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BACKGROUND: The intestinal barrier is the first line of defense against intestinal invasion by pathogens and foreign antigens and is closely associated with the gut microbiota. Astragalus polysaccharides (APS) have a long history of use in traditional Chinese medicine owing to its protective properties against intestinal barrier function. The mechanism of APS-induced gut microbiota enhancing intestinal barrier function is urgently needed. RESULTS: Dietary polysaccharide deprivation induced intestinal barrier dysfunction, decreased growth performance, altered microbial composition (Faecalibacterium, Dorea, and Coprobacillus), and reduced isobutyrate concentration. The results showed that APS facilitates intestinal barrier function in broiler chickens, including a thicker mucus layer, reduced crypt depth, and the growth of tight junction proteins. We studied the landscape of APS-induced gut microbiota and found that APS selectively promoted the growth of Parabacteroides, a commensal bacterium that plays a predominant role in enhancing intestinal barrier function. An in vitro growth assay further verified that APS selectively increased the abundance of Parabacteroides distasonis and Bacteroides uniformis. Dietary APS supplementation increased the concentrations of isobutyrate and bile acid (mainly chenodeoxycholic acid and deoxycholate acid) and activated signaling pathways related to intestinal barrier function (such as protein processing in the endoplasmic reticulum, tight junctions, and adherens junction signaling pathways). CONCLUSIONS: APS intervention restored the dietary polysaccharide-induced dysfunction of the intestinal barrier by selectively promoting the abundance of Parabacteroides distasonis, and increasing the concentrations of isobutyrate and bile acids (mainly CDCA and DCA). These findings suggest that APS-induced gut microbiota and metabolic niches are promising strategies for enhancing intestinal barrier function.
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IMPORTANCE: The intestinal mucus barrier, located at the interface of the intestinal epithelium and the microbiota, is the first line of defense against pathogenic microorganisms and environmental antigens. Dietary polysaccharides, which act as microbiota-accessible fiber, play a key role in the regulation of intestinal microbial communities. However, the mechanism via which dietary fiber affects the intestinal mucus barrier through targeted regulation of the gut microbiota is not clear. This study provides fundamental evidence for the benefits of dietary fiber supplementation in broiler chickens through improvement in the intestinal mucus barrier by targeted regulation of the gut ecosystem. Our findings suggest that the microbiota-accessible fiber-gut microbiota-short-chain fatty acid/bile acid axis plays a key role in regulating intestinal function.
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Pollos , Microbiota , Animales , Fibras de la Dieta , Ácidos Grasos Volátiles/metabolismo , Moco/metabolismo , Ácidos y Sales BiliaresRESUMEN
Previous studies mainly focus on the game analysis of green building development under carbon tax policy, while carbon trading, as one of the important means to promote low-carbon development, is rarely mentioned in promoting the development of the green building market. Based on this, to study the impact of carbon trading policy on the development of the green building market, this study combines prospect theory for carbon trading to build a three-way evolutionary game model of developer-government-consumer. It studies the influencing causes of green building market development under the carbon trading mechanism from the whole perspective. The study shows the existence of a carbon trading policy helps the development of the green building market. In the presence of a carbon trading market, the government's punishment, subsidies, and the setting of carbon prices influence the development of the green building market. In addition, the percentage of carbon emissions bought, the potential benefits, and the selling price also affect the chance of consumers buying green buildings to a greater or lesser extent. This study introduces prospect theory into the developer-government-consumer three-way evolutionary game model, which enriches the research perspective of each subject's behavior in the green building market. It provides theoretical support for developers, governments, and consumers to collaborate to promote the coordination and development of the green building market. It has policy implications for promoting the green and high-quality development of the construction industry.
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Carbono , Industria de la Construcción , Carbono/análisis , Simulación por Computador , Políticas , Comportamiento del Consumidor , ChinaRESUMEN
The prevalence and transmission of vancomycin-resistant Enterococcus (VRE) in enterococci being as probiotics has been neglected in the scientific literature. The application of enterococci in feed, food and health products may cause VRE transmission through the food chain. This study evaluated phenotypic resistance of Enterococcus species to 20 antibiotics along a pork production chain from feed to food. It also assessed the genetic diversity of Enterococcus faecium isolates. A total of 510 samples (feed, n = 70; swine manure, n = 400; swine carcasses, n = 20, and retail pork, n = 20) were collected in Beijing, China. A total of 328 enterococci isolates with 275 E. faecium and 53 Enterococcus faecalis were identified using 16 S rRNA. Antimicrobial susceptibility to all enterococci isolates was conducted using the K-B method for 20 antibiotics from 9 categories. Multilocus sequence typing (MLST) was conducted on the E. faecium isolates to survey the dissemination of enterococci in the pig industry. The results showed that only 26 enterococci isolates were sensitive to the 20 antibiotics, while half of the isolates (164/328) had acquired multi-drug resistance. The resistant rate to furazolidone was 68.60%, followed by 42.99% to tetracycline. One vancomycin-resistant E. faecium isolates were isolated from feed origin and 2 from manure origin, with minimum inhibitory concentrations to vancomycin of 1,024, 64, and 64 µg/mL, respectively. The MLST outcomes showed that the 275 E. faecium isolates belonged to 11 sequence types (ST) including ST40, ST60, ST94, ST160, ST178, ST296, ST361, ST695, ST726, ST812 and ST1014. The ST of the feed-sourced VRE was ST1014, while the 2 manure-sourced VRE was ST69. ST1014 evolved from ST78, which was the dominant clonal complex in most cities of China, leading to the spreading of VRE. These findings revealed the potential safety hazards of commercial probiotic enterococci in China and showed that there is a risk of the VRE horizontally transferring from feed to food.
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Contextual information has been shown to be powerful for semantic segmentation. This work proposes a novel Context-based Tandem Network (CTNet) by interactively exploring the spatial contextual information and the channel contextual information, which can discover the semantic context for semantic segmentation. Specifically, the Spatial Contextual Module (SCM) is leveraged to uncover the spatial contextual dependency between pixels by exploring the correlation between pixels and categories. Meanwhile, the Channel Contextual Module (CCM) is introduced to learn the semantic features including the semantic feature maps and class-specific features by modeling the long-term semantic dependence between channels. The learned semantic features are utilized as the prior knowledge to guide the learning of SCM, which can make SCM obtain more accurate long-range spatial dependency. Finally, to further improve the performance of the learned representations for semantic segmentation, the results of the two context modules are adaptively integrated to achieve better results. Extensive experiments are conducted on four widely-used datasets, i.e., PASCAL-Context, Cityscapes, ADE20K and PASCAL VOC2012. The results demonstrate the superior performance of the proposed CTNet by comparison with several state-of-the-art methods. The source code and models are available at https://github.com/syp2ysy/CTNet.
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At night, visual quality is reduced due to insufficient illumination so that it is difficult to conduct high-level visual tasks effectively. Existing image enhancement methods only focus on brightness improvement, however, improving image quality in low-light environments still remains a challenging task. In order to overcome the limitations of existing enhancement algorithms with insufficient enhancement, a progressive two-stage image enhancement network is proposed in this paper. The low-light image enhancement problem is innovatively divided into two stages. The first stage of the network extracts the multi-scale features of the image through an encoder and decoder structure. The second stage of the network refines the results after enhancement to further improve output brightness. Experimental results and data analysis show that our method can achieve state-of-the-art performance on synthetic and real data sets, with both subjective and objective capability superior to other approaches.
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ABSTRACT: The purpose of this study was to investigate the mediating effects of self-acceptance on loneliness and subjective well-being (SWB) among elderly subjects living in Chinese nursing homes.This cross-sectional study was conducted between October 2019 and March 2020. A total of 415 elderly participants aged 60 to 97 years (mean 81.12â±â8.90âyears) from 3 medical and nursing homes in Fuyang city, Anhui province, were selected using a convenience sampling method. Data were collected using a general information questionnaire, the Memorial University of Newfoundland Scale of Happiness, the self-acceptance scale, and the UCLA Loneliness scale. Correlations, regressions, and structural equation models were used for the analyses. Multiple linear regression analysis was performed to confirm the factors influencing the SWB. Bootstrapping was performed to confirm the mediation effect.The loneliness of elderly subjects in nursing homes was significantly correlated with self-acceptance and SWB (râ=â-0.338, Pâ<â.01; râ=â-0.383, Pâ<â.01), and self-acceptance was significantly correlated with SWB (râ=â0.401, Pâ<â.01). Multiple linear regression revealed that the relationship with children, loneliness, residence time in nursing homes, income, marital status, self-acceptance, original residence, and frequency of children's visits were the main factors affecting SWB. Bootstrapping showed that the mediating role of self-acceptance was statistically significant.The SWB of elderly individuals living in Chinese nursing homes was moderate. Low-income people, subjects from rural areas, and those newly admitted to nursing homes should be emphasized in interventions, and appropriate measures should be taken to harmonize the relationships between elderly residents and their children. Self-acceptance partially mediated the relationship between loneliness and SWB. Consequently, self-acceptance should be the focus of improving the SWB of elderly nursing home residents.
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Soledad/psicología , Satisfacción Personal , Anciano , Anciano de 80 o más Años , China , Estudios Transversales , Femenino , Hogares para Ancianos/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Casas de Salud/estadística & datos numéricos , Calidad de Vida , Encuestas y CuestionariosRESUMEN
As one of the most severe kinds of neurological damage, spinal cord injury (SCI) contributes to persistent motor dysfunction and involves a large repertoire of gene alterations. The participation of circular RNAs (circRNAs) in neurological recovery following SCI needs to be clarified. In the current work, we attempted to assess the function of hsa_circRNA_0003962/circTYW1 and its underlying mechanism in SCI. By accessing the GEO repository, the expression of circTYW1, microRNA-380 (miR-380), and FGF9 in SCI and sham-operated rats was evaluated. PC12 cells after oxygen-glucose deprivation (OGD) treatment were prepared to mimic the SCI model. circTYW1 and FGF9 were poorly expressed, whereas miR-380 was highly expressed in the spinal cord tissues of SCI rats. circTYW1 promoted neurological recovery in SCI rats and inhibited apoptosis in spinal cord tissues. In PC12 cells exposed to OGD, circTYW1 suppressed PC12 cell apoptosis; however, miR-380 overexpression reversed the protective effect of circTYW1 on PC12 cells. Also, circTYW1 promoted FGF9 expression through competitively binding to miR-380, which activated the ERK1/2 signaling. In summary, our results demonstrated that declines in circTYW1 prevented SCI rats from neurological recovery by regulating the miR-380/FGF9/ERK1/2 axis, which might provide new understanding for SCI treatment.
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Factor 9 de Crecimiento de Fibroblastos/metabolismo , Sistema de Señalización de MAP Quinasas/genética , MicroARNs/metabolismo , Neuronas/metabolismo , ARN Circular/metabolismo , Recuperación de la Función/genética , Traumatismos de la Médula Espinal/metabolismo , Animales , Apoptosis/genética , Hipoxia de la Célula/genética , Modelos Animales de Enfermedad , Factor 9 de Crecimiento de Fibroblastos/genética , Glucosa/metabolismo , Masculino , MicroARNs/genética , Células PC12 , ARN Circular/genética , Ratas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/genética , TransfecciónRESUMEN
Objective: This study was conducted to determine whether regulatory T cells (CD4+CD25+T, Tregs) show abnormal mitophagy as well as the function of Tregs in patients with myasthenia gravis (MG). Methods: CD4+T cells and CD4+CD25+Treg cells were obtained from 15 patients with MG (MG group) and 15 controls (N group). Tregs from the MG group were subjected to rapamycin-induced culture for 48 h (Rapa group) and 3-methyladenine-induced culture for 48 h (3-MA group). The levels of mitophagy in Tregs were then observed through electron and confocal microscopy. Expression of the autophagy-related protein LC3-II was detected by western blotting, and mitochondrial function in each group was evaluated by flow cytometry. Inhibition of Treg cell proliferation was detected by flow cytometry. Results: Mitophagy in the MG group was lower than that in the N group; it was higher in the Rapa group compared to that in the MG group and lowered in the 3-MA group than in the MG group. Expression of the autophagy-related protein LC3-II was lower in the MG group than in the N group, higher in the Rapa group than in the MG group, and lower in the 3-MA group than in the MG group. The mitochondrial membrane potential was lower in the MG group compared to that in the N group; it was higher in the Rapa group than in the MG group and lowered in the 3-MA group than in the MG group. Inhibition of Treg proliferation was lower in the MG group than in the N group; it was higher in the Rapa group than in the MG group and lowered in the 3-MA group than in the MG group. Conclusion: The decreased mitochondrial membrane potential and mitophagy in Tregs in the MG group may be related to a decreased inhibition of Treg proliferation. The mitochondrial membrane potential was increased after adding the autophagy agent Rapa to enhance mitophagy, and the proliferation inhibition function of Tregs was also enhanced. The autophagy agent 3-MA down-regulated mitophagy, which decreased the mitochondrial membrane potential and inhibitory effect of Tregs. These results reveal the possible cellular immune mechanism of Treg dysfunction in MG.
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Enzymatic decomposition of extracellular matrix and possibly local inflammation may cause intervertebral disc degeneration (IDD). MicroRNAs have been reported to correlate with the development of IDD. In this experiment, we aim at finding out the role of miR-181a in the inflammation of IDD and the underlying mechanism. The targeting relationship between miR-181a and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was verified. Following the establishment of IDD mouse models, disc height index (DHI) and the change of DHI (%DHI) were measured. The functional role of miR-181a in IDD was determined using ectopic expression and depletion and reporter assay experiments. Expression of miR-181a, TRAIL, extracellular signal-regulated kinase (ERK) pathway-related genes and inflammatory factors was evaluated. Also, the expression of collagen I and collagen II was observed. miR-181a directly targeted TRAIL. IDD mice exhibited significant degeneration of the intervertebral disc. miR-181a was downregulated while TRAIL was upregulated in mice with IDD. miR-181a upregulation and the ERK pathway inhibition could reduce expression of TRAIL, ERK pathway-related genes, inflammatory factors, and collagen I, but promote collagen II expression. Our results reveal that upregulation of miR-181a protects against inflammatory response by inactivating the ERK pathway via suppression of TRAIL in IDD mice. These results point to miR-181a as a potential therapeutic target for the clinical management of IDD.
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Antiinflamatorios/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Degeneración del Disco Intervertebral/patología , MicroARNs/genética , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Animales , Colágeno/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/genética , Disco Intervertebral/patología , Dolor de la Región Lumbar/etiología , Sistema de Señalización de MAP Quinasas/genética , RatonesRESUMEN
Osteoblastic bone formation is important for maintaining the balance of bone turnover. However, the underlying mechanisms are still needed to be elucidated. Histamine H1 type receptor (H1R) is a major subtype of histamine membrane receptors family, which has displayed diverse biological functions in various tissues and cells. In the current study, we have identified a novel physiological function of H1R in regulating osteoblastic differentiation and mineralization of the MC3T3-E1 cells. We found that H1R is expressed in the MC3T3-E1 cells. Interestingly, H1R is up-regulated in the process of differentiation and mineralization of the MC3T3-E1cells induced by osteogenic medium (OM). Blockage of H1R using its specific antagonist Loratadine prevented differentiation and mineralization of the MC3T3-E1 cells by reducing ALP activity, bone matrix deposition, and the expressions of osteogenic marker genes including ALP, OCN, Osx, and type I collagen as well as the transcriptional factor RUNX-2, which is a central regulator of osteoblastogenesis. In contrast, we found that activation of H1R with Histamine exerts opposite actions by increasing the expressions of RUNX-2. Finally, we found that the effects of H1R in osteoblastic differentiation and mineralization are mediated by the AMPK/eNOS signaling. Based on these findings, we concluded that H1R might be an important therapeutic target for the treatment of skeletal disorders.
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Diferenciación Celular , Minerales/metabolismo , Osteoblastos/citología , Osteoblastos/metabolismo , Receptores Histamínicos H1/metabolismo , Células 3T3 , Animales , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Ratones , Óxido Nítrico/metabolismo , OsteogénesisRESUMEN
Apoptosis acts as the primary pathogenesis of cerebral ischemia/reperfusion (I/R) injury. Prior studies have revealed the effects of src homology 2 (SH2)B adaptor protein 1 (SH2B1) in myocardial infarction; however, involvement of SH2B1 in cerebral I/R injury and the underlying mechanisms remain to be investigated. In the present study, neurallike PC12 cells underwent 6 h of oxygenglucose deprivation (OGD) followed by 24 h of reoxygenation (OGD/R). PC12 cells were pretransfected with an adenovirus encoding for SH2B1 or GFP prior to exposure to OGD/R. Cell viability, LDH release and the apoptotic cascade were investigated. Reverse transcriptionquantitative polymerase chain reaction and western blotting were employed to analyze mRNA and protein expression levels, respectively. The results of the present study revealed that OGD/R reduced SH2B1 expression in PC12 cells, accompanied by suppressed cell viability and enhanced cell death. Adenovirusmediated SH2B1 overexpression, however, resulted in increased viability, reduced LDH release and a reduction in the expression levels of proteins associated with the apoptotic cascade in PC12 cells under the OGD/R condition. A mechanistic explanation may be that the positive effects of SH2B1 on neurons were in part derived from the activation of the JAK2/STAT3 signaling pathway. Furthermore, abolishment of JAK2/STAT3 signaling using a pharmacological inhibitor suppressed the inhibitory effects of SH2B1 under the OGD/R condition. The results of the present study suggested that SH2B1 may protect PC12 cells from OGD/R injury partially by the JAK2/STAT3dependent inhibition of apoptosis and may provide a novel therapeutic target for the treatment of cerebral I/R injury.
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Proteínas Portadoras/metabolismo , Hipoxia de la Célula , Janus Quinasa 2/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Animales , Apoptosis , Proteínas Portadoras/genética , Caspasa 3/metabolismo , Supervivencia Celular , Regulación hacia Abajo , Glucosa/metabolismo , Péptidos y Proteínas de Señalización Intracelular , L-Lactato Deshidrogenasa/metabolismo , Células PC12 , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Radioprotective 105 kDa protein (RP105) has been reported to produce favorable outcomes in various cardiovascular disorders via a tolllike receptor 4dependent or independent manner. However, whether RP105 exerts neuroprotective effects against oxygenglucose deprivation (OGD)/reoxygenation (OGD/R) injury remains to be elucidated. In the present study, the PC12 neuronal cell line was exposed to 4 h of OGD followed by 24 h of reoxygenation. Adenoviral vectors encoding RP105 were utilized to upregulate the level of RP105 in PC12 cells prior to OGD/R induction. The results demonstrated that OGD/R reduced the expression of RP105 at the mRNA and protein levels. The overexpression of RP105 significantly reversed OGD/Rinduced neuronal injuries, as demonstrated by the reduced release of lactate dehydrogenate and enhanced cellular viability, in addition to decreased inflammation, apoptosis and reactive oxygen species. The mechanistic evaluations indicated that the neuroprotective functions of RP105 were, in part, a result of activation of the phosphatidylinositol 3kinase (PI3K)/protein kinase B (AKT) pathway. In addition, elimination of the PI3K/AKT axis via the use of a pharmacological inhibitor inhibited the OGD/Rinhibitory effects induced by the overexpression of RP105. Taken together, RP105 protected PC12 cells from OGD/R injury through promotion of the PI3K/AKT pathway; therefore, the RP105PI3KAKT axis may provide a novel therapeutic target for the prevention of cerebral ischemia/reperfusion injury.
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Antígenos CD/metabolismo , Glucosa/metabolismo , Neuronas/citología , Oxígeno/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Supervivencia Celular , Neuronas/metabolismo , Neuroprotección , Células PC12 , Ratas , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/metabolismo , Transducción de SeñalRESUMEN
Osteosarcoma is the most common primary malignant bone tumor in the pediatric age group, and chemotherapy directed by targeted nanoparticulate drug delivery system represents a promising approach for osteosarcoma treatment recently. Here, we designed and developed a novel DOX-loaded targeted polymeric micelle self-assembled from RGD-terminated poly(ethylene glycol)-block-poly (trimethylene carbonate) (RGD-PEG-PTMC) amphiphilic biodegradable block copolymer, for high-efficiency targeted chemotherapy of osteosarcoma. Notably, the RGD-installed DOX-loaded biodegradable polymeric micelle (RGD-DOX-PM) with drug loading efficiency of 57%-73% displayed a narrow distribution (PDI=0.05-0.12) with average sizes ranging from 46 to 73nm depending on the DOX loading content. The release amount of DOX from RGD-DOX-PM achieved 63% within 60h under physiological condition. Interestingly, MTT assays in MG-63 and MNNG/HOS osteosarcoma cells exhibited that half-maximal inhibitory concentration (IC50) value of RGD-DOX-PM was much lower than its non-targeted counterpart (DOX-PM), implying RGD decorated nanoparticles had enhanced cell targeting ability and led to more effective anti-tumor effect. Furthermore, the targeting ability of RGD-DOX-PM was confirmed by in vitro flow cytometry and confocal laser scanning microscopy (CLSM) imaging assays, where the results showed more RGD-DOX-PM were taken up by MG-63 cells than that of DOX-PM. Therefore, this RGD decorated DOX-loaded polymeric micelle is promising for targeted chemotherapy of osteosarcoma.
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Antineoplásicos/farmacología , Dioxanos/química , Doxorrubicina/farmacología , Oligopéptidos/química , Osteosarcoma/tratamiento farmacológico , Polietilenglicoles/química , Polímeros/química , Antineoplásicos/química , Línea Celular Tumoral , Doxorrubicina/química , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Humanos , Micelas , Estructura Molecular , Osteoblastos/efectos de los fármacosRESUMEN
OBJECTIVE: Normothermic blood perfusion is the developing trend of donor heart preservation. Theoretically, donor hearts preserved in a beating status may be the perfect method to reduce time-dependent ischemic injury, resuscitate marginal hearts expanding the donor pool and potentially improve the function of isolated hearts. In this study, to investigate the protective effect of normothermic blood perfusion, we maintained the donor hearts in a beating status and compared the changes of myocardial apoptosis and injury with standard hypothermic and static storage. METHODS: Thirty rat hearts were preserved in static cold storage (Group A, n=10, stored in 4°C histidine-tryptophan-ketoglutarate solution), or in static normothermic blood perfusion (Group B, n=10, perfused with normothermic blood) or in beating status (Group C, n=10, perfused continuously with normothermic blood) for 9 hours. Myocardial injury markers including creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI), myocardial metabolic rate related indicators including Methane Dicarboxylic Aldehyde (MDA) and Adenosine Triphosphate (ATP) were investigated before and after preservation. And also TUNEL staining and mRNA and protein expression of apoptosis markers such as Bax, Bcl-2, Caspase-3 and Cleaved Caspase-3 were used to evaluated the degree of myocardial apoptosis. RESULTS: It is found that the levels of CK-MB and cTnI in Group C were significantly lower than those of Group A and Group B (P<0.05). However, there was no significant statistical difference of ATP content among three groups. When compared with Group A and B, the quality of MDA in Group C was obviously lower. In addition, it showed that a remarkable reduction in TUNEL-positive nuclear staining in Group C but higher in other two groups. And inhibited apoptosis was also confirmed by the results of mRNA and protein expression of apoptosis markers including Bax and Bcl-2. CONCLUSIONS: It is an effective and appropriate approach to preserve donor hearts with continuous and normothermic blood perfusion as to keep them in beating status in heart transplantation, which could reduce myocardial ischemic damage and cardiac apoptosis in long-term preservation.