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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which multiple organs are damaged that prevails in fertile women. Currently, glucocorticoids and immunosuppressants are widely used to treat SLE patients. However, ovarian dysfunction occurs following the use of these drugs in women with SLE. Here, we summarize recent progress in terms of understanding ovarian injury, the effects of drug application and strategies to improve ovarian function in women with SLE. This review could be helpful to precisely cure SLE in women desiring to have offspring.
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Objective: To explore the genotyping characteristics of human fecal Escherichia coli( E. coli) and the relationships between antibiotic resistance genes (ARGs) and multidrug resistance (MDR) of E. coli in Miyun District, Beijing, an area with high incidence of infectious diarrheal cases but no related data. Methods: Over a period of 3 years, 94 E. coli strains were isolated from fecal samples collected from Miyun District Hospital, a surveillance hospital of the National Pathogen Identification Network. The antibiotic susceptibility of the isolates was determined by the broth microdilution method. ARGs, multilocus sequence typing (MLST), and polymorphism trees were analyzed using whole-genome sequencing data (WGS). Results: This study revealed that 68.09% of the isolates had MDR, prevalent and distributed in different clades, with a relatively high rate and low pathogenicity. There was no difference in MDR between the diarrheal (49/70) and healthy groups (15/24). Conclusion: We developed a random forest (RF) prediction model of TEM.1 + baeR + mphA + mphB + QnrS1 + AAC.3-IId to identify MDR status, highlighting its potential for early resistance identification. The causes of MDR are likely mobile units transmitting the ARGs. In the future, we will continue to strengthen the monitoring of ARGs and MDR, and increase the number of strains to further verify the accuracy of the MDR markers.
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Infecções por Escherichia coli , Escherichia coli , Humanos , Escherichia coli/genética , Infecções por Escherichia coli/epidemiologia , Tipagem de Sequências Multilocus , Genótipo , Pequim , Farmacorresistência Bacteriana Múltipla/genética , Antibacterianos/farmacologia , Diarreia , Testes de Sensibilidade MicrobianaRESUMO
In this study, molecularly imprinted polymers (MIPs) were assembled on the surface of ethylene imine polymer (PEI)/poly(vinyl alcohol) (PVA) electrospun nanofiber membranes for the point-of-care testing (POCT) of thiodiglycol (TDG), a sulfur mustard poisoning metabolic marker, using concentrated gold nanoparticles (AuNPs) as the signal reporting units. The MIPs/PEI/PVA nanofiber membranes could capture TDG specifically through the recognition interaction between MIPs and TDG. Then, AuNPs were adsorbed onto the MIPs/PEI/PVA nanofiber membranes through the Au-S interaction between TDG and AuNPs to produce a visible red color. In order to improve the sensitivity, the silver-enhanced solutions were used to deepen the color of the nanofiber membranes and the software Image J was used to read the gray value as the signal response for subsequent analysis. There was a good linear relationship between the color change of the MIPs/PEI/PVA nanofiber membranes and the TDG concentration from 0.1 ng mL-1 to 1.0 µg mL-1, and the limit of detection was 38 pg mL-1. This method was applied for the selective detection of TDG in urine, showing great potential for the clinical diagnosis of mustard gas poisoning.
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Nanopartículas Metálicas , Gás de Mostarda , Nanofibras , Polímeros Molecularmente Impressos , Ouro , Sistemas Automatizados de Assistência Junto ao Leito , Eletricidade EstáticaRESUMO
Natural products are a rich resource for discovering innovational drugs. Herein, we isolated and characterized two compounds dihydroalterperylenol (DAP) and alterperylenol (AP) from Alternaria sp. MG1, an endophytic fungus isolated from Vitis quinquangularis, and investigated the underlying antitumor mechanism of AP. Mechanistically, AP inhibits the growth of HepG2 cells by targeting the selenoprotein thioredoxin reductase (TrxR) and ultimately induces cell apoptosis and ferroptosis. Compared to DAP, the α,ß-unsaturated carbonyl structure of AP is an indispensable moiety for its antitumor activity and TrxR inhibition. Specifically, inhibition of TrxR causes the extensive reactive oxygen species and consequently results in DNA damage, G2/M cell cycle arrest, and mitochondrial fission. Furthermore, ferroptosis is driven via excess toxic lipid peroxidation and elevation of intracellular iron levels via regulating iron-related proteins. In vivo validation also shows that AP owns anticancer activity in xenograft mice. Collectively, our results disclose a novel natural TrxR inhibitor AP exerting the antitumor effect via inducing cell apoptosis and ferroptosis and evidence that AP is a promising candidate agent for liver carcinoma therapy. The link of TrxR inhibition to ferroptosis further highlights the physiological importance of TrxR in regulating ferroptosis.
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Antineoplásicos , Ferroptose , Neoplasias Hepáticas , Humanos , Camundongos , Animais , Tiorredoxina Dissulfeto Redutase/genética , Tiorredoxina Dissulfeto Redutase/metabolismo , Apoptose , Espécies Reativas de Oxigênio/metabolismo , Inibidores Enzimáticos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Antineoplásicos/químicaRESUMO
Objective: To improve the level of clinical diagnosis and treatment, reduce the incidence of complications, and provide the basis for clinicians to choose an appropriate treatment, this research explores the removal methods of the impacted denture in the esophagus by endoscopy. Methods: Based on the clinical information, treatment methods and complications of 72 patients with denture impaction in the esophagus admitted to our hospital from January 2016 to March 2021, which were divided into the group treated with painless endoscopy and the group treated with conventional endoscopy, retrospective analysis of the therapeutic effect and complications was conducted. Results: There was no statistically significant difference between the two groups in terms of denture removal rate (P > 0.05). There were statistically significant differences between the two groups in terms of operating time and incidence rates of complications during and after the procedure. The operating time of the group treated with painless endoscopy was significantly shorter than the group treated with conventional endoscopy (P < 0.05). The incidence rates of complications during and after the procedure of the group treated with painless endoscopy were significantly lower than the group treated with conventional endoscopy (P < 0.05). Conclusions: Compared with the conventional endoscopy, painless endoscopic management of denture impaction in the esophagus under general anesthesia with tracheal intubation improves the clinical efficacy and reduces the adverse reactions. Thus, it is worthy of clinical popularization and application.
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Corpos Estranhos , Dentaduras/efeitos adversos , Endoscopia , Esôfago , Corpos Estranhos/complicações , Corpos Estranhos/diagnóstico , Humanos , Estudos RetrospectivosRESUMO
Staphylococcal enterotoxin B (SEB) is a typical biological toxin that causes food poisoning. Currently reported SEB detection methods have the drawbacks of sophisticated sample preparation and being time-consuming and labor-intensive. Herein, we propose a strategy based on an immune sandwich structure operating on a centrifugal microfluidic chip for point-of-care testing (POCT) of SEB. The fluorescent microparticle-labeled primary antibody (CM-EUs-Ab1), capture antibody (CAb), and goat anti-mouse IgG antibody (SAb) were modified on the bond area, T-area, and C-area, respectively. When SEB was added, it first reacted with the CM-EUs-Ab1 through the specific recognition between SEB and the Ab1. Then, under capillarity, the conjugates of SEB and the CM-EUs-Ab1 were captured by the CAb when they flowed to the T-area, and the remaining CM-EUs-Ab1 bound with the SAb in the C-area. Finally, this chip was put into a dry fluorescence detection analyzer for centrifugation and on-site detection of SEB. The fluorescence intensity ratio of the T-area to the C-area was positively correlated with the concentration of SEB. The resulting linear range was 0.1-250 ng mL-1, and the limit of detection (3σ/k) was 68 pg mL-1. This POCT platform only needs 20 µL of sample and can realize the full process of detection within 12 min. This chip also exhibits good stability for 35 days. Additionally, the proposed method has been successfully utilized for the detection of SEB in urine, milk, and juice without any pre-treatment of the samples. Thus, this platform is expected to be applied to food safety testing and clinical diagnosis.
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Contaminação de Alimentos , Microfluídica , Animais , Enterotoxinas/análise , Contaminação de Alimentos/análise , Camundongos , Testes ImediatosRESUMO
OBJECTIVE: To study the effects of adaptive response in A549 cells induced by low-dose radiation and the miRNAs expression. METHODS: A549 cells were irradiated with 50 mGy and 200 mGy initial doses, respectively, and then irradiated with a challenge dose 20 Gy at 6 hours interval. The biological effects and miRNA expression were detected. RESULTS: The apoptosis rates of 50 mGy-20 Gy and 200 mGy-20 Gy groups were significantly lower than that of only 20 Gy irradiation group (P < .05). The percentage of G2/M phase cells of 50 mGy-20 Gy and 200 mGy-20 Gy groups was significantly decreased relative to the 20 Gy group (P < .05). One miRNA (mir-3662) was upregulated and 15 miRNAs (mir-185, mir-1908, mir-307, mir-182, mir-92a, mir-582, mi-r501, mir138-5p, mir-1260, mir-484, mir-378d, mir-193b, mir-127-3p, mir-1303, and mir-654-5p) were downregulated both in 50 mGy-20 Gy and 200 mGy-20 Gy groups than that of the 20 Gy group. Go and KEGG enrichment analysis showed that the target genes were significantly enriched in cell communication regulation, metabolic process, enzyme binding, and catalytic activity signaling pathways. CONCLUSION: Low-dose X-ray of 50 mGy and 200 mGy radiation can induce adaptive apoptosis response prior to 20 Gy in A549 cells. Sixteen differently expressed miRNAs may play important roles in the adaptive effect of low-dose radiation.
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Clonorosins A (1) and B (2), two novel indole alkaloids featuring unprecedented 6/5/6/6/5 and 6/5/5 cores, together with seven known indole-linked 2,5-diketopiperazine alkaloids (3-9), were isolated from the soil-derived fungus Clonostachys rosea YRS-06. The new structures were proposed through HR-MS, NMR, and ECD spectroscopic data. They were established by comparing the calculated NMR, ECD, and specific rotation data with the experimental. To assist in determining the absolute configuration of the chiral carbon in the side chain of 2,5-diketopiperazine derivatives, flexible analogues 3i-3iv were synthesized and analyzed. 1 was active against Fusarium oxysporum with an MIC value of 50 µg/mL. 7 and 8 showed excellent activity against human HeLa and HepG2 cells with IC50 values of 0.12-0.60 µM.
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Antibacterianos/farmacologia , Hypocreales/química , Alcaloides Indólicos/farmacologia , Antibacterianos/isolamento & purificação , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Células HeLa , Células Hep G2 , Humanos , Alcaloides Indólicos/isolamento & purificação , Estrutura Molecular , Microbiologia do SoloRESUMO
Six new polyketides, alternaritins A-D [(±)-1-4] and isoxanalteric acid I (8), and 25 known Alternaria toxins were isolated from the culture of an endophytic fungi Alternaria sp. MG1. 3 is a rare fungal metabolite. 6 is a new natural product, and 5, 7, and 9 are known previously but their absolute configurations have not been determined. Three enantiomers [(±)-1, (±)-7, and (±)-15] were separated via chiral HPLC resolution. The structures of those polyketides (1-9) were elucidated by spectrometric analysis using MS and NMR. The absolute configurations were established using X-ray diffraction analysis and statistical comparative analysis of the experimental ECD and OR data, in conjunction with quantum mechanical calculations. All of the compounds were evaluated for their bioactivities. Known compound 27 exerted the most potent cytotoxic activities against HT-1080 and NCI-H1299 cell lines. The new compounds, 2 and 3, showed moderate inhibition on COX-2, while a pair of isomers, 8 and 9, exhibited medium activity on COX-2 and uropathogenic Escherichia coli.
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Alternaria/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Policetídeos/farmacologia , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos/isolamento & purificação , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Inibidores de Ciclo-Oxigenase 2/isolamento & purificação , Inibidores de Ciclo-Oxigenase 2/farmacologia , Endófitos/química , Humanos , Estrutura Molecular , Policetídeos/isolamento & purificação , Estereoisomerismo , Escherichia coli Uropatogênica/efeitos dos fármacos , Vitis/microbiologiaRESUMO
Protein is an excellent molecular mass amplifier without fluorescence quenching effect for fluorescence anisotropy (FA) assay. However, in traditional protein amplified FA methods, the binding ratio between amplifier and dye-modified probe is 1:1 or one target can only induce FA change of one fluorophore on probe, resulting in low sensitivity. Herein, we developed a simple FA strategy with high accuracy and sensitivity by using a crosslinked submicro-hydrogel that was formed through a catalyzed hairpin assembly (CHA) assisted protein aggregation as a novel FA amplifier. In the presence of catalyst, the CHA process was initiated through the toehold-mediated strand exchange reaction, which led to the formation of a dye and biotin-labeled Y-shaped H1-H2 duplex (YHD) and recycling of catalyst. With the introduction of streptavidin, a crosslinked submicro-hydrogel was formed by strong binding affinity between biotin on YHD and streptavidin, resulting in an increased FA of fluorescent dye. After rational design of the catalyst sequence, this method has been utilized for the detection of miRNA-145, staphylococcal enterotoxin B (SEB) and ATP with an LOD of 2.5 nM, 92 pg mL-1 and 3.6 µM, respectively. Moreover, this FA assay has been successfully applied for direct detection of target in biological samples, demonstrating its practicality in complex biological systems.
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Técnicas Biossensoriais , Agregados Proteicos , DNA , Polarização de Fluorescência , Hidrogéis , Limite de DetecçãoRESUMO
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD), an autoimmune astrocytopathic disease associated with the anti-aquaporin-4 (AQP4) antibody, is characterized by extensive necrotic lesions primarily located on the optic nerves and spinal cord. Tanshinone IIA (TSA), an active natural compound extracted from Salvia miltiorrhiza Bunge, has profound immunosuppressive effects on neutrophils. OBJECTIVE: The present study aimed to evaluate the effect of TSA on NMOSD mice and explore the underlying mechanisms. Mice were initially administered TSA (pre-TSA group, n = 20) or vehicle (vehicle group, n = 20) every 8 h for 3 days, and then NMOSD model was induced by intracerebral injection of NMOSD-immunoglobulin G (NMO-IgG) and human complement (hC). In addition, post-TSA mice (n = 10) were administered equal dose of TSA at 8 h and 16 h after model induction. At 24 h after intracerebral injection, histological analysis was performed to assess the inhibitory effects of TSA on astrocyte damage, demyelination, and neuroinflammation in NMOSD mice, and western blotting was conducted to clarify the effect of TSA on the NF-κB and MAPK signaling pathways. Furthermore, flow cytometry and western blotting were conducted to verify the proapoptotic effects of TSA on neutrophils in vitro. RESULTS: There was a profound reduction in astrocyte damage and demyelination in the pre-TSA group and post-TSA group. However, prophylactic administration of TSA induced a better effect than therapeutic treatment. The number of infiltrated neutrophils was also decreased in the lesions of NMOSD mice that were pretreated with TSA. We confirmed that prophylactic administration of TSA significantly promoted neutrophil apoptosis in NMOSD lesions in vivo, and this proapoptotic effect was mediated by modulating the caspase pathway in the presence of inflammatory stimuli in vitro. In addition, TSA restricted activation of the NF-κB signaling pathway in vivo. CONCLUSION: Our data provide evidence that TSA can act as a prophylactic agent that reduces NMO-IgG-induced damage in the mouse brain by enhancing the resolution of inflammation by inducing neutrophil apoptosis, and TSA may serve as a promising therapeutic agent for neutrophil-associated inflammatory disorders, such as NMOSD.
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Abietanos/farmacologia , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Neuromielite Óptica/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Neutrófilos/efeitos dos fármacos , Abietanos/uso terapêutico , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Camundongos , Neuromielite Óptica/metabolismo , Neuromielite Óptica/patologia , Fármacos Neuroprotetores/uso terapêutico , Neutrófilos/metabolismo , Neutrófilos/patologiaRESUMO
The species Metidiocerus sp. belonging to the subfamily Idiocerinae (Hemiptera, Cicadellidae). Here, we sequenced and annotated the mitochondrial genome (mitogenome) of Metidiocerus sp. This mitogenome was 15,079 bp long and encoded 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and 2 ribosomal RNA unit genes (rRNAs), and one non-coding region. The nucleotide composition biases toward A and T, which together made up 77.4% of the entirety. All 13 PCGs were initiated by the ATN (ATG, ATT, ATA, and ATC) codon. All PCGs terminate with the stop codons TAA except for COX2, ND4, and ND1 ended with single T. A phylogenetic tree generated by the Bayesian method showed that Metidiocerus sp. is closely related to Idiocerus salicis and Idiocerus herrichii which enriched the mitochondrial genome data of Idiocerinae.
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In this study, we firstly reported the complete mitochondrial genome of Populicerus confuses. The complete mitochondrial genome was 16,395 bp in length which overall base composition was 41.43% A, 36.30% T, 11.54% C, and 10.73% G. It consisted of 13 protein-coding genes (PCGs), 22 tRNA genes, 2 rRNA genes (12S and 16S rRNA), and a control region (D-loop region). The complete mitochondrial genomes of P. confuses and other 9 species were used for phylogenetic analysis using the Bayesian method. The resulting phylogenetic tree confirms that the Populicerus populi is most closely related to P. confuses. The mitogenome provided the valuable evidence on phylogenetic relationship of the Idiocerinae at the molecular level.
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It has been revealed that gestational weight gain (GWG) influences the risk of autism spectrum disorder (ASD) in the offspring, but the findings are inconsistent. The current study aimed to evaluate the relationship between GWG and risk of ASD in offspring. Four electronic databases were searched up to August 28 2018 to identify observational studies reporting the association between GWG and risk of ASD in the offspring. Nine studies which met the inclusion criteria were included in the systematic review. Finally, five studies with a total of 3793 children with ASD were included in the meta-analysis. The-results indicated that excessive GWG might increase the risk of ASD in offspring (p = .0008, OR = 1.23, 95% confidence interval (CI) 1.09-1.38). More high quality cohort studies are needed to confirm this result. This research has the potential to inspire new research on ASD and promote efforts to design appropriate interventions against excessive GWG.Impact statementWhat is already known on this subject? It has been revealed that gestational weight gain (GWG) influences the risk of autism spectrum disorder (ASD) in the offspring, but the findings are inconsistent.What the results of this study add? This is the first systematic review and meta-analysis on the association between GWG and ASDs in offspring. This study suggested that excessive GWG was associated with higher risk of ASD in offspring.What the implications are of these findings for clinical practice and/or further research? More high quality cohort studies are needed to confirm this result. This research has the potential to inspire new research on ASD and promote efforts to design appropriate interventions against excessive GWG.
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Transtorno do Espectro Autista/epidemiologia , Ganho de Peso na Gestação/fisiologia , Índice de Massa Corporal , Criança , Feminino , Humanos , Gravidez , Fatores de RiscoRESUMO
Microcystis, the dominant species among cyanobacterial blooms, normally forms colonies under natural conditions but exists as single cells or paired cells in axenic laboratory cultures after long-term cultivation. Here, a bloom-forming Microcystis aeruginosa strain CHAOHU 1326 was studied because it presents a colonial morphology and grows on the water surface during axenic laboratory culturing. We first examined the morphological features of strain CHAOHU 1326 and three other unicellular M. aeruginosa strains FACHB-925, FACHB-940, and FACHB-975 cultured under the same conditions by scanning and transmission electron microscopy. Then, we compared the extracellular polysaccharide (EPS)-producing ability of colonial strain CHAOHU 1326 to that of the three unicellular M. aeruginosa strains, and found that strain CHAOHU 1326 produced a higher amount of EPS than the other strains during growth. Moreover, based on genome sequencing, multiple gene clusters implicated in EPS biosynthesis and a cluster of 12 genes predicted to be involved in gas vesicle synthesis in strain CHAOHU 1326 were detected. These predicted genes were all functional and expressed in M. aeruginosa CHAOHU 1326 as determined by reverse transcription PCR. These findings provide a physiological and genetic basis to better understand colony formation and buoyancy control during M. aeruginosa blooming.
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Microcystis/crescimento & desenvolvimento , Polissacarídeos Bacterianos/metabolismo , Vias Biossintéticas , Eutrofização , Genoma Bacteriano , Microcystis/genética , Microcystis/metabolismo , Microcystis/ultraestrutura , Filogenia , Polissacarídeos Bacterianos/genética , Microbiologia da ÁguaRESUMO
PURPOSE: To investigate the effect of early treatment of Class II division 1 malocclusion with T4K appliance on soft and hard tissue changes and prognosis of patients with mixed teeth. METHODS: Twenty patients with Class II malocclusion, 11 males and 9 females, aged from 9 to 14 years, with an average age of 11.05 years, were selected. All patients were treated with T4K appliance for 12 months. The changes of soft and hard tissues before, 12 months after and 36 months after orthodontic treatment were measured and compared, to explore the stability of T4K appliance in the treatment of Class â ¡ division 1 malocclusion. The data were analyzed with SPSS 25.0 software package. RESULTS: The hard tissue indexes U1-NA, U1-NA, L1-NB, L1-NB were significantly decreased (P<0.05) and U1-L1 was significantly increased (P<0.05). Soft tissue index UL-U1, LL-L1 increased significantly (P<0.05);overjet, overbite, E-upper-lip, E-lower-lip decreased significantly (P<0.05); nasolabial angle, sulcus dip, soft tissue thickness significantly increased (P<0.05). There was no significant difference between 12 months and 36 months after treatment (P>0.0.5). CONCLUSIONS: T4K appliance used for early treatment of Class â ¡ malocclusion can correct patients' poor oral habits, improve the relationship between oral and maxillofacial soft and hard tissues, with good long-term efficacy and stable curative effect.
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Má Oclusão Classe II de Angle , Sobremordida , Adolescente , Cefalometria , Criança , Feminino , Dureza , Humanos , Lábio , MasculinoRESUMO
AIMS: The aim of the present study was to assess how genetically increased Sarcoplasmic reticulum Ca2+-ATPase (Serca2a) expression affects cardiac injury after Ischemia/Reperfusion (I/R) exposure and the related mechanisms involved. METHODS AND RESULTS: Rats were subjected to Left Anterior Descending coronary artery (LAD) occlusion for 30 min followed by a 24-hour reperfusion. Cardiac function analysis revealed that cardiac function dramatically improved in Serca2a transgenic rats, (Serca2aTG) rats, compared to Wild Type (WT) rats. Serca2aTG rats developed a significantly smaller myocardial infarction size compared to those in WT group. The expression of the Bcl-2 was lower in Serca2aTG rats compared with WT rats; but, Bcl-2 expression was markedly increased in Serca2aTG rats compared with WT after I/R. In addition, Bax was markedly downregulated in Serca2aTG rats compared to WT group after I/R. Meanwhile, autophagy marker LC-3B was increased in Serca2aTG group, and p62 was only increased in WT group but not in Serca2aTG group in response to I/R. Electron microscope observation confirmed that there were more autophagosomes in Serca2aTG group than in WT rats after I/R. CONCLUSION: our findings demonstrated that the overexpression of Serca2a plays an important role in myocardial protection from I/R injury and postischemic functional recovery, which may be via antinecrotic, anti-apoptotic and pro-autophagy signal pathways. Our research provides solid basic data and new perspective on clinical treatment in heart failure patients with long-term over-expression of Serca2a.