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Thoracic aortic dissection (TAD) is a life-threatening vascular disease manifested as intramural bleeding in the medial layers of the thoracic aorta. The key histopathologic feature of TAD is medial degeneration, characterized by depletion of vascular smooth muscle cells (VSMCs) and degradation of extracellular matrix (ECM). MicroRNA, as essential epigenetic regulators, can inhibit the protein expression of target genes without modifying the sequences. This study aimed to elucidate the role and underlying mechanism of miR-20a, a member of the miR-17-92 cluster, in regulating ECM degradation during the pathogenesis of TAD. The expression of the miR-17-92 cluster was significantly increased in synthetic VSMCs derived from TAD lesions compared to contractile VSMCs isolated from normal thoracic aortas. Notably, the expression of miR-20a was increased in VSMCs in response to serum exposure and various stimuli. In TAD lesions, the expression of miR-20a was significantly negatively correlated with that of elastin. Elevated expression of miR-20a was also observed in thoracic aortas of TAD mice induced by ß-aminopropionitrile fumarate and angiotensin II. Overexpression of miR-20a via mimic transfection enhanced the growth and invasive capabilities of VSMCs, with no significant impact on their migratory activity or the expression of phenotypic markers (α-SMA, SM22, and OPN). Silencing of miR-20a with inhibitor transfection mitigated the hyperactivation of MMP2 in VSMCs stimulated by PDGF-bb, as evidenced by reduced levels of active-MMP2 and increased levels of pro-MMP2. Subsequently, TIMP2 was identified as a novel target gene of miR-20a. The role of miR-20a in promoting the activation of MMP2 was mediated by the suppression of TIMP2 expression in VSMCs. In addition, the elevated expression of miR-20a was found to be directly driven by Nanog in VSMCs. Collectively, these findings indicate that miR-20a plays a crucial role in maintaining the homeostasis of the thoracic aortic wall during TAD pathogenesis and may represent a potential therapeutic target for TAD.
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PURPOSE: This study aimed to show the outcomes of isolated tricuspid valve replacement (ITVR) after left-sided valve surgery (LSVS). METHODS: Patients who underwent ITVR after LSVS were divided into bioprosthetic tricuspid valve (BTV) and mechanical tricuspid valve (MTV) groups. Clinical data were collected and analyzed between groups. RESULTS: 101 patients were divided into BTV (n = 46) and MTV (n = 55) groups. The mean ages of the BTV and MTV groups were 63.4 ± 8.9 and 52.4 ± 7.6 years, respectively (P <0.01). There was no significant difference in 30-day mortality (BTV 10.9% vs. MTV 5.5%), early postoperative complications, and long-term tricuspid valve (TV)-related adverse events between these two groups. New-onset renal insufficiency was an independent risk factor for early mortality. Survival rates in the BTV group were 94.8% ± 3.6%, 86.5% ± 6.5%, and 54.2% ± 17.6% and in the MTV group were 96.0% ± 2.8%, 79.0% ± 7.4%, and 59.4% ± 14.8% at 1, 5, and 10 years, respectively (P = 0.826). CONCLUSION: The TV prosthesis selection in ITVR after LSVS seems to not affect 30-day mortality and early postoperative complications. Long-term survival and the occurrence of TV-related events were also comparable between these two groups.
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Bioprótesis , Procedimientos Quirúrgicos Cardíacos , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Insuficiencia de la Válvula Tricúspide , Humanos , Persona de Mediana Edad , Anciano , Válvula Tricúspide/diagnóstico por imagen , Válvula Tricúspide/cirugía , Resultado del Tratamiento , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Insuficiencia de la Válvula Tricúspide/diagnóstico por imagen , Insuficiencia de la Válvula Tricúspide/cirugía , Prótesis Valvulares Cardíacas/efectos adversos , Complicaciones Posoperatorias/etiología , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Estudios Retrospectivos , Bioprótesis/efectos adversosRESUMEN
Object: Knowledge about the risk factors of in-hospital mortality for acute type A aortic dissection (ATAAD) patients who received total arch procedure is limited. This study aims to investigate preoperative and intraoperative risk factors of in-hospital mortality of these patients. Methods: From May 2014 to June 2018, 372 ATAAD patients received the total arch procedure in our institution. These patients were divided into survival and death groups, and patients` in-hospital data were retrospectively collected. Receiver operating characteristic curve analysis was adopted to determine the optimal cut-off value of continuous variables. Univariate and multivariable logistic regression analyses were used to detect independent risk factors for in-hospital mortality. Results: A total of 321 patients were included in the survival group and 51 in the death group. Preoperative details showed that patients in the death group were older (55.4 ± 11.7 vs. 49.3 ± 12.6, P = 0.001), had more renal dysfunction (29.4% vs. 10.9%, P = 0.001) and coronary ostia dissection (29.4% vs. 12.2%, P = 0.001), and decreased left ventricular ejection fraction (LVEF) (57.5 ± 7.9% vs. 59.8 ± 7.3%, P = 0.032). Intraoperative results showed that more patients in the death group experienced concomitant coronary artery bypass grafting (35.3% vs. 15.3%, P = 0.001) with increased cardiopulmonary bypass (CPB) time (165.7 ± 39.0 vs. 149.4 ± 35.8â min, P = 0.003), cross-clamp time (98.4 ± 24.5 vs. 90.2 ± 26.9â min, P = 0.044), and red blood cell transfusion (913.7 ± 629.0 vs. 709.7 ± 686.6â ml, P = 0.047). Logistic regression analysis showed that age >55 years, renal dysfunction, CPB time >144â min, and RBC transfusion >1,300â ml were independent risk factors for in-hospital mortality in patients with ATAAD. Conclusion: In the present study, we identified that older age, preoperative renal dysfunction, long CPB time, and intraoperative massive transfusion were risk factors for in-hospital mortality in ATAAD patients with the total arch procedure.
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BACKGROUND: The study aimed to evaluate the prognostic value of preoperative systemic inflammation response index (SIRI) for acute type A aortic dissection (ATAD) following open surgery. METHODS AND RESULTS: Totally, 410 ATAD patients underwent open surgery from 2019 to 2021 were enrolled in the study. Among the patients, the in-hospital mortality was 14.4%. Cox regression (95%CI 1.033-1.114p < 0.001) and receiver operating characteristic curve analysis (AUC = 0.718, p < 0.001) demonstrated the prognostic role of SIRI for in-hospital mortality after surgery. The optimal cut-off value of SIRI for in-hospital mortality was identified as 9.43 by maximally selected Log-Rank statistics. The patients were divided into high SIRI group (SIRI ≥ 9.43) and low SIRI group (SIRI < 9.43)) after the linear inverse relationship between SIRI and hazard ratio for in-hospital mortality was demonstrated by restricted cubic spline analysis (p = 0.0742). The Kaplan-Meier analysis illustrated that in-hospital mortality increased significantly in high SIRI group (p < 0.001). In addition, elevating SIRI was significantly associated with the incidence of coronary sinus tear (95%CI 1.020-4.475p = 0.044). Furthermore, the incidence rate of postoperative complications including renal failure (p < 0.001) and infection (p = 0.019) was higher in high SIRI group. CONCLUSION: The study indicated that preoperative SIRI could provide strong prognostic value for in-hospital mortality in ATAD patients following open surgery. Thus, SIRI was a promising biomarker for risk stratification and management prior to open surgery.
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Disección Aórtica , Humanos , Pronóstico , Disección Aórtica/cirugía , Mortalidad Hospitalaria , Estimación de Kaplan-Meier , Inflamación , Estudios RetrospectivosRESUMEN
BACKGROUND: Aortic arch replacement(TAR) combined with frozen elephant trunk (FET) technique is a high-risk operation after previous cardiovascular surgery. The aim of the study was to review our strategy and outcomes in this cohort. METHOD: Data were reviewed for patients who underwent TAR combined with FET after previous cardiovascular surgery from January 2010 to December 2020. The patients were divided into elective group and non-selective group. RESULTS: 63 eligible patients were divided into elective(n = 44) and non-elective(n = 19) groups. The interval between two operations was shorter in non-elective group than elective groups (P = 0.001). The indication for reoperation was different in two groups (P = 0.000), however, the type of reoperations has no differences. Cardiopulmonary bypass time was shorter in elective group than non-elective group (P = 0.000). The over-all 30-day mortality rate was 17.5%, and it was higher in non-elective group (P = 0.013). The 24h drainage increased in non-elective group (P = 0.001) as well as re-explore rate for bleeding (P = 0.022). Postoperative hospital stay prolonged in non-elective group (P = 0.002). However, rates of survival without further aortic events were 72.3 ± 7.1% in elective group, 72.9 ± 13.5% in non-elective group at 5 years, respectively (P = 0. 955). CONCLUSION: Reduced 30-day mortality and shortened post-operative hospital stay was observed in elective group, however, long-term survival rate without reintervention were not affected.
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Disección Aórtica , Implantación de Prótesis Vascular , Humanos , Disección Aórtica/cirugía , Implantación de Prótesis Vascular/métodos , Prótesis Vascular , Reoperación , Aorta Torácica/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Background: As a key regulator of metabolic pathways, long non-coding RNA (lncRNA) has received much attention for its relationship with reprogrammed fatty acid metabolism (FAM). This study aimed to investigate the role of the FAM-related lncRNAs in the prognostic management of patients with lung adenocarcinoma (LUAD) using bioinformatics analysis techniques. Methods: We obtained LUAD-related transcriptomic data and clinical information from The Cancer Genome Atlas (TCGA) database. The lncRNA risk models associated with FMA were constructed by single-sample gene set enrichment analysis (ssGSEA), weighted gene co-expression network (WGCNA), differential expression analysis, overlap analysis, and Cox regression analysis. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves were utilized to assess the predictive validity of the risk model. Gene set variation analysis (GSVA) revealed molecular mechanisms associated with the risk model. ssGSEA and microenvironment cell populations-counter (MCP-counter) demonstrated the immune landscape of LUAD patients. The relationships between lncRNAs, miRNAs, and mRNAs were predicted by using LncBase v.2 and miRTarBase. The lncRNA-miRNA-mRNA regulatory network was visualized with Cytoscape v3.4.0. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed using DAVID v6.8. Quantitative real-time fluorescence PCR (qRT-PCR) was performed to verify the expression levels of the prognostic lncRNAs. Results: We identified 249 differentially expressed FMA-related lncRNAs in TCGA-LUAD, six of which were used to construct a risk model with appreciable predictive power. GSVA results suggested that the risk model may be involved in regulating fatty acid synthesis/metabolism, gene repair, and immune/inflammatory responses in the LUAD process. Immune landscape analysis demonstrated a lower abundance of immune cells in the high-risk group of patients associated with poor prognosis. Moreover, we predicted 279 competing endogenous RNA (ceRNA) mechanisms for 6 prognostic lncRNAs with 39 miRNAs and 201 mRNAs. Functional enrichment analysis indicated that the ceRNA network may be involved in the process of LUAD by participating in genomic transcription, influencing the cell cycle, and regulating tissue and organogenesis. In vitro experiments showed that prognostic lncRNA CTA-384D8.35, lncRNA RP5-1059L7.1, and lncRNA Z83851.4 were significantly upregulated in LUAD primary tumor tissues, while lncRNA RP11-401P9.4, lncRNA CTA-384D8.35, and lncRNA RP11-259K15.2 were expressed at higher levels in paraneoplastic tissues. Conclusion: In summary, the prognostic factors identified in this study can be used as potential biomarkers for clinical applications. ceRNA network construction provides a new vision for the study of LUAD pathogenesis.
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BACKGROUND: Diabetic cardiomyopathy (DCM) results from pathological changes in cardiac structure and function caused by diabetes. Excessive oxidative stress is an important feature of DCM pathogenesis. MicroRNAs (miRNAs) are key regulators of oxidative stress in the cardiovascular system. In the present study, we screened for the expression of oxidative stress-responsive miRNAs in the development of DCM. Furthermore, we aimed to explore the mechanism and therapeutic potential of miR-92a-2-5p in preventing diabetes-induced myocardial damage. METHODS: An experimental type 2 diabetic (T2DM) rat model was induced using a high-fat diet and low-dose streptozotocin (30 mg/kg). Oxidative stress injury in cardiomyocytes was induced by high glucose (33 mmol/L). Oxidative stress-responsive miRNAs were screened by quantitative real-time PCR. Intervention with miR-92a-2-5p was accomplished by tail vein injection of agomiR in vivo or adenovirus transfection in vitro. RESULTS: The expression of miR-92a-2-5p in the heart tissues was significantly decreased in the T2DM group. Decreased miR-92a-2-5p expression was also detected in high glucose-stimulated cardiomyocytes. Overexpression of miR-92a-2-5p attenuated cardiomyocyte oxidative stress injury, as demonstrated by increased glutathione level, and reduced reactive oxygen species accumulation, malondialdehyde and apoptosis levels. MAPK interacting serine/threonine kinase 2 (MKNK2) was verified as a novel target of miR-92a-2-5p. Overexpression of miR-92a-2-5p in cardiomyocytes significantly inhibited MKNK2 expression, leading to decreased phosphorylation of p38-MAPK signaling, which, in turn, ameliorated cardiomyocyte oxidative stress injury. Additionally, diabetes-induced myocardial damage was significantly alleviated by the injection of miR-92a-2-5p agomiR, which manifested as a significant improvement in myocardial remodeling and function. CONCLUSIONS: miR-92a-2-5p plays an important role in cardiac oxidative stress, and may serve as a therapeutic target in DCM.
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Diabetes Mellitus Tipo 2 , Cardiomiopatías Diabéticas , MicroARNs , Animales , Apoptosis , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Cardiomiopatías Diabéticas/genética , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/patología , Glucosa/metabolismo , Glutatión/metabolismo , Malondialdehído/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Miocitos Cardíacos/metabolismo , Estrés Oxidativo , Proteínas Serina-Treonina Quinasas , Ratas , Especies Reactivas de Oxígeno/metabolismo , Serina/metabolismo , Estreptozocina/metabolismoRESUMEN
BACKGROUND: After proximal aortic surgery, total arch replacement (TAR) may again be needed because of recurrent dissection or aneurysm. This paper analyzed the relevant data of this technology with hopes of improving cognition and treatment. METHODS: There were a total of 60 eligible cases of secondary TAR after proximal aortic surgery in our center from 2010 to 2020. The primary surgical procedures included aortic valve replacement (AVR), ascending aortic replacement, Bentall, hemi-arch replacement, and thoracic endovascular aortic repair (TEVAR). The data were analyzed using the IBM SPSS Statistics 23.0 for Windows™ and presented as the mean ± standard deviations and direct frequencies, as appropriate. RESULTS: The interval between two operations was 44.8±53.6 months, 24 cases (40%) underwent emergency operation, the recurrence of type A dissection included 51 cases, accounting for 85% of the causes of total arch re-replacement. In the second surgical procedures, the ascending + TAR + stented elephant trunk (SET) implantation accounted for 75.0%. The overall surgical success rate was 98.3%. Postoperative respiratory complications were the most common, including infection, pneumothorax and hemothorax in 21 cases (35.6%). The second most common complication was acute kidney injury (AKI) in six cases (10.2%), and neurological complications took place in three cases (5.1%). The 30-day mortality rate was 15.3% and the 1-, 3- and 5-year survival rates were 96.0%, 84.0%, and 76.0%, respectively. CONCLUSIONS: The recurrence of dissection is the main cause of TAR after proximal aortic surgery, followed by aneurysm and the resurgical criteria for aneurysm needs to be unified. In addition to TAR, SET also is widely used. Despite high early mortality, its long-term prognosis is acceptable.
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Aneurisma de la Aorta Torácica , Disección Aórtica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Disección Aórtica/complicaciones , Disección Aórtica/diagnóstico , Disección Aórtica/cirugía , Aorta/cirugía , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/complicaciones , Aneurisma de la Aorta Torácica/diagnóstico , Aneurisma de la Aorta Torácica/cirugía , Implantación de Prótesis Vascular/métodos , Humanos , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Stents/efectos adversos , Resultado del TratamientoRESUMEN
Objective: Though the prognostic value of the model for end-stage liver disease (MELD) score in tricuspid surgery was confirmed, the unstable international normalized ratio (INR) may affect the evaluation effectiveness of the MELD score for isolated tricuspid valve replacement (ITVR). The aim of the study was to assess the prognostic value of modified MELD for ITVR. Methods and Results: A total of 152 patients who underwent ITVR were evaluated. The adverse outcome was defined as in-hospital mortality after surgery. The receiver operating characteristic (ROC) curve analysis demonstrated that a modified MELD score with albumin replacing INR (MELD-albumin) score presented well prognostic value [area under the curve (AUC) = 0.731, p = 0.006] for in-hospital mortality. Through Cox regression and further interval validation, the MELD-albumin score was identified as an independent predictor for in-hospital mortality. The optimal cutoff value of MELD-albumin was identified as 8.58 through maximally selected log-rank statistics. In addition, restricted cubic spline analysis demonstrated the linear inverse relationship between MELD-albumin and hazard ratio (HR) for in-hospital mortality. Kaplan-Meier analysis illustrated that in-hospital mortality was increased significantly in the high MELD-albumin (MELD-albumin ≥8.58) group than in the low MELD-albumin group (MELD-albumin <8.58; p < 0.001). Furthermore, high MELD-albumin was associated with lower body mass index (BMI), the incidence of lower extremities edema and moderate drinking history, and the MELD-albumin score was correlated with the value of aspartate transaminase (AST), alanine transaminase (ALT), and albumin. Furthermore, the incidence of renal failure (p = 0.003) and pulmonary infection (p = 0.042) was increased significantly in the high MELD-albumin group. Conclusion: The MELD-albumin score could provide prognostic value for ITVR. In addition, the MELD-albumin score was useful in risk stratification and patient selection for patients with tricuspid regurgitation (TR) prior to ITVR.
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Decellularization is a promising technique to produce natural scaffolds for tissue engineering applications. However, non-crosslinked natural scaffolds disfavor application in cardiovascular surgery due to poor biomechanics and rapid degradation. Herein, we proposed a green strategy to crosslink and functionalize acellular scaffolds via the self-assembly of copper@tea polyphenol nanoparticles (Cu@TP NPs), and the resultant nanocomposite acellular scaffolds were named as Cu@TP-dBPs. The crosslinking degree, biomechanics, denaturation temperature and resistance to enzymatic degradation of Cu@TP-dBPs were comparable to those of glutaraldehyde crosslinked decellularized bovine pericardias (Glut-dBPs). Furthermore, Cu@TP-dBPs were biocompatible and had abilities to inhibit bacterial growth and promote the formation of capillary-like networks. Subcutaneous implantation models demonstrated that Cu@TP-dBPs were free of calcification and allowed for host cell infiltration at Day 21. Cardiac patch graft models confirmed that Cu@TP-dBP patches showed improved ingrowth of functional blood vessels and remodeling of extracellular matrix at Day 60. These results suggested that Cu@TP-dBPs not only had comparable biomechanics and biostability to Glut-dBPs, but also had several advantages over Glut-dBPs in terms of anticalcification, remodeling and integration capabilities. Particularly, they were functional patches possessing antibacterial and proangiogenic activities. These material properties and biological functions made Cu@TP-dBPs a promising functional acellular patch for cardiovascular applications.
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PURPOSE: In this study, we compared the early results between the extensive arch repair with a novel two-branched stent graft (TSG) and the traditional technique. METHODS: Between 2013 July and 2015 March, 63 acute type A aortic dissection (ATAAD) patients from four cardiac centers with indications for extensive arch repair were included in this study. Finally, 28 patients were involved in the traditional procedure (TP) group (23 males with the age of 49.75 ± 9.26 years) and 35 patients were involved in the TSG group (29 males with the age of 53.82 ± 8.17 years). RESULTS: The operation was successful in all patients. The selective cerebral perfusion time, total operation time, and chest drainage within 24 hours after the operation in the TSG group were significantly less than those in the TP group (P ≤0.05). The mean follow-up time was 11.17 ± 1.74 months in the TP group and 11.94 ± 4.29 months in the TSG group. No statistical differences were found in aortic diameter, false lumen diameter, and true lumen diameter at the diaphragmatic level during the follow-up. CONCLUSION: Our technique with a novel TSG simplified the extensive arch repair procedure and was an effective way for the treatment of ATAAD.
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Aneurisma de la Aorta Torácica , Disección Aórtica , Implantación de Prótesis Vascular , Adulto , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Prótesis Vascular , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/métodos , Humanos , Masculino , Persona de Mediana Edad , Stents , Resultado del TratamientoRESUMEN
OBJECTIVE: Systemic immune-inflammation index (SII) is a biomarker that reflect systemic inflammation. We aimed to assess the value of SII in prediction of short-term outcomes in acute type A aortic dissection (ATAD) patients undergoing surgery. METHOD: All patients underwent surgery for ATAD at our institution from 2018 to 2020 (n = 324) were retrospectively reviewed and divided into low SII (<1582.6 × 109 /L) and high SII (≥1582.6 × 109 /L) group according to optimal cut-off values defined by receiver operating characteristic curve. Cox regression and Kaplan-Meier analyses were performed to illustrate the correlation between SII and postoperative short-outcomes, including 30-day mortality and main complications after surgery. RESULTS: In total, 48 (14.8%) patients died in 30 days after ATAD surgery. And multivariable Cox analysis demonstrated that high preoperative SII was closely related with 30-day mortality (hazard ratio: 3.532, 95% confidence interval: 1.719-7.255, p = .001). Furthermore, Kaplan-Meier analysis illustrated that the short-term mortality rate increased significantly in high SII group (p < .001). In addition, the incidence of main postoperative complications including major adverse cardiovascular events (p = .001) and multiorgan failure (p = .002) were higher in high SII group. However, the length of intensive unit stay (p = .909) and hospital stay (p = .836) presented no difference in two groups. CONCLUSION: The study indicated that SII was an available biomarker to predict postoperative short-term prognosis, but not length of stay in intensive care unit and hospital in ATAD patients. And SII may be applied to risk stratification and patient selection in ATAD patients before surgery.
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Disección Aórtica , Inflamación , Disección Aórtica/cirugía , Humanos , Estimación de Kaplan-Meier , Pronóstico , Estudios RetrospectivosRESUMEN
An efficient and simple method to obtain aortic media for primary culture of rat vascular smooth muscle cells (RVSMCs) is developed. The main steps to obtain aortic media include isolation of rat aortic artery, removal of the fat tissue and branches, separation of longitudinal cutting edge, and peeling off the adventitia. Then, aortic media was used to obtain RVSMCs by our tissue explants method and the enzyme digestion method. The removal efficiency of the intima and adventitia was confirmed by hematoxylin-eosin and immunohistochemical staining. Morphology and immunofluorescent staining were used to identify cells and cell purity. RVSMCs at the 3rd and 8th passages were isolated by our tissue explants method; the enzyme digestion method and the traditional tissue explants method were compared respectively. Western blotting and gel contraction assay were used to investigate the phenotype and contraction ability of RVSMCs obtained by the different methods. Compared with the other methods, RVSMCs isolated by our method showed higher purity and demonstrated "contractile" phenotype with retained contraction ability for more passages. And the aortic media obtained showed no visible damage with few endothelial cells and fibroblasts remained. An efficient and simple method was established to obtain rat aortic media for primary culture of RVSMCs with high purity, "contractile" phenotype characteristics, and more stable during subculturing.
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Aorta/citología , Separación Celular/métodos , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/citología , Animales , Células Cultivadas , Fenotipo , Ratas Sprague-DawleyRESUMEN
Di-2-ethylhexyl phthalate (DEHP) is a type of plasticizer widely used in industry. It is well-known for its toxic effects to endocrine and reproductive systems and has been detected in amniotic fluid and placenta. In the present study, we explored the effects of DEHP on heart development by using zebrafish as a model organism. DEHP (0.02 pg) was injected into the yolk sac of zebrafish embryos at the one-cell stage. No significant difference was found in embryonic lethality between control and DEHP groups at 1-day postfertilization (dpf), but mortality significantly increased in DEHP groups at 2 and 3 dpf. The average heart rate was significantly reduced in the surviving DEHP-treated zebrafish larvae at 3 and 4 dpf. In addition, massive pericardial edema was found in DEHP-treated zebrafish (12.6 ± 1.5%), which was significantly higher than that of the control group. Serious heart looping disorder was also observed in DEHP-treated larvae, mainly manifested with an elongated atrial-ventricular distance. Moreover, the expression of heart development transcription factors was affected by DEHP injection. Real-time polymerase chain reaction confirmed that five transcription factors (hand2, tp53, mef2c, esr1, and tbx18) were significantly downregulated in the DEHP group at 2 dpf, and three transcription factors (zic3, tcf21, and gata4) were significantly upregulated. Our results emphasize the need for the development of a nontoxic plasticizer to prevent possible deleterious effects on humans and other life-forms.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/efectos de los fármacos , Dietilhexil Ftalato/toxicidad , Embrión no Mamífero/efectos de los fármacos , Corazón/efectos de los fármacos , Corazón/crecimiento & desarrollo , Glicoproteínas de Membrana/efectos de los fármacos , Proteínas de Pez Cebra/efectos de los fármacos , Pez Cebra/crecimiento & desarrollo , Animales , Desarrollo Embrionario/efectos de los fármacos , Humanos , Exposición Profesional/efectos adversos , Organogénesis/efectos de los fármacos , Plastificantes/toxicidad , Contaminantes Químicos del Agua/toxicidadRESUMEN
Finding the best applications of graphene, and the continuous and scalable preparation of graphene with high quality and high purity, are still two major challenges. Herein, a "pulse-etched" microwave-induced "snowing" (PEMIS) process is developed for continuous and scalable preparation of high-quality and high-purity graphene directly in the gas phase, which is found to have excellent thermotherapeutic effects. The obtained graphene exhibits small size (≈180 nm), high quality, low oxygen content, and high purity, together with a high gas-solid conversion efficiency of ≈10.46%. Considering the intrinsic characteristics of this high-purity and small-sized biocompatible graphene, in particular the low-frequency microwave absorption property as well as the good thermal transformation ability, a graphene-based combination therapeutic system is demonstrated for microwave thermal therapy (MTT) for the first time, exhibiting a high tumor ablation rate of ≈86.7%. This is different from the principle of ions vibrating in a confined space used by current MTT sensitization materials. Not limited to this application, it is foreseen that this PEMIS-based high-quality graphene will allow the search for further suitable applications of graphene.
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Developing a simple and industrially scalable method to produce graphene with high quality and low cost will determine graphene's future. The two conventional approaches, chemical vapor deposition and liquid-phase exfoliation, require either costly substrates with limited production rate or complicated post treatment with limited quality, astricting their development. Herein, an extremely simple process is presented for synthesizing high quality graphene at low-cost in the gas phase, similar to "snowing," which is catalyst-free, substrate-free, and scalable. This is achieved by utilizing corona discharge of SiO2 /Si in an ordinary household microwave oven at ambient pressure. High quality graphene flakes can "snow" on any substrate, with thin-flakes even down to the monolayer. In particular, a high yield of ≈6.28% or a rate of up to ≈0.11 g h-1 can be achieved in a conventional microwave oven. It is demonstrated that the snowing process produces foam-like, fluffy, 3D macroscopic architectures, which are further used in strain sensors for achieving high sensitivity (average gauge factor ≈ 171.06) and large workable strain range (0%-110%) simultaneously. It is foreseen that this facile and scalable strategy can be extended for "snowing" other functional 2D materials, benefiting their low-cost production and wide applications.
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BACKGROUND: Esophageal cancer (EC) remains one of the major causes of cancer incidence and mortality worldwide. Genetic factors, such as single nucleotide polymorphisms (SNPs), may contribute to the carcinogenesis of EC. METHODS: We conducted a hospital based case-control study to evaluate the genetic susceptibility of SNPs on the development of EC. A total of 629 esophageal squamous cell carcinoma (ESCC) cases and 686 controls were enrolled for this study. Seven PADI4 SNPs were determined by ligation detection reaction method. RESULTS: Our findings suggested that the PADI4 rs2240337 GA/AA variants were significantly associated with decreased risk of ESCC. Haplotype PADI4 Ars2477137Crs1886302Grs11203366Grs16825533Grs2240337Ars1635564Ars1635562 and Crs2477137Trs1886302Grs11203366Ars1635564Grs2240337Crs1635564Trs1635562 polymorphism was correlated with decreased susceptibility to ESCC, while Crs2477137Trs1886302Ars11203366Ars1635564Grs2240337Ars1635564Ars1635562 was correlated with increased susceptibility of ESCC. Stratification analyses demonstrated that smoking significantly increased ESCC risk in PADI4 rs11203366 AG/AA, rs1886302 CC/CT, rs1635562 AT, rs1635564 CA and rs2477137 AC genotype. Alcohol drinking increased ESCC risk in PADI4 rs11203366 AG, rs1635562 AT, rs1635564 CA, rs2477137 AC, rs1886302 CT genotype. In younger cohort (<63 years), rs11203366 AA genotype was associated with increased risk of ESCC. PADI4 rs1886302 CC variant was associated with ESCC susceptibility in female cohort. CONCLUSIONS: Our study suggested that PADI4 rs2240337 G>A polymorphism may be correlated with individual susceptibility to ESCC. PADI4 rs11203366, rs1886302, rs1635562, rs1635564 and rs2477137 polymorphisms were implicated with altered susceptibility of ESCC based on sex, age, smoking status and alcohol consumption. However, larger studies among different ethnic populations and further experiments using genetically mutated cells or animals are warranted to verify our conclusion.
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Vitamin D receptor (VDR) gene polymorphisms have been reported to increase susceptibility to some malignant tumors, yet the effect on gastric cardiac adenocarcinoma susceptibility remains unknown. Here, we conducted a hospital-based case-control study to examine the correlation of single nucleotide polymorphisms of VDR rs2107301T>C, rs2228570C>T, rs1989969C>T and rs11568820 G>A and gastric cardiac adenocarcinoma susceptibility. A total 330 cases and 608 controls were enrolled in the study. Using ligation detection reaction, we found that the variant alleles of the four polymorphisms were not associated with risk of gastric cardiac adenocarcinoma. Further stratified analyses showed that there was an increased risk associated with VDR rs1989969 polymorphism among patients who were drinking or aged <60. The haplotypes VDR Trs2107301Trs2228570Crs1989969Grs11568820 reduced the susceptibility. This study demonstrated that VDR rs1989969 polymorphism was involved in the carcinogenesis of gastric cardiac adenocarcinoma, especially increased the risk in the younger and alcohol drinking Chinese population.
Asunto(s)
Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Receptores de Calcitriol/genética , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/genética , Adulto , Anciano , Alelos , Estudios de Casos y Controles , Femenino , Ligamiento Genético , Genotipo , Humanos , Desequilibrio de Ligamiento/genética , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Vigilancia de la Población , RiesgoRESUMEN
BACKGROUND: Esophageal cancer (EC) is the sixth leading cause of cancer-associated death worldwide. The interaction of environmental risk factors and genetic factors might contribute to the carcinogenesis of EC synergistically. RESULTS: All seven single locus polymorphisms of ALDH3B2 were not associated with risk of ESCC as evaluated by allelic, dominant, co-dominant, recessive and Cochran-Armitage trend tests. Stratified analyses showed these SNPs were not correlated with the susceptibility of ESCC according to different age, gender, cigarette smoking and alcohol drinking status. None of the major haplotypes were related with ESCC susceptibility. MATERIALS AND METHODS: We conducted a hospital-based case-control study to evaluate the combined effects of environmental risk factors and the single nucleotide polymorphisms (SNPs) of ALDH3B2 gene on the development of esophageal squamous carcinoma (ESCC). A total of 1043 ESCC cases and 1315 controls were recruited for this study. Seven ALDH3B2 SNPs and four environmental factors were selected as independent variables. ALDH3B2 SNPs were determined by ligation detection reaction method. CONCLUSIONS: Our study suggested that ALDH3B2 rs34589365, rs3741172, rs4646823, rs78402723, rs7947978, rs866907 and rs9787887 polymorphisms were not implicated with altered susceptibility of ESCC according to different age, gender, cigarette smoking and alcohol drinking status. Yet this conclusion needs to be verified in larger studies among different ethnic populations with validation design, the biological function of these SNPs in carcinogenesis are subject to further investigation.