NDUFB11 and NDUFS3 regulate arterial atherosclerosis and venous thrombosis: Potential markers of atherosclerosis and venous thrombosis.

Atherosclerosis is a chronic disease that thickens the blood vessel walls and narrows the lumen. Venous thrombosis is a blood clot that forms in the body's deep veins or pulmonary arteries. However, the relationship between NDUFB11 and NDUFS3 and atherosclerosis and venous thrombosis is unclear. We employed data files that combined atherosclerosis and chronic stress groups. Subsequently, we conducted differential gene expression analysis (DEGs) and performed weighted gene co-expression network analysis (WGCNA). We constructed and analyzed a protein-protein interaction (PPI) network. Further analyses included functional enrichment analysis, gene set enrichment analysis (GSEA), gene expression heatmaps, immune infiltration analysis, and mRNA analysis. By comparing our findings with the Comparative Toxicogenomics Database (CTD), we identified the most relevant diseases associated with the core genes. Additionally, we utilized TargetScan to screen for miRNAs regulating the central DEGs. To validate our results, we conducted Western Blot experiments at the cellular level. A total of 1747 DEGs were co-identified. According to the Gene Ontology (GO) analysis of differentially expressed genes, they were primarily enriched in mitochondrial gene expression, mitochondrial envelope, organelle membrane, and mitochondrial inner membrane categories. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the target cells were mainly enriched in metabolic pathways, ribosomes, and histidine metabolism. The intersection of enriched terms from both GO and KEGG analyses showed significant enrichment in mitochondrial gene expression, mitochondrial envelope, organelle inner membrane, ribosomal structural constituents, histidine metabolism, and oxidative phosphorylation. Eight core genes were identified, including NDUFS5, UQCRQ, COX6C, COX7B, ATP5ME, NDUFS3, NDUFA3, and NDUFB11. The gene expression heatmap demonstrated that core genes (NDUFB11 and NDUFS3) were downregulated in atherosclerosis with venous thrombosis samples and upregulated in normal samples. CTD analysis revealed that the core genes NDUFB11 and NDUFS3 were associated with pain, arterial diseases, atherosclerosis, arteritis, venous thrombosis formation, and venous thromboembolism. We added Western Blot basic cell experiment for verification. NDUFB11 and NDUFS3 are downregulated in atherosclerosis and venous thrombosis, associated with poorer prognosis, and may serve as potential biomarkers for both diseases.

NDUFB11 and NDUFS3 play a role in atherosclerosis and chronic stress.

OBJECTIVE: Atherosclerosis is characterized by the formation of fibrofatty plaques in the intima of arteries, resulting in thickening of the vessel wall and narrowing of the lumen. Chronic stress refers to individuals in a state of long-term chronic stress. However, the relationship between NDUFB11 and NDUFS3 and atherosclerosis and chronic stress is unclear. METHOD: The atherosclerosis with chronic stress group data file was used. DEGs were screened and WGCNA was performed. Construction and analysis of PPI Network. Functional enrichment analysis, GSEA, gene expression heatmap, immune infiltration analysis and mRNA analysis were performed. CTD was used to find diseases most related to core genes. WB was performed. TargetScan was used to screen miRNAs of DEGs. RESULTS: 1708 DEGs were identified. According to GO analysis, they were mainly enriched in catabolic processes, organic acid metabolism processes, carboxylic acid metabolism processes. KEGG analysis showed that they were mainly enriched in metabolic pathways, fatty acid metabolism, pentose phosphate pathway, glycolysis / gluconeogenesis, fructose and mannose metabolism. Gene expression heatmap showed that the core genes (NDUFB11, NDUFS3) were lowly expressed in samples of those with atherosclerosis accompanied by chronic stress and highly expressed in the normal samples. NDUFB11 and NDUFS3 were associated with necrosis, hyperplasia, inflammation, renal disease, weight loss, memory impairment, and cognitive impairment. WB showed that the expression level of NDUFS3 in atherosclerosis and chronic stress was lower than that in control group. CONCLUSIONS: NDUFB11 and NDUFS3 are underexpressed in atherosclerosis and chronic stress; the lower NDUFB11 and NDUFS3 levels, the worse the prognosis.

The protective role and mechanism of liriodendrin in rats with myocardial infarction.

BACKGROUND: Liriodendrin is a therapeutic constituent of sargentgloryvine stem which is a famous Chinese traditional medicine. Previous studies have suggested liriodendrin could inhibit different pathways to treat inflammation in lung and intestinal tract. But whether it can treat myocardial infarction (MI) is unknown. We investigated the protective effect of liriodendrin on acute MI in rats and explored the specific mechanisms to expand the use of this traditional Chinese medicine. METHODS: The rats were randomized into the sham group (sham operation), control group (ligation of the left anterior descending artery), and liriodendrin group. The liriodendrin group was intragastrically administered with a liriodendrin solution (100 mg/kg). The control group and the sham group were intragastrically administered with normal saline. Before all rats were euthanized, echocardiography was used to detect their cardiac function. Hematoxylin and eosin (HE) staining and the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) method were performed. Further quantitative detection of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) levels in tissues were also detected. Western Blot and real-time polymerase chain reaction (RT-PCR) were used to detect the apoptosis and nuclear factor kappa-B (NF-κB) pathway in tissues. H9C2 cells were used to detect the related mechanisms in vitro. RESULTS: Echocardiography showed that, compared to control group, the cardiac function of the liriodendrin group was significantly improved. histopathological staining of the control group showed that the myocardial tissue was severely damaged, and inflammatory cells were infiltrated. Compared to the control group, the apoptosis index of the liriodendrin group was significantly lower (P<0.05). Enzyme-linked immunosorbent assay (ELISA) results showed that the levels of IL-1ß and TNF-α in the control group were higher than those in the liriodendrin group (P<0.05). Meanwhile, apoptosis and the NF-κB pathway were inhibited after liriodendrin administration (P<0.05). Moreover, the mRNA transcriptional activity in the control group was also higher than that in the liriodendrin group (P<0.05). Because of the effect of liriodendrin, NF-κB pathway and apoptosis were downregulated in H9C2 cells which were exposed to ischemia-hypoxia. CONCLUSIONS: Liriodendrin may protect myocardial cells after myocardial infarction in rats by inhibiting the release of inflammatory factors, activation of the NF-κB pathway, and apoptosis.

Risk factors of continuous renal replacement therapy following total aortic arch replacement under moderate hypothermia.

BACKGROUND: Stanford type A aortic dissection (TAAD) has a sudden onset and high mortality, and emergency total aortic arch replacement (TAAR) is the main treatment option for TAAD. The mortality rate of patients with postoperative acute kidney injury (AKI) combined with continuous renal replacement therapy (CRRT) is remarkable higher than that of patients without AKI. However, incidence of AKI and risk factors for CRRT following TAAR isn't entirely understood. METHODS: From October 2018 to March 2021, all patients with Stanford type A dissection who underwent total arch replacement surgery under MHCA were enrolled. According to whether CRRT treatment was performed, participants were divided into a CRRT group (n=49) and control group (n=72). Both groups incorporated the brain protection strategy of moderate hypothermia, and the left common carotid artery and the innominate artery were perfused anteriorly. Relevant medical data was collected. RESULTS: Age, gender, and a history of smoking and drinking were not significantly different between the 2 groups (P>0.1). There were statistical differences between the 2 groups in aortic sinus diameter and Bentall procedure (P≤0.05). Univariate analysis revealed that fresh frozen plasma was a protective factor (P<0.05) and the intraoperative transfusion volume of red blood cells, platelets, fresh frozen plasma, autologous blood used for intraoperative bleeding, aortic sinus diameter, and Bentall procedure were risk factors (P<0.1). Multivariate analysis showed that the Bentall procedure and intraoperative bleeding were risk factors for CRRT (P<0.05), and the aortic sinus diameter and intraoperative transfusion score were also risk factors for CRRT (P<0.05). Receiver operating characteristic (ROC) analysis demonstrated that the model of aortic sinus diameter and intraoperative transfusion score had more significantly different discriminatory powers. CONCLUSIONS: The Bentall procedure, intraoperative bleeding, aortic sinus diameter, and intraoperative transfusion score were risk factors for postoperative CRRT. The model of aortic sinus diameter and intraoperative transfusion score had more significantly different discriminatory powers.

Mechanism of action of resolvin D1 in inhibiting the progression of aortic dissection in mice.

BACKGROUND: To investigate the protective effect of resolvin D1 (RvD1) on aortic dissection (AD) in mice and explore the related mechanisms. METHODS: Mice were randomly divided into a blank group, model group, and RvD1 group. The RvD1 and model groups were administered 0.4% ß-aminopropionitrile (BAPN) solution, while the blank group was administered distilled water. When the experiment began, whether mice had AD was determined by echocardiogram. The RvD1 group was also administered RvD1 (30 µg/kg), while the model and blank groups were administered saline intraperitoneally. After 21 d, body weight trend and survival rate in the three groups were compared. The diameter of the ascending aorta of mice was detected by echocardiography. Then, the mice were sacrificed, and histopathological staining procedures were performed. Enzyme-linked immunosorbent assay (ELISA) was used to detect cytokines and chemokines in blood and tissue, respectively. RESULTS: At 21 d, there was no statistically significant difference in body weight between three groups (P>0.05). The survival rate showed a significant difference between the RvD1 and model group (P<0.05). Echocardiography revealed that compared with the RvD1 and blank groups, aortic dilatation was significant in the model group. Pathological staining showed that the destruction of the aortic wall structure and inflammatory cell infiltration were more noticeable in the model group than in the RvD1 group. A slight disintegration of elastic fibers and collagen in the aorta was observed in the RvD1 group, and the aortic structure was clear. The results of ELISA showed that the inflammatory factors levels in the RvD1 group, although higher than those in blank group, were significantly decreased compared with the model group. The ELISA results of AD tissue showed that at 21 d, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in the aorta were significantly decreased in the RvD1 group compared with the model group (P<0.05). CONCLUSIONS: Administration of RvD1 significantly delayed aortic dilation and disintegration and inhibited local macrophage and neutrophil infiltration in the early stages of aortic injury. Moreover, RvD1 significantly downregulated the expression of cytokines and chemokines in aortic tissues and serum and improved aortic remodeling.

BPI and KIR6.1 as significant hub genes for vein graft restenosis.

BACKGROUND: Vein graft restenosis (VGR), which appears to be caused by dyslipidemia following vascular transplantation, seriously affects the prognosis and long-term quality of life of patients. METHODS: This study analyzed the genetic data of restenosis (VGR group) and non-stenosis (control group) vessels from patients with coronary heart disease post-vascular transplantation and identified hub genes that might be responsible for its occurrence. GSE110398 was downloaded from the Gene Expression Omnibus database. A repeatability test for the GSE110398 dataset was performed using R language. This included the identification of differentially expressed genes (DEGs), enrichment analysis via Metascape software, pathway enrichment analysis, and construction of a protein-protein interaction network and a hub gene network. RESULTS: Twenty-four DEGs were identified between VGR and control groups. The four most important hub genes (KIR6.1, PCLP1, EDNRB, and BPI) were identified, and Pearson's correlation coefficient showed that KIR6.1 and BPI were significantly correlated with VGR. KIR6.1 could also sensitively predict VGR (0.9 < area under the curve ≤1). CONCLUSION: BPI and KIR6.1 were differentially expressed in vessels with and without stenosis after vascular transplantation, suggesting that these genes or their encoded proteins may be involved in the occurrence of VGR.

Effects of Autologous Platelet Rich Plasma on Intraoperative Transfusion and Short-Term Outcomes in Total Arch Replacement (Sun's Procedure): A Prospective, Randomized Trial.

OBJECTIVE: To observe the effect of collecting and retransfusing autologous platelet rich plasma (aPRP) on the amount of allogeneic blood usage in total arch replacement (Sun's surgery) and the outcomes 30 days after surgery. DESIGN: A prospective, randomized trial. SETTING: A tertiary university hospital specialized in cardiovascular diseases. PARTICIPANTS: The study comprised 120 patients undergoing Sun's surgery for Stanford type A acute aortic dissection. INTERVENTIONS: aPRP was harvested before incision and was re-transfused after heparin neutralization for patients in the treatment group. MEASUREMENTS AND MAIN RESULTS: There was no significant difference in preoperative demographic data between the 2 study groups. Intraoperative transfusions of erythrocyte (p = 0.009), plasma (p = 0.017), cryoprecipitate (p = 0.002), and platelets (p < 0.001) in the treatment group were reduced significantly. In addition, less blood loss was observed in the treatment group (p = 0.002). The durations of postoperative mechanical ventilation (p = 0.029) and hospitalization (p = 0.002) of the treatment group were significantly shorter. There were no statistically significant differences in the length of intensive care unit stay, the incidence of complications, and mortality 30 days after surgery. CONCLUSION: In total arch replacement (Sun's surgery), collecting and retransfusing aPRP reduced intraoperative transfusions of erythrocyte, plasma, and cryoprecipitate and decreased the duration of postoperative mechanical ventilation and hospitalization. This technique had no significant effect on the incidence of complications and mortality 30 days postoperatively.

Protective effects of N(2)­L­alanyl­L­glutamine mediated by the JAK2/STAT3 signaling pathway on myocardial ischemia reperfusion.

To explore the protective effect of N(2)-L-alanyl-L-glutamine (NLAG) on myocardial ischemia-reperfusion injury (IRI), and observe the influence of NLAG on the Janus activated kinase signal transducer 2 and activator of transcription 3 (JAK2/STAT3) signaling pathway­associated molecules. Wistar rats were randomly divided into three groups: Sham, IRI and NLAG. In the IRI rat model, the cardiac hemodynamics, the maximum rate of left ventricular pressure (+dP/dtmax) and the left ventricular end­diastolic pressure (LVDP) were recorded. Hematoxylin­eosin and Masson staining were used to detect myocardial histological changes. The levels of plasma interleukin (IL)­1ß and ­6, tumor necrosis factor (TNF)­α, lactase dehydrogenase (LDH), troponin (cTn)I, creatine kinase (CK), heart type fatty acid binding protein (hFABP), malondialdehyde (MDA) and succinate dehydrogenase (SDH) were determined with ELISA. The protein expression levels of B­cell lymphoma (Bcl)­2, Bcl2­associated X protein (Bax), Caspase­3, JAK2, phosphorylated (p)­JAK2, STAT3 and p­STAT3 were detected by western blot analysis. The IRI model demonstrated notable myocardial injury; myocardial cells were arranged disorderly with some nuclei disappearing, and cardiac muscular fibers were degenerated. Following 60 min of reperfusion, LVDP, HR and +dP/dtmax were 31.3±4.53 mmHg, 239.17±8.45 beats/min and 615.17 mmHg/sec, respectively. Compared with the Sham group, the levels of LDH, cTnI, CK, hFABP release, inflammatory factors (IL­1ß, IL­6 and TNF­α) and oxygen free radical (MDA and SDH) levels were increased in the IRI group. In the NLAG group, myocardial injury was improved, the concentrations of LDH, cTnI, CK, hFABP, IL­1ß, IL­6, TNF­α, MDA were decreased, and SDH release was increased compared with the IRI group. In addition, NLAG significantly increased Bcl­2, JAK2, p­JAK2, STAT3 and p­STAT3 protein expression, and decreased Bax protein expression compared with the IRI group. In conclusion, myocardial ischemia­reperfusion can lead to myocardial cell apoptosis and myocardial injury and NLAG attenuates the IRI­induced mitochondrial oxidative stress injury and apoptosis by activating the JAK2/STAT3 signaling pathway, thus exerting protective effects against IRI.

[Clinical efficacy of malignant obstructive jaundice treated by domestic biliary metallic stent insertion].

OBJECTIVE: To evaluate the clinical efficacy of implanted biliary metallic stents in the management of malignant obstructive jaundice (MOJ). METHODS: Percutaneous transhepatic cholangiography and stent insertion were performed in 241 consecutive patients to treat malignant biliary obstruction between December 1998 and February 2009. The study end point was patient death. All patients were followed-up until death or until February 2010. The therapeutic efficacy was determined by statistical analysis of life span and pre- and post-operative laboratory indices. RESULTS: All 241 patients were successfully stented. The level of bilirubin descended obviously within four weeks of implantation (P less than 0.05), and the early mortality rate was 4.56% (11/241). Two-hundred-and-two patients were followed-up (range: 8-193 weeks post-transplantation) and showed a median survival of 43.55 weeks. The survival rates at 13, 26, 39 and 52 weeks post-transplantation were 87%, 66%, 56%, and 41%, respectively. The stent patency rates at 13, 26, 39 and 52 weeks post-transplantation were 70%, 46%, 36% and 24%, respectively; the mean stent patency was 27.57 weeks. Cox regression analysis identified the strong predictors of improved survival as an initial bilirubin level of less than 221 mumol/L (P = 0.01) and a stent-induced bilirubin reduction of more than 50% (P = 0.002). CONCLUSION: Transhepatic metallic biliary stenting is a safe and effective therapeutic intervention for malignant biliary obstruction. Significant periods of survival and palliation of jaundice can be achieved with this method. Hyperbilirubinemia and a stent-induced bilirubin reduction of less than 50% are independent predictive factors for the survival of MOJ patients.

[Analysis of risk factors in elderly patients with renal dysfunction undergoing off-pump coronary artery bypass grafting].

OBJECTIVE: To analyze the risk factors in the patients over 65 years old undergoing off-pump coronary artery bypass grafting (OPCAG) as grouped by postoperative creatinine clearance rate (Ccr). METHODS: A total of 462 consecutive patients over 65 years old undergoing OPCAG from January 2007 to December 2008 were recruited. They were divided into 3 groups by renal functions: normal, minor injury and moderate-severe injury. The risk factors were analyzed by a comparison of postoperative complications, duration of intubation, stay of intensive care unit and mortality rate, et al. RESULTS: There was no significant difference between the parameters of preoperative complications, left ventricle ejection fraction (LVEF), left ventricle end diastolic diameter (LVEDD) and lipid level, et al. And the postoperative complications were closely related to the decrease of Ccr and the increases of B-type natriuretic peptide (BNP), CKMB, total bilirubin (TBIL) and LVEDD (P < 0.01 for each). CONCLUSIONS: The moderate-severe renal injury (Ccr < 50 ml/min) with the abnormal levels of TBIL, BNP and LVEDD are the risk factors for a worse prognosis in OPCAG patients over 65 years old. Because of the injury of OPCAG, we should pay attention to patients with abnormal renal function (Ccr < 80 ml/min) to prevent an onset of severe complications.