMCs). Further, we found that CCDC80 reduced LPL expression via inhibiting the phosphorylation of extracellular regulated protein kinase 1/2 (ERK1/2) and also increased the methylation of LPL promoter via down-regulating Tet methylcytosine dioxygenase 2 (TET2). Our results also revealed that CCDC80 significantly down-regulated TET2 expression through decreasing the phosphorylation of ERK1/2. In addition, we found that CCDC80 decreased binding of TET2 to forkhead box O3 (FOXO3a) but had no effect on FOXO3a expression. On the other hand, and that FOXO3a was partially involved in TET2-regulated LPL expression. CCDC80 down-regulated ERK1/2 phosphorylation and decreased expression of TET2 and its interaction with FOXO3a, leading to a reduction of LPL expression and acceleration of atherosclerosis.
作者机构：
[Li, Junyu] Canc Hosp Jiangxi Prov, Dept Radiotherapy, Nanchang 330029, Jiangxi, Peoples R China.;[Li, Yuehua; Wu, Xiaoping] Univ South China, Affiliated Hosp 1, Dept Med Oncol, Hengyang 421001, Hunan, Peoples R China.;[Li, Ying] Hubei Canc Hosp, Dept Radiat Oncol, 116 Zhuodaoquan South Rd, Wuhan 430079, Hubei, Peoples R China.
通讯机构：
[Li, Ying] H;Hubei Canc Hosp, Dept Radiat Oncol, 116 Zhuodaoquan South Rd, Wuhan 430079, Hubei, Peoples R China.
关键词：
biomarker;head and neck squamous cell carcinoma;long non-coding RNA;signature;survival
摘要：
Long non-coding RNAs (lncRNAs) are frequently dysregulated in cancer and their aberrant expression has been associated with cancer diagnosis and prognosis, which suggests that they may be promising molecular biomarkers. However, understanding of the expression pattern of lncRNAs and their prognostic roles in head and neck squamous cell carcinoma (HNSCC) is relatively limited. In the current study, the prognostic value of lncRNA expression profiles in predicting the OS of patients with HNSCC was investigated by integrating clinical and profiling data from The Cancer Genome Atlas. A total of ten lncRNAs closely associated with the prognosis of patients with HNSCC were identified and may serve as novel biomarkers. This 10-lncRNA signature was used to classify patients into 2 groups with significantly different overall survival (OS) times (median OS time, 1.65 vs. 13.04 years; P<0.0001). This lncRNA signature was validated in an independent testing cohort. The results of multivariable Cox regression and stratification analyses revealed that the prognostic value of the 10-lncRNA signature was independent of other clinical and pathological factors for the survival of patients with HNSCC. Functional analysis demonstrated that lncRNA expression-based risk scoring may reflect the basic status of the immune response in the tumor microenvironment. The presented study demonstrated the value of a lncRNA signature as a potential biomarker to improve the clinical prognosis of patients with HNSCC.
摘要：
Exposure to Mycoplasma pneumoniae leads to lung inflammation through a host defense pathway. Increasing evidence has indicated that the mycoplasma-derived membrane lipoprotein, or its analogue macrophage-activating lipopeptide-2 (MALP-2), excretes LPS as an immune system-stimulating substance and plays a crucial role in pathological injury during M. pneumoniae infection. It has been established that Sulforaphane confers anti-inflammatory properties. However, the underlying mechanism responsible for the inhibitory actions of Sulforaphane in the context of mycoplasmal pneumoniae are poorly understood. Here, we report that Sulforaphane is an inducer of heme oxygenase (HO)-1, a cytoprotective enzyme that catalyzes the degradation of heme through signaling pathways in human monocytes. Sulforaphane stimulated NF-E2-related factor 2 (Nrf2) translocation from the cytosol to the nucleus, and small interfering RNA-mediated knock-down of Nrf2 significantly inhibited Sulforaphane-induced HO-1 expression. Additionally, PI3K/Akt and ROS were also involved in Sulforaphane-induced Nrf2 activation and HO-1 expression, as revealed by the pharmacological inhibitors LY294002 and NAC. Moreover, Sulforaphane treatment inhibited MALP-2-induced pro-inflammatory cytokine secretion and pulmonary inflammation in mice, as well as MALP-2-triggered NF-kappaB activation. Furthermore, SnPP, a selective inhibitor of HO-1, reversed the inhibitory actions of Sulforaphane, while a carbon monoxide-releasing molecule, CORM-2, caused a significant decrease in MALP-2-induced cytokine secretion. Collectively, these results suggest that Sulforaphane functions as a suppressor of the MALP-2-induced inflammatory response, not only by inhibiting the expression of cytokines and the induction of HO-1 but also by diminishing NF-kappaB activation in cultured monocytes and the lungs of mice.
作者机构：
[Li, Jie; Tian, Shao-Wen; Chen, Fang-Ling] Univ South China, Dept Physiol, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.;[Wang, Bo] Univ South China, Affiliated Hosp 1, Dept Anesthesiol, Hengyang 421001, Hunan, Peoples R China.;[Tian, Shao-Wen] Guilin Med Univ, Guangxi Key Lab Brain & Cognit Neurosci, Guilin 541000, Guangxi, Peoples R China.;[Long, Chen] Cent S Univ, Xiangya Hosp 2, Dept Minimally Invas Surg, Changsha 410011, Hunan, Peoples R China.
通讯机构：
[Tian, Shao-Wen] U;[Long, Chen] C;Univ South China, Dept Physiol, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.;Cent S Univ, Xiangya Hosp 2, Dept Minimally Invas Surg, Changsha 410011, Hunan, Peoples R China.
关键词：
Apelin-13;Fear extinction;Memory;PTSD;Rats
摘要：
Fear extinction is considered as a new learning process that is valid to model features of post-traumatic stress disorder (PTSD). The neuropeptide apelin, such as apelin-13, apelin-17 and apelin-36, are endogenous ligands of the G-protein coupled receptor APJ. Apelin and its receptor APJ are widely distributed in the central nervous system. Accumulating evidence suggests the critical role of apelin-13 in modulation of learning and memory, however, its specific role in fear extinction remains unclear. In the present study, we investigated the effect of apelin-13 administration on contextual fear extinction in rats. The behavioral procedure included four sessions: habitation, conditioning, extinction training and extinction recall. Rats received intracerebroventricular infusion of apelin-13 (3 or 6 mu g) 0.5 h prior to the extinction training. Percentage of freezing was utilized to assess the conditioned fear response. Results showed that apelin-13, with the dose of 6 but not 3 mu g, significantly decreased freezing response during both extinction training and extinction recall test sessions. Furthermore, apelin-13 did not affect the levels of baseline freezing, locomotor activity and anxiety. The results suggest that apelin-13 dose-dependently enhances contextual fear extinction, and may function as a novel target for treatment of PTSD.
