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.

Transcriptomics Reveals the Effect of Thymol on the Growth and Toxin Production of Fusarium graminearum.

Fusarium graminearum is a harmful pathogen causing head blight in cereals such as wheat and barley, and thymol has been proven to inhibit the growth of many pathogens. This study aims to explore the fungistatic effect of thymol on F. graminearum and its mechanism. Different concentrations of thymol were used to treat F. graminearum. The results showed that the EC50 concentration of thymol against F. graminearum was 40 µg/mL. Compared with the control group, 40 µg/mL of thymol reduced the production of Deoxynivalenol (DON) and 3-Ac-DON by 70.1% and 78.2%, respectively. Our results indicate that thymol can effectively inhibit the growth and toxin production of F. graminearum and cause an extensive transcriptome response. Transcriptome identified 16,727 non-redundant unigenes and 1653 unigenes that COG did not annotate. The correlation coefficients between samples were all >0.941. When FC was 2.0 times, a total of 3230 differential unigenes were identified, of which 1223 were up-regulated, and 2007 were down-regulated. Through the transcriptome, we confirmed that the expression of many genes involved in F. graminearum growth and synthesis of DON and other secondary metabolites were also changed. The gluconeogenesis/glycolysis pathway may be a potential and important way for thymol to affect the growth of F. graminearum hyphae and the production of DON simultaneously.

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.

Ubiquitin-specific protease as the underlying gene biomarker for aortic stenosis.

BACKGROUND: Aortic stenosis is a common heart valvular disease whose pathological processes include an inflammatory reaction and lipid accumulation. However, its detailed pathogenesis is yet to be completely elucidated. Therefore, it is of great significance to further explore the molecular mechanisms of aortic stenosis. METHODS: Four datasets were downloaded from the Gene Expression Omnibus (GEO) database. Firstly, the differently expressed genes (DEGs) were screened between control and aortic stenosis samples. Secondly, weighted gene co-expression network analysis (WGCNA) was performed to find the highly relevant gene modules. Enrichment analysis and protein-protein interaction (PPI) networking were also performed, then Cytoscape was used to identify hub genes. Finally, the six participants (3 control participants and 3 patients with aortic stenosis) were recruited at the Tianjin Chest Hospital. In order to verify the expression level of USP14, several molecular experiments were performed, including hematoxylin-eosin (HE) staining, immunohistochemistry, immunofluorescence technology, real time-quantitative polymerase chain reaction (RT-qPCR), and western blotting. RESULTS: A total of 9636 DEGs were found between the control and aortic stenosis samples. The DEGs were mainly enriched in the autophagy-animal, cellular lipid catabolic process, apoptosis, and glycoside metabolic process categories. Eleven hub genes were identified via four different algorithms. Following verification of the patient samples, Ubiquitin-specific protease 14 (USP14) was found to be displayed at higher levels in the aortic stenosis samples. CONCLUSION: USP14 might be involved in the occurrence and development of aortic stenosis, so it would be a molecular target for early diagnosis and specific treatment of aortic stenosis. There is a significant association between the high expression of USP14 and aortic stenosis, indicating that this gene may be a genetic risk factor for aortic stenosis.

Fibrous cyst of the chordae tendineae of the mitral valve: echocardiographic appearance and literature review.

Fibrous cyst of the chordae tendineae of the mitral valve (MV) is defined as a fibrous cyst arising from the chordae tendineae of the MV. It is extremely rare and its etiology is not clear. We present a case of a cystic structure within the left ventricle. This structure is connected to the anterior MV leaflet and the posterior chordae tendineae. It moves freely, resulting in stenosis of inflow tract and outflow tract of the left ventricle. Intraoperative assessment and histopathologic examination revealed it as a fibrous cyst. Its echocardiographic appearance is unique and it must be resected immediately.

[Histopathologic features of degenerative aortic valve and its mechanisms].

OBJECTIVE: To explore the related pathogenesis of degenerative aortic valvular disease by observing the histopathological changes of aortic valves from patients with aortic degenerative stenosis and compare the results with those controls with normal aortic valves. METHODS: Between May 2009 and May 2010, 22 cases of degenerative calcified aortic valves from patients with aortic valve stenosis undergoing aortic valve replacement (14 males, 8 females, mean age: (66 ± 6) years) and 6 cases of normal aortic valves from those with dissection undergoing Bentall operation (4 males, 2 females, mean age: (43 ± 5) years) were collected. The results of hematoxylin and eosin staining and immunohistochemical examinations were used to observe the histological features of degenerative aortic valves and elucidate the related pathogenesis of degenerative aortic valvular disease. RESULTS: Degenerative aortic valve leaflets became thickened. Calcification appeared in aortic side of valve leaflets. Inflammatory infiltrate, angiogenesis, cholesterol crystals, foamy cell aggregation, diffuse and nodular calcification could be seen in subendocardial space of degenerative aortic valve leaflets. No expression of Osterix (OSX) or nuclear factor of activated T-cells 1 (NFATc1) was observed in normal valves. In contrast, the expressions of OSX and NFATc1 showed nuclear immunostaining in degenerative aortic valves. Immunohistochemical staining was graded from 0 to 3. And the expression of OSX was present in 1(4.5%), 1(4.5%), 8(36.4%) and 12 cases (54.5%) respectively in calcified areas, that of OSX in 4(18.2%), 6(27.3%), 7 (31.8%) and 5 cases (22.7%) respectively in non-calcified areas, that of NFATc1 in 1 (4.5%), 1 (4.5%), 8 (36.4%) and 12 cases (54.5%) respectively in calcified areas, that of NFATc1 in 4 (18.2%), 6 (27.3%), 8 (36.4%) and 4 cases (18.2%) respectively in non-calcified areas. The expressions of OSX and NFATc1 in calcified areas were higher than those in non-calcified areas (χ(2) = 8.320, P = 0.040 and χ(2) = 9.371, P = 0.025 respectively). CONCLUSIONS: Unlike in normal valves, inflammatory infiltrate, lipid deposition, angiogenesis and bone regulatory factors appear in degenerative aortic valves. And inflammatory infiltrate, lipid deposition, angiogenesis and ossification may be involved in the degenerative calcified aortic stenosis.

[A clinical study on organ protective effect of early high-volume hemofiltration (HVHF) in patients with multiple organ dysfunction syndrome (MODS) complicated by acute kidney injury (AKI)].

OBJECTIVE: To investigate the organ protective effect of early continuous HVHF in patients with MODS complicated by AKI. METHODS: 117 patients requested HVHF in ICU due to MODS/AKI were enrolled from June 2006 to June 2011 for clinical data collection. The patients were categorized, by RIFLE scale (R-risk of renal dysfunction, I-injury to the kidney, F-failure of kidney, L-loss of kidney function, E-end stage kidney disease), into three groups: RIFLE-R (n = 15), RIFLE-I (n = 23) and RIFLE-F (n = 79). The values of their serum creatinine (SCr), oxygenation index (PaO(2) /FiO(2) ), extravascular lung water index (EVLWI), blood lactic acid (Lac), prothrombin time (PT), aspartate aminotransferase (AST), acute physiology and chronic health evaluation II (APACHE II) score were recorded, at the beginning of, and within 72 hours after HVHF. The 90-day survival rate in each group was calculated. RESULTS: No significant difference was found between RIFLE-R and RIFLE-I group, within 72 hours after HVHF, in SCr, PaO(2) /FiO(2) , EVLWI, Lac, PT, AST, or APACHE II score. The mean values of SCr, EVLWI, Lac, PT, AST, APACHE II score, within 72 hours after HVHF in the RIFLE-F group were significantly higher in comparison with RIFLE-R, and RIFLE-I group [SCr (µmol/L): 260.50±35.51 vs. 83.61±21.07, 89.71±23.81 ; EVLWI (ml/kg): 12.18±2.11 vs. 10.94±1.50,10.76±1.92; Lac (mmol/L): 2.40±0.56 vs. 1.58±0.27, 1.68±0.35; PT (sec): 14.14±1.50 vs. 12.67±1.18, 12.51±0.94; AST (U/L): 96.19±18. 84 vs. 47.91±12.85, 56.39±13.44; APACHE II score: 20.17±2.61 vs. 17.79±2.65, 18.53±2.87, P< 0.05 or P< 0.01]; However, the PaO(2) /FiO(2) (mm Hg, 1 mm Hg = 0.133 kPa) value in RIFLE-F group was found significantly lower compared to RIFLE-R and RIFLE-I group (202.80±19.07 vs. 245.24±21.18, 250.63±25.56, P< 0.01). No statistical significant difference was found in the 90-day survival rate among RIFLE-R, RIFLE-I and RIFLE-F group (66.67%, 65.22%, 63.29%, respectively, P> 0.05). CONCLUSION: Early HVHF has protective effect against organs injury in patients with MODS and AKI.

[Screening of differential expression genes of human skin epidermal stem cells at different development stages by cDNA microarray technique].

OBJECTIVE: To analyze expression characteristics of human skin epidermal stem cell at different developmental stages, and to explore its biological significance. METHODS: Health skin samples from 28-32 w fetuses (F group), 4-12 y children (C group), and 35-55 y adult (A group) were harvested, with 10 cases in each group. Epidermis were separated using trypsin digestion and EDTA, and human epidermal stem cells were isolated and purified with type IV collagen attachment method. The monoclonal antibody of integrin beta1 and keratin 19 were used for detection and identification of epidermal stem cells by immunohistochemical staining. Total RNA was extracted from above cells by Trizol one-step method, and were detected by formaldehyde denaturing agarose gel electrophoresis. Probes were prepared and hybridized into cDNA microarray for scanning fluorescent signals and analysis of images, with two-fold differential expression value for screening. Significantly up/down-regulated genes were selected for verification by real time RT-PCR. RESULTS: By comparing expression profile between A and C groups, a total of 1808 genes with differential expression were detected, including 1089 up-regulated genes and 719 down-regulated genes, and they were classified into 128 categories. Among them, 1462 genes were known (found in GeneBank), 346 genes were unknown. A total of 4534 genes with differential expression were detected between C and F groups, in which 1783 genes were up-regulated and 2751 genes were down-regulated, and they were classified into 216 categories. Among them, 3577 genes were known (found in GeneBank), and 957 genes were unknown. There were 1104 genes with differential expression consistently detected in F, C and A groups, which were classified into 32 categories according to gene function. Among them, 94 genes were consistently up-regulated and 75 genes consistently down-regulated. Test results of real time RT-PCR were in accordance with above-mentioned results. CONCLUSIONS: Gene expression profiles of epidermal stem cells cultured in vitro, harvested from fetuses, children, and adult, exhibit obvious difference. This may be closely related to different stages of proliferation and differentiation of human epidermal stem cell and self-repair ability of wound at different developmental stages.

[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.