[Overexpression of connexin 40 (Cx40) inhibits the proliferation of H9c2 cardiomyocytes in rats by cell cycle arrest].

Objective To establish a stable strain of H9c2 cardiomyocytes overexpressing Cx40 and preliminarily investigate the effect of lentiviral vector-mediated Cx40 protein overexpression on the proliferation of H9c2 cells and its related mechanisms. Methods The Cx40 gene fragment was cloned from H9c2 cells by PCR and linked with lentivirus vector pLVX-IRES-Puro to obtain the recombinant plasmid pLVX-Flag-Cx40. Recombinant lentiviral particles carrying Flag-Cx40 were obtained by cotransfection with packaging plasmids into HEK293T cells. A stable expression strain (H9c2-Flag-Cx40 cell) was screened from infected H9c2 cells by purinomycin. The expression of Cx40 protein was detected by Western blot analysis, and the effect of Cx40 on H9c2 cells proliferation was determined by CCK-8 assay; cell cycle changes were measured by flow cytometry; the expression of the cell cycle protein cyclin D1 was detected by qRT-PCR and Western blot analysis. Co-immunoprecipitation (Co-IP) immunoprecipitation and Western blot analysis were used to identify the binding of Cx40 and Yes associated protein (YAP) in H9c2 cells; cytoplasmic and cytosolic proteins were isolated to detect the effect of Cx40 on the localization of YAP using Western blot analysis. Results Sequencing results showed that the recombinant pLVX-Flag-Cx40 expression vector was successfully established. A stable transfected cell line containing recombinant Flag-Cx40 lentivirus (H9c2-Flag-Cx40 cell) was successfully constructed from H9c2 cells. Compared with the control group, overexpression of Cx40 significantly reduced the proliferation of H9c2 cells, arrested the cell cycle at G0/G1 and reduced cyclin D1 expression. A significant increase in YAP expression was observed in the cytoplasm of the H9c2-Flag-Cx40 stable cell line, while the expression in the nucleus was significantly reduced. Cx40 bound to YAP in the cytoplasm and prevented it from entering the nucleus to play the role of transcriptional coactivation. Conclusion Overexpression of Cx40 induces cell-cycle arrest at G0/G1 phase and inhibits the proliferation in H9c2 cells.

[Application of radial artery in total arterial coronary revascularization in elderly patients].

OBJECTIVE: To summarize the application experience and clinical effect of radial artery in total arterial coronary revascularization (TAR) in elderly patients. METHODS: Retrospectively analyzed the clinical data of patients who underwent TAR at the University of Hong Kong Shenzhen Hospital from July 1, 2020 to May 30, 2022. Patients were divided into ≥ 65-year-old group and < 65-year-old group according to age. The radial artery blood flow, diameter, intimal integrity and Allen test were evaluated by ultrasound before operation. The distal ends of radial artery were collected for pathological examination during operation. Coronary artery CT angiography (CTA) was examined postoperatively and follow up. The safety and reliability of ultrasonic assessment of radial artery and application of radial artery in elderly patients with TAR were summarized and analyzed. RESULTS: A total of 101 patients received TAR, including 35 cases aged ≥ 65 years old, 66 cases aged < 65 years old; 78 cases used bilateral radial arteries, and 23 cases used unilateral radial arteries. 4 cases of bilateral internal mammary arteries. All the proximal ends of the radial artery were anastomosed to the proximal end of the ascending aorta, 34 cases were performed of "Y" grafts, and 4 cases were sequential anastomoses. There was no in-hospital death and perioperative cardiovascular events. Perioperative cerebral infarction occurred in 3 patients. 1 patients was reoperated for bleeding. Intra-aortic balloon pump (IABP) assistance was used in 21 patients. Poor wound healing occurred in 2 cases and healed well after debridement. Follow-up of 2 to 20 months after discharge showed no internal mammary artery occlusion and 4 radial artery occlusions; no major adverse cardiovascular and cerebrovascular event (MACCE) occurred, and the survival rate was 100%. There was no significant difference in the above perioperative complications and follow-up endpoints between the two age groups. CONCLUSIONS: By adjusting the order of bypass anastomosis and optimizing the preoperative evaluation method, radial artery combined with internal mammary artery can obtain better outcome early in TAR, and can be safely and reliably applied to elderly patients.

Efficacy of endovascular repair in the treatment of retrograde ascending aortic intramural haematoma.

BACKGROUND: The current treatment for retrograde ascending aortic intramural hematoma (RAIMH) remains challenging. This study aims to summarize the short-term results of endovascular repair in the treatment of retrograde ascending aortic intramural hematoma. METHODS: Between June 2019 and June 2021, 21 patients (16 males and 5 females) with a retrograde ascending aortic intramural hematoma, aged 53 ± 14years, received an endovascular repair in our hospital. All cases involved an ascending aortic or aortic arch intramural hematoma. 15 patients had an ulcer on the descending aorta combined with an intramural hematoma in the ascending aorta and 6 patients had typical dissection changes on the descending aorta combined with an intramural hematoma in the ascending aorta. All patients had a successful endovascular stent-graft repair, with 10 cases operated on in the acute phase (<14 days) and 11 cases in the chronic phase (14-35 days). RESULTS: A single-branched aortic stent graft system was implanted in 10 cases, a straight stent in 2 cases, and a fenestrated stent in 9 cases. All surgeries were technically successful. One of the patients developed a new rupture 2 weeks after surgery and was converted to a total arch replacement. No perioperative stroke, paraplegia, stent fracture or displacement, limb or abdominal organ ischemia occurred. The intramural hematomas started being absorbed on CT angiography images before discharge. There was no incidence of postoperative 30-day mortality, and the intramural hematomas in the ascending aorta and aortic arch were fully or partly absorbed. CONCLUSION: Endovascular repair of retrograde ascending aortic intramural hematoma was shown to be safe and effective, and correlated with favorable short-term results.

Thoracic Endovascular Repair for Aortic Arch Pathologies with Surgeon Modified Fenestrated Stent Grafts: A Multicentre Retrospective Study.

OBJECTIVE: To evaluate the outcome of thoracic endovascular repair (TEVAR) for aortic arch pathologies with surgeon modified fenestrated stent grafts. METHODS: A multicentre, retrospective study consisting of consecutive patients from seven centres treated with surgeon modified fenestrated stent grafts for aortic arch pathologies was conducted. A technique to align fenestrations and supra-aortic vessels was applied. Rates of technical success, mortality, complications, and re-interventions were evaluated. RESULTS: Between February 2016 and January 2020, 513 consecutive patients with aortic arch pathologies received TEVAR with surgeon modified fenestrated stent grafts. The technical success rate was 98.6% (n = 506). In total, 626 fenestrations were created to revascularise 684 branch arteries of the aortic arch. There were 13 deaths and 15 re-interventions within 30 days of the operation. The estimated clinical success rate at 30 days was 94.4% (95% confidence interval [CI] 92.4 - 96.4), the estimated survival at 30 days was 97.5% (95% CI 96.1 - 98.9), and the estimated freedom from re-intervention at 30 days was 97.1% (95% CI 95.7 - 98.5). The median follow up was 27 (interquartile range 13 - 31) months. During follow up, there were five aortic related deaths, three non-aortic related deaths, and four deaths of unknown cause. Eighteen patients underwent re-intervention. The estimated clinical success rate at 24 months was 88.2% (95% CI 85.5 - 91.0), the estimated survival at 24 months was 94.9% (95% CI 92.7 - 97.1), and the estimated freedom from re-intervention at 24 months was 93.1% (95% CI 91.0 - 95.3). In total, 18 cases of stroke were recorded, including 12 within 30 days and six during follow up; six cases of retrograde type A aortic dissection were recorded, including five within 30 days and one during the follow up. CONCLUSION: TEVAR with surgeon modified fenestrated stent grafts for the treatment of aortic arch pathologies provides acceptable outcomes. Further follow up is required to confirm the benefits of this approach.

Exploration of Simplified Intraluminal TEVAR Technique for the Treatment of Aortic Arch Disease.

OBJECTIVE: The positional relationship between the three branches of the aortic arch was determined in normal people. This study provides data to support the customization of aortic arch stents and simplifies intraluminal treatment. METHODS: From January 2019 to August 2019, 120 patients who met the inclusion criteria were examined by CT angiography. The ratio of the distance from the midpoint of the three-branch opening onto the anterior wall to the cross-sectional diameter of the aortic arch was calculated. The positional relationship among the three-branch openings was obtained and the data were analyzed statistically. RESULTS: The three-branch openings were not in a straight line. The positional relationship among the three-branch openings was divided into four types, which were not statistically different between sex and age (P>0.05). CONCLUSION: By measuring the opening position of the three aortic branches, the positional relationship among the three branches was defined to provide a theoretical basis for the design of intraluminal stents and simplified intracavity thoracic endovascular aortic repair (TEVAR) technology.

Exploration of Simplified Intraluminal TEVAR Technique for the Treatment of Aortic Arch Disease

Abstract Objective: The positional relationship between the three branches of the aortic arch was determined in normal people. This study provides data to support the customization of aortic arch stents and simplifies intraluminal treatment. Methods: From January 2019 to August 2019, 120 patients who met the inclusion criteria were examined by CT angiography. The ratio of the distance from the midpoint of the three-branch opening onto the anterior wall to the cross-sectional diameter of the aortic arch was calculated. The positional relationship among the three-branch openings was obtained and the data were analyzed statistically. Results: The three-branch openings were not in a straight line. The positional relationship among the three-branch openings was divided into four types, which were not statistically different between sex and age (P>0.05). Conclusion: By measuring the opening position of the three aortic branches, the positional relationship among the three branches was defined to provide a theoretical basis for the design of intraluminal stents and simplified intracavity thoracic endovascular aortic repair (TEVAR) technology.

Research on clinical characteristics and prognostic analysis of heparin-induced thrombocytopenia after surgery for acute type a aortic dissection.

PURPOSE: The present study aimed to explore the clinical characteristics of heparin-induced thrombocytopenia (HIT) after surgery for acute type A aortic dissection and perform a relevant prognostic analysis. METHODS: After continuous observation and analysis of 204 patients who underwent acute type A aortic dissection, we found that blood platelets decreased significantly after surgery and that these patients can be suspected to suffer HIT based on relevant 4Ts scores. For these suspected HIT patients, a latex particle-enhanced immunoturbidimetric assay was conducted to detect heparin-induced antibodies. Perioperative clinical data of patients in HIT and non-HIT groups were recorded as were blood platelet counts, HIT antibody test results, 4Ts scores, thromboembolic complications, clinical prognosis and outcomes. RESULTS: In the present study, 38 suspected HIT patients, 16 HIT patients and 188 non-HIT patients were selected in the clinical setting. Among them, HIT patients were found to have prolonged cardiopulmonary bypass time (223 min on average vs. 164 min) and delayed aortic cross-clamp time (128 min on average vs. 107 min), and these differences between HIT patients and non-HIT patients were significant (P < 0.05). Additionally, the HIT group required longer operation time and higher dose of heparin, but showing no statistical differences (P > 0.05). The transfusions of blood platelets in the HIT group and non-HIT group were 18.7 ± 5.0u and 15.6 ± 7.34 u, respectively. In the HIT group, the mechanic ventilation time and the length of ICU stay were longer comparing the non-HIT group(P < 0.05), though no significant differences in total length of stay or In-hospital mortality were observed (P > 0.05). The incidence of continuous renal replacement therapy in HIT group was higher than the non-HIT group (P < 0.05). Additionally,there were no significant differences in 24-h postoperative drainage or reoperation for bleeding in both group(P > 0.05). However, the HIT antibody titer in the HIT group was significantly higher than that in the Suspected HIT group (2.7 ± 0.8 U/mL vs. 0.3 ± 0.2 U/mL) (P < 0.05). Among patients diagnosed with HIT, the incidence of thromboembolism reached 31.5%.For example, two HIT patients newly developed thromboembolism in both lower extremities,and three patients experienced cerebral infarction. CONCLUSIONS: After surgery for acute type A aortic dissection, HIT patients developed postoperative complications, the duration of ventilatory support and length of ICU stay were extended, and the incidence of thromboembolism increased. HIT antibody detection and risk classification should be implemented for high-risk patients showing early clinical characteristics.

Changes in Coagulation and Fibrinolysis Systems During the Perioperative Period of Acute Type A Aortic Dissection.

BACKGROUND: Acute type A aortic dissection (ATAAD) has a high risk of perioperative bleeding and often requires extensive blood product infusions. Analysis of the changes in coagulation and fibrinolysis is both helpful for proper treatment and an improved prognosis. The present study investigated the changes in the coagulation and fibrinolysis systems during the perioperative period of ATAAD. METHODS: Twenty-two patients with ATAAD were included in this study. After diagnosis, all patients underwent ascending aorta replacement, aortic arch replacement, and implantation of a special stented endovascular graft. The control group included 25 patients undergoing elective aortic surgery. Baseline preoperative, intraoperative, and postoperative data were collected in both groups. Venous blood samples of all subjects were collected at five time points, after admission (T1), before surgery (T2), after protamine reversal (T3), postoperative 6 h (T4), and postoperative 24 h (T5), measuring the concentrations of platelet factor 4 (PF4), prothrombin fragment 1 + 2 (F1+2), tissue factor (TF), tissue factor pathway inhibitor (TFPI), plasminogen activator (PA), plasminogen activator inhibitor-1 (PAI-1) and thrombin antithrombin complex (TAT) by enzyme-linked immunosorbent assays (ELISAs). RESULTS: The average age of the ATAAD group was 49.9±12.5 years old, while that of the control group was 57.0±12.1 years old. There were more patients with a smoking history, and the cardiopulmonary bypass time, aortic cross-clamp time, and preoperative left ventricular ejection fraction were higher in the ATAAD group than in the control group (P < 0.05). Additionally, preoperative fibrin degradation products (FDP) and preoperative D-dimer were higher in the ATAAD group than in the control group (P < 0.05). However, time from onset to operation, intraoperative core temperature, preoperative B-type natriuretic peptide (BNP), and left ventricular end-diastolic diameter in the ATAAD group were lower than those in the control group (P < 0.05). In contrast, however, the proportion of abnormal bicuspid aortic valves in the control group was higher (P < 0.05). TF in the ATAAD group was significantly higher at T1 (7.9±3.7 ng/mL versus 0.9±0.7 ng/mL, P < 0.05). The TFPI in the ATAAD group was higher than that in the control group at T1 and T2 (P < 0.05). Additionally, PA in the ATAAD group was higher than that in the control group at T1, T2, T3, and T5 (P < 0.05), while PA in the control group was significantly higher at T3 than at T1 (P < 0.05). There was no significant difference in PAI-1 between the two groups before surgery (P > 0.05). Nevertheless, both groups reached their peak value at T3. The platelet count and fibrinogen (FBG) in the ATAAD group decreased significantly from T1 to T2 and continued to decrease after cardiopulmonary bypass. F1+2 and TAT in the ATAAD group were higher than in the control group (P < 0.05); however, they peaked at T3. The PF4 in the ATAAD group slightly increased at T1, while PF4 at T3 was significantly higher than at T1 (P < 0.05). CONCLUSION: The changes in coagulation and fibrinolysis in the ATAAD group before surgery were very significant, which caused a large amount of fibrinogen and platelet consumption. Cardiopulmonary bypass (CPB) and a lower intraoperative core temperature exacerbated the coagulation and fibrinolysis disorder, and the pro-coagulant function of the platelets was activated after surgery. Maintaining the normal concentration of fibrinogen was helpful to correct the coagulation function disorder.

Osteoglycin knockdown promotes vascular smooth muscle cell proliferation and migration in aortic dissection via the VEGF/VEGFR2 axis.

Extracellular matrix (ECM) proteins serve a major role in the pathogenesis of aortic dissection (AD). The aim of the present study was to investigate the effect of osteoglycin (OGN), an ECM proteoglycan, on aortic dissection (AD), as well as the underlying mechanism. Thoracic aortic tissues from 20 patients with AD and healthy thoracic aortic tissue from 5 patients undergoing coronary artery bypass grafting were collected to detect OGN expression levels. Following OGN knockdown in rat aortic smooth muscle cells, cell proliferation was detected by performing Cell Counting Kit­8 and BrdU assays, cell migration was assessed by performing the wound healing assay, cell invasion was detected by performing the Transwell assay, and VEGFR/AKT signaling pathway­related protein expression levels were measured via western blotting. The results demonstrated that OGN expression was significantly downregulated in patients with AD compared with healthy controls. Compared with the si­negative control (NC) group, OGN knockdown promoted RASMC proliferation and migration. Compared with the si­NC group, OGN knockdown also significantly enhanced the phosphorylation of the downstream signaling molecules of VEGFR, including AKT and ERK1/2, in VEGF­stimulated RASMCs. Collectively, the present study indicated that OGN knockdown facilitated RASMC proliferation and migration by activating AKT and ERK1/2 signaling. Therefore, OGN may serve as a novel therapeutic target for AD.

Hybrid two-stage repair of Stanford A dissection with visceral or peripheral malperfusion.

BACKGROUND: The present study aimed to evaluate the effect of two-stage hybrid aortic repair at the distal aorta of Stanford A dissection with malperfusion. METHODS: This retrospective case series included 20 patients with Stanford A dissection administered two-stage thoracic endovascular aortic repair (TEVAR) about 1 month after central repair because of visceral or limb malperfusion. The patients were examined by computed tomography (CT) angiography at 3, 6, 12 and 24 months after operation. Recovery of malperfusion and true lumen index were evaluated during follow-up. RESULTS: Twenty patients underwent two-stage hybrid aortic repair, including 11 males and 9 females. The follow-up time was 24 ± 7 months. No intervention-related complications were observed, including stent graft-induced new re-entry tears, death, stroke and spinal cord injury. Malperfusion in all cases was corrected. The true lumen was not enlarged enough 1 month after the first surgery. Thrombosis of the false lumen was observed around the elephant trunk at the carina level and the celiac artery. Three months after second stage TEVAR, the false lumen thrombosis was resorbed; in addition, the trunk was fully expanded at the carina level, and the true lumen was enlarged at the celiac artery. CONCLUSIONS: Two-stage hybrid aortic repair for residual true lumen in the distal aorta 1 month after initial surgery is helpful for descending aorta remodeling and effective in treating malperfusion. This procedure may be a good option for patients suffering from Stanford A dissection with small true lumen in the distal aorta and malperfusion.

Commutative regulation between endothelial NO synthase and insulin receptor substrate 2 by microRNAs.

Endothelial NO synthase (eNOS) expression is regulated by a number of transcriptional and post-transcriptional mechanisms, but the effects of competing endogenous RNAs (ceRNAs) on eNOS mRNA and the underlying mechanisms are still unknown. Our bioinformatic analysis revealed three highly expressed eNOS-targeting miRNAs (miR-15b, miR-16, and miR-30b) in human endothelial cells (ECs). Among the 1103 mRNA targets of these three miRNAs, 15 mRNAs share a common disease association with eNOS. Gene expression and correlation analysis in patients with cardiovascular diseases identified insulin receptor substrate 2 (IRS2) as the most correlated eNOS-ceRNA. The expression levels of eNOS and IRS2 were coincidentally increased by application of laminar shear but reduced with eNOS or IRS2 siRNA transfection in human ECs, which was impeded by Dicer siRNA treatment. Moreover, luciferase reporter assay showed that these three miRNAs directly target the 3'UTR of eNOS and IRS2. Overexpression of these three miRNAs decreased, whereas inhibition of them increased, both mRNA and protein levels of eNOS and IRS2. Functionally, silencing eNOS suppressed the Akt signal pathway, while IRS2 knockdown reduced NO production in ECs. Thus, we identified eNOS and IRS2 as ceRNAs and revealed a novel mechanism explaining the coincidence of metabolic and cardiovascular diseases.

Global gene expression analysis combined with a genomics approach for the identification of signal transduction networks involved in postnatal mouse myocardial proliferation and development.

Mammalian cardiomyocytes may permanently lose their ability to proliferate after birth. Therefore, studying the proliferation and growth arrest of cardiomyocytes during the postnatal period may enhance the current understanding regarding this molecular mechanism. The present study identified the differentially expressed genes in hearts obtained from 24 h­old mice, which contain proliferative cardiomyocytes; 7­day­old mice, in which the cardiomyocytes are undergoing a proliferative burst; and 10­week­old mice, which contain growth­arrested cardiomyocytes, using global gene expression analysis. Furthermore, myocardial proliferation and growth arrest were analyzed from numerous perspectives, including Gene Ontology annotation, cluster analysis, pathway enrichment and network construction. The results of a Gene Ontology analysis indicated that, with increasing age, enriched gene function was not only associated with cell cycle, cell division and mitosis, but was also associated with metabolic processes and protein synthesis. In the pathway analysis, 'cell cycle', proliferation pathways, such as the 'PI3K­AKT signaling pathway', and 'metabolic pathways' were well represented. Notably, the cluster analysis revealed that bone morphogenetic protein (BMP)1, BMP10, cyclin E2, E2F transcription factor 1 and insulin like growth factor 1 exhibited increased expression in hearts obtained from 7­day­old mice. In addition, the signal transduction pathway associated with the cell cycle was identified. The present study primarily focused on genes with altered expression, including downregulated anaphase promoting complex subunit 1, cell division cycle (CDC20), cyclin dependent kinase 1, MYC proto-oncogene, bHLH transcription factor and CDC25C, and upregulated growth arrest and DNA damage inducible α in 10-week group, which may serve important roles in postnatal myocardial cell cycle arrest. In conclusion, these data may provide important information regarding myocardial proliferation and development.

Long Period and High Level of D-Dimer after Coronary Artery Bypass Grafting Surgery.

Hyper-coagulation after off-pump coronary artery bypass grafting (OPCAB) is one of the main reasons for graft thrombosis. D-dimer is closely linked to the activation of coagulation. Few studies have reported the variation range and long-term abnormal coagulation after OPCAB in the Chinese population. Our study aimed to determine the characteristics and value of D-dimer after OPCAB.In this prospective study, 265 patients who underwent OPCAB for the first time were recruited from 2011 to 2012. The D-dimer level of the patients was tested before surgery and on the 1st, 4th, and 14th day, and 1st, 2nd, and 3rd month after surgery. Clinical data in the perioperative period and during the one-year follow-up period were recorded.D-dimer level increased from day 4 after OPCAB ([1321.9 ± 36.4] µg/L), peaked at 1 month ([2839.7 ± 101.4] µg/L), and decreased to the baseline ([370.3 ± 260.2] µg/L) 3 months after surgery. No death occurred, but 25 (10%) patients suffered recurrent angina in the one-year follow-up. They had significantly higher D-dimer level at one month after OPCAB than those of patients who did not suffer from angina. Preoperative ejection fraction <50% and D-dimer level >2915 µg/L at one month after surgery were significantly associated the recurrent angina.After OPCAB, patients have a higher level of D-dimer. And this lasts for a long period (about 3 months). It may reflect a certain degree of hypercoagulable and hyperfibrinolytic state after OPCAB.

[Effect of D-dimer and tissue factor-1208D/I gene polymorphism on the prognosis of patients with off-pump coronary artery bypass grafting].

OBJECTIVE: To investigate the effect of perioperative period D-dimer and tissue factor (TF)-1208D/I gene polymorphism on the long-term prognosis of patients with off-pump coronary artery bypass grafting (OPCABG). METHODS: Retrospective analysis of the case data of the first OPCABG patients admitted to Tianjin Medical University General Hospital from May 2015 to May 2016 were enrolled. The general data, operation time, bypass number, left ventricular ejection fraction (LVEF), flow rate of 24-hour pleural effusion, intraoperative heparin dosage, combined anticoagulant and antiplatelet time, and the time of postoperative ventilator were measured. The blood biochemical indexes of 1, 4, 7, 14 days and 1, 2, 3 months after operation, perioperative complications, the level of D-dimer in the patients with different TF-1208D/I gene polymorphism, and prognosis of 1-year follow-up were recorded. The risk factors of recurrent angina 1 year after operation was analyzed by Logistic regression analysis. RESULTS: The level of plasma D-dimer was increased continuously after OPCABG, and reached a peak at 1 month after operation [1.94 (1.07, 2.70) mg/L], then decreased, and decreased to preoperative level 3 months after operation [0.20 (0.10, 0.45) mg/L]. The level of D-dimer in TF-1208II genotype was significantly higher than that in TF-1208DD genotype and TF-1208D/I genotype group at 14 days and 1 month after operation [mg/L: 4.17 (1.54, 5.09) vs. 1.91 (1.07, 2.26), 1.02 (0.91, 1.88) at 14 days; 5.12 (2.41, 6.32) vs. 1.94 (1.18, 2.70), 1.62 (0.22,1.88) at 1 month, all P < 0.05]. The results of 1-year follow-up showed that 25 patients with recurrent angina pectoris without the occurrence of myocardial infarction. The proportion of recurrent angina pectoris in TF-1208II genotype was significantly higher than that in TF-1208DD genotype and TF-1208D/I genotype group (χ2 = 0.197, P = 0.004). Logistic regression analysis showed that LVEF < 0.50 [odds ratio (OR) = 6.482, 95% confidence interval (95%CI) = 1.365-18.763, P = 0.015] and TF-1208II genotype (OR = 8.864, 95%CI = 1.613-46.743, P = 0.012) were independent risk factors for recurrent angina pectoris at 1 year after OPCABG. CONCLUSIONS: After OPCABG, the body was in a hypercoagulable state and lasted for a long time, and almost recovered 3 months after operation. LVEF < 0.50 and TF-1208 II genotype were independent risk factors of angina pectoris at 1 year after surgery.

Could Early Surgery Get Beneficial in Adult Patients with Active Native Infective Endocarditis? A Meta-Analysis.

After a thorough search through the database as PubMed database and Embase database, the clinical experimental articles have been selected out on the effects of early surgery on the treatment of active native infective endocarditis. The quality of the trials included in this study was assessed by researcher according to the Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0. A meta-analysis was carried out in terms of clinical efficacy criteria by RevMan 5.3 software. Based on the results, we cautiously conclude that early surgery used for active native infective endocarditis could reduce in-hospital mortality, follow-up mortality, and IE-related mortality.

Phosphorylation of Tudor-SN, a novel substrate of JNK, is involved in the efficient recruitment of Tudor-SN into stress granules.

Posttranslational modifications of certain stress granule (SG) proteins are closely related to the assembly of SGs, a type of cytoplasmic foci structure. Our previous studies revealed that the Tudor staphylococcal nuclease (Tudor-SN) protein participates in the formation of SGs. However, the functional significance of potential Tudor-SN modifications during stress has not been reported. In this study, we demonstrated that the Tudor-SN protein was phosphorylated at threonine 103 (T103) upon stimulation with arsenite. In addition, c-Jun N-terminal kinase (JNK) was found to be responsible for Tudor-SN phosphorylation at the T103 site. We further illustrated that either a T103A mutation or the suppression of phosphorylation of T103 by the JNK inhibitor SP600125 inhibited the efficient recruitment of Tudor-SN into SGs. In addition, the T103A mutation could affect the physical binding of Tudor-SN with the G3BP (Ras-GAP SH3 domain-binding protein) protein but not with the HuR (Hu antigen R) protein and AGTR1-3'UTR (3'-untranslated region of angiotensin II receptor, type 1) mRNA cargo. These data suggested that JNK-enhanced Tudor-SN phosphorylation promotes the interaction between Tudor-SN and G3BP and facilitates the efficient recruitment of Tudor-SN into SGs under conditions of sodium arsenite-induced oxidative stress. This finding provides novel insights into the physiological function of Tudor-SN modification.

SND1 Acts Downstream of TGFß1 and Upstream of Smurf1 to Promote Breast Cancer Metastasis.

SND1 is an AEG-1/MTDH/LYRIC-binding protein that is upregulated in numerous human cancers, where it has been assigned multiple functional roles. In this study, we report its association with the TGFß1 signaling pathway, which promotes epithelial-mesenchymal transition (EMT) in breast cancer. SND1 was upregulated in breast cancer tissues, in particular in primary invasive ductal carcinomas. Transcriptional activation of the SND1 gene was controlled by the TGFß1/Smad pathway, specifically by activation of the Smad2/Smad3 complex. The SND1 promoter region contained several Smad-specific recognition domains (RD motifs), which were recognized and bound by the Smad complex that enhanced the transcriptional activation of SND1. We found that SND1 promoted expression of the E3 ubiquitin ligase Smurf1, leading to RhoA ubiquitination and degradation. RhoA degradation in breast cancer cells disrupted F-actin cytoskeletal organization, reduced cell adhesion, increased cell migration and invasion, and promoted metastasis. Overall, our results define a novel role for SND1 in regulating breast tumorigenesis and metastasis.

Tudor staphylococcal nuclease (Tudor-SN), a novel regulator facilitating G1/S phase transition, acting as a co-activator of E2F-1 in cell cycle regulation.

Tudor staphylococcal nuclease (Tudor-SN) is a multifunctional protein implicated in a variety of cellular processes. In the present study, we identified Tudor-SN as a novel regulator in cell cycle. Tudor-SN was abundant in proliferating cells whereas barely expressed in terminally differentiated cells. Functional analysis indicated that ectopic overexpression of Tudor-SN promoted the G1/S transition, whereas knockdown of Tudor-SN caused G1 arrest. Moreover, the live-cell time-lapse experiment demonstrated that the cell cycle of MEF(-/-) (knock-out of Tudor-SN in mouse embryonic fibroblasts) was prolonged compared with wild-type MEF(+/+). We noticed that Tudor-SN was constantly expressed in every cell cycle phase, but was highly phosphorylated in the G1/S border. Further study revealed that Tudor-SN was a potential substrate of Cdk2/4/6, supportively, we found the physical interaction of endogenous Tudor-SN with Cdk4/6 in G1 and the G1/S border, and with Cdk2 in the G1/S border and S phase. In addition, roscovitine (Cdk1/2/5 inhibitor) or CINK4 (Cdk4/6 inhibitor) could inhibit the phosphorylation of Tudor-SN, whereas ectopic overexpression of Cdk2/4/6 increased the Tudor-SN phosphorylation. The underlying molecular mechanisms indicated that Tudor-SN could physically interact with E2F-1 in vivo, and could enhance the physical association of E2F-1 with GCN5 (a cofactor of E2F-1, which possesses histone acetyltransferase activity), and promote the binding ability of E2F-1 to the promoter region of its target genes CYCLIN A and E2F-1, and as a result, facilitate the gene transcriptional activation. Taken together, Tudor-SN is identified as a novel co-activator of E2F-1, which could facilitate E2F-1-mediated gene transcriptional activation of target genes, which play essential roles in G1/S transition.