SLC3A2 promotes tumor-associated macrophage polarization through metabolic reprogramming in lung cancer.

Tumor-associated macrophages (TAMs) are one of the most abundant immunosuppressive cells in the tumor microenvironment and possess crucial functions in facilitating tumor progression. Emerging evidence indicates that altered metabolic properties in cancer cells support the tumorigenic functions of TAMs. However, the mechanisms and mediators the underly the cross-talk between cancer cells and TAMs remain largely unknown. In the present study, we revealed that high solute carrier family 3 member 2 (SLC3A2) expression in lung cancer patients was associated with TAMs and poor prognosis. Knockdown of SLC3A2 in lung adenocarcinoma cells impaired M2 polarization of macrophages in a coculture system. Using metabolome analysis, we identified that SLC3A2 knockdown altered the metabolism of lung cancer cells and changed multiple metabolites, including arachidonic acid, in the tumor microenvironment. More importantly, we showed that arachidonic acid was responsible for SLC3A2-mediated macrophage polarization in the tumor microenvironment to differentiate into M2 type both in vitro and in vivo. Our data illustrate previously undescribed mechanisms responsible for TAM polarization and suggest that SLC3A2 acts as a metabolic switch on lung adenocarcinoma cells to induce macrophage phenotypic reprogramming through arachidonic acid.

Effects of Synthetic Astaxanthin on the Growth Performance, Pigmentation, Antioxidant Capacity, and Immune Response in Black Tiger Prawn (Penaeus monodon).

Synthetic astaxanthin is an effective nutritional strategy for improving shrimp body color and promoting growth. However, the optimal amount of astaxanthin in feed also varies with the synthetic technology and purity. In the present study, five diets containing different doses of synthetic astaxanthin (0% (CON), 0.02% (AX0.02), 0.04% (AX0.04), 0.08% (AX0.08), and 0.16% (AX0.16)) were administered to Penaeus monodon (initial body weight: 0.3 ± 0.03 g) for 8 weeks. With an increase in astaxanthin content in feed, weight gain and specific growth rate increased initially and subsequently decreased, with the highest value appearing at AX0.08. Dietary astaxanthin supplementation obviously improved the carapace and muscle color by enhancing astaxanthin pigmentation. Meanwhile, the fatty acid profile was altered by dietary astaxanthin, as evidenced by a decline in palmitic acid proportion, along with an increase in n-3 polyunsaturated fatty acids (n-3 PUFA) contents in muscle. In addition, dietary astaxanthin supplementation regulated prawn's antioxidant capacity. In the hemolymph, the activities of glutamic pyruvic transaminase (GPT) showed a significantly decrease trend with linear effect. The activities of glutamic oxaloacetic transaminase (GOT) and the contents of malondialdehyde (MDA) were first downregulated and then upregulated with significantly quadratic pattern. In the hepatopancreas, the activities of superoxide dismutase (SOD) and the contents of MDA were significantly downregulated with the increase of dietary astaxanthin levels. Reduced glutathione (GSH) contents and catalase (CAT) activities were also significantly decreased in group AX0.08. Correspondingly, astaxanthin decreased GSH and MDA contents under transportation stress. Moreover, the mRNA expression of immune genes (traf6, relish, and myd88) were inhibited by dietary astaxanthin supplementation. Based on the results of polynomial contrasts analysis and Duncan's test, dietary synthetic astaxanthin is a suitable feed additive to improve the growth, body color, antioxidant capacity, and nonspecific immunity of P. monodon. According to the second-order polynomial regression analysis based on the weight gain, the optimal supplementation level of dietary astaxanthin was 90 mg kg-1 in P. monodon.

Heat map visualization for electrocardiogram data analysis.

BACKGROUND: Most electrocardiogram (ECG) studies still take advantage of traditional statistical functions, and the results are mostly presented in tables, histograms, and curves. Few papers display ECG data by visual means. The aim of this study was to analyze and show data for electrocardiographic left ventricular hypertrophy (LVH) with ST-segment elevation (STE) by a heat map in order to explore the feasibility and clinical value of heat mapping for ECG data visualization. METHODS: We sequentially collected the electrocardiograms of inpatients in the First Affiliated Hospital of Shantou University Medical College from July 2015 to December 2015 in order to screen cases of LVH with STE. HemI 1.0 software was used to draw heat maps to display the STE of each lead of each collected ECG. Cluster analysis was carried out based on the heat map and the results were drawn as tree maps (pedigree maps) in the heat map. RESULTS: In total, 60 cases of electrocardiographic LVH with STE were screened and analyzed. STE leads were mainly in the V1, V2 and V3 leads. The ST-segment shifts of each lead of each collected ECG could be conveniently visualized in the heat map. According to cluster analysis in the heat map, STE leads were clustered into two categories, comprising of the right precordial leads (V1, V2, V3) and others (V4, V5, V6, I, II, III, aVF, aVL, aVR). Moreover, the STE amplitude in 40% (24 out of 60) of cases reached the threshold specified in the STEMI guideline. These cases also could be fully displayed and visualized in the heat map. Cluster analysis in the heat map showed that the III, aVF and aVR leads could be clustered together, the V1, V2, V3 and V4 leads could be clustered together, and the V5, V6, I and aVL leads could be clustered together. CONCLUSION: Heat maps and cluster analysis can be used to fully display every lead of each electrocardiogram and provide relatively comprehensive information.

[Targeting EGFRvIII for treatment of glioblastoma: From molecular mechanisms to clinical strategies].

Glioblastoma is one of the most common intracranial malignant tumor and its initiation and progression are closely associated with epidermal growth factor receptor (EGFR). EGFR variant III (EGFRvIII) is a mutant EGFR and highly expressed in glioblastoma. EGFRvIII promotes the proliferation and invasiveness of glioblastoma cells and induces drug resistance by signaling networks.

Chinese medicine for mental disorder and its applications in psychosomatic diseases.

With the development of modern medicine, an increasing awareness has developed regarding the limitations of a specialized and compartmentalized approach to clinical practice that largely ignores the interconnectedness of the mind, body, and spirit. Although contemporary medicine now accepts this interconnectedness, practitioners tend to think that the emotions play a secondary or excitatory role in producing disease rather than being a primary causative factor. Traditional Chinese medicine (TCM), which stems from Confucianism, Buddhism, and Daoism, views the body and the spirit as inseparable. This construct provides the foundation for the whole system of TCM, and therefore constitutes the backbone of TCM. This article presents the ways in which emotion can act as an internal etiological factor that produces a pathogenic mechanism and that underlies various psychosomatic diseases. Therefore, this article intends to integrate the ancient classic treatise established in the Yellow Emperor's Canon of Internal Medicine with current data. Likewise, the authors discuss their empirical experience to illustrate the following concepts: (1) the factors contributing to emotional impairment; (2) the holistic approach to diagnosing psychosomatic disease; (3) the integrative therapy necessary to restore the balance of body and mind; and (4) the role of emotional theory in nursing care and the prevention of psychosomatic disease.

Excessive Substitution of Fish Meal with Fermented Soybean Meal Induces Oxidative Stress by Impairing Glutathione Metabolism in Largemouth Bass (Micropterus salmoides).

The application of fermented soybean meal (FSBM) is an effective strategy to alleviate the shortage of fish meal (FM) in aquaculture. However, an excessive substitution ratio often reduces fish growth and induces liver oxidative stress, while the mechanism remains poorly understood. Here, an 8-week feeding trial was conducted in largemouth bass (initial weight: 6.82 ± 0.09 g) to establish an oxidative stress model by replacing 50% of FM with FSBM (fermented by Bacillus subtilis). The results showed that FSBM substitution significantly reduced the growth performance of largemouth bass, including the weight gain rate and specific growth rate. Moreover, FSBM significantly reduced the contents of essential amino acids and total free amino acids in muscle, along with the mRNA expression of amino acids and small peptide transporters. Enzyme activity detection and liver sections showed that FSBM substitution caused liver oxidative stress, indicating the successful construction of an oxidative stress model. An integrated analysis of transcriptomic and metabolomic data revealed that FSBM substitution impaired glycine, serine and threonine metabolism, as well as glutathione metabolism. In addition, the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) was decreased in the FSBM group, which may explain the mechanism of oxidative stress caused by FSBM substitution. Considering that glycine is an important component of glutathione synthesis, key genes involved in glycine metabolism (glya, gnmt and agxt) and dietary glycine supplementation should be valued to improve the availability of FSBM. This study reveals for the first time the importance of non-essential amino acids in improving the utilization of plant-based protein sources and provides original insight for the optimization of aquatic feeds.

Antibody-array interaction mapping, a new method to detect protein complexes applied to the discovery and study of serum amyloid P interactions with kininogen in human plasma.

Protein-protein interactions are fundamentally important in biological processes, but the existing analytical tools have limited ability to sensitively and precisely measure the dynamic composition of protein complexes in biological samples. We report here the development of antibody-array interaction mapping (AAIM) to address that need. We used AAIM to probe interactions among a set of 48 proteins in serum and found several known interactions as well potentially novel interactions, including multiprotein clusters of interactions. A novel interaction initially identified between the innate immune system protein C-reactive protein and the inflammatory protein kininogen (KNG) was confirmed in subsequent experiments to involve serum amyloid P instead of its highly related family member, C-reactive protein. AAIM was used in a variety of formats to further study this interaction. In vitro studies confirmed the ability of the purified proteins to interact and revealed a zinc dependence of the interaction. Studies using plasma samples collected longitudinally following a controlled myocardial infarction revealed no consistent changes in the serum amyloid P-KNG interaction levels but consistent changes in KNG activation and interactions with plasma prekallikrein. These results demonstrate a versatile platform for measuring the dynamic composition of protein complexes in biological samples that should have value for studies of normal and disease-related signaling networks, multiprotein clusters, or enzymatic cascades.

Girdin Promotes Tumorigenesis and Chemoresistance in Lung Adenocarcinoma by Interacting with PKM2.

Girdin, an Akt substrate, has been reported to promote tumorigenesis in various tumors. However, the role of Girdin in a spontaneous tumor model has not yet been explored. Here, we studied the role of Girdin in lung adenocarcinoma (LUAD) using the autochthonous mouse model and found that Girdin led to LUAD progression and chemoresistance by enhancing the Warburg effect. Mechanistically, Girdin interacted with pyruvate kinase M2 (PKM2), which played a vital role in aerobic glycolysis. Furthermore, Girdin impaired Platelet Derived Growth Factor Receptor Beta (PDGFRß) degradation, which in turn, promoted PKM2 tyrosine residue 105 (Y105) phosphorylation and inhibited PKM2 activity, subsequently promoting aerobic glycolysis in cancer cells. Taken together, our study demonstrates that Girdin is a crucial regulator of tumor growth and may be a potential therapeutic target for overcoming the resistance of LUAD cells to chemotherapy.

A Novel Integrated Metabolism-Immunity Gene Expression Model Predicts the Prognosis of Lung Adenocarcinoma Patients.

Background: Although multiple metabolic pathways are involved in the initiation, progression, and therapy of lung adenocarcinoma (LUAD), the tumor microenvironment (TME) for immune cell infiltration that is regulated by metabolic enzymes has not yet been characterized. Methods: 517 LUAD samples and 59 non-tumor samples were obtained from The Cancer Genome Atlas (TCGA) database as the training cohort. Kaplan-Meier analysis and Univariate Cox analysis were applied to screen the candidate metabolic enzymes for their role in relation to survival rate in LUAD patients. A prognostic metabolic enzyme signature, termed the metabolic gene risk score (MGRS), was established based on multivariate Cox proportional hazards regression analysis and was verified in an independent test cohort, GSE31210. In addition, we analyzed the immune cell infiltration characteristics in patients grouped by their Risk Score. Furthermore, the prognostic value of these four enzymes was verified in another independent cohort by immunohistochemistry and an optimized model of the metabolic-immune protein risk score (MIPRS) was constructed. Results: The MGRS model comprising 4 genes (TYMS, NME4, LDHA, and SMOX) was developed to classify patients into high-risk and low-risk groups. Patients with a high-risk score had a poor prognosis and exhibited activated carbon and nucleotide metabolism, both of which were associated with changes to TME immune cell infiltration characteristics. In addition, the optimized MIPRS model showed more accurate predictive power in prognosis of LUAD. Conclusion: Our study revealed an integrated metabolic enzyme signature as a reliable prognostic tool to accurately predict the prognosis of LUAD.

Diagnostic Value of Serum Concentration of Galectin-3 in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Although the predictive value of galectin-3 for heart failure with preserved ejection fraction has been demonstrated, the diagnostic value remains unclear. The present study was performed to address this issue. HYPOTHESIS: Galectin-3 has diagnostic value for heart failure with preserved ejection fraction. METHODS: This is a diagnostic experiment. We conducted an observational study of 223 patients with combined symptoms of heart failure and diseases that can lead to heart failure with preserved ejection fraction. Patients were grouped into the heart failure group and control group in accordance with the 2016 European Society of Cardiology heart failure guidelines for heart failure with preserved ejection fraction. Baseline information and serum galectin-3 concentration were assessed within 24 h after admission. RESULTS: Serum galectin-3 concentration was significantly higher in the heart failure group compared with the control group. Binary logistic regression analysis showed that higher galectin-3 concentration was associated with the occurrence of heart failure with preserved ejection fraction. The area under the curve of galectin-3 was 0.763, indicating that galectin-3 has moderate diagnostic value for heart failure with preserved ejection fraction. Galectin-3 >15.974 ng/mL identified heart failure with preserved ejection fraction with 76.0% sensitivity and 71.9% specificity. CONCLUSIONS: There was a correlation between galectin-3 and heart failure with preserved ejection fraction, and galectin-3 was an independent predictor of heart failure with preserved ejection fraction. The diagnostic value of galectin-3 for heart failure with preserved ejection fraction was moderate (AUC: 0.763, 95% CI: 0.696-0.821, P < 0.01, and the sensitivity is 76.0% while the specificity is 71.9% at the threshold 15.974 ng/mL) and was higher than that of interventricular septal thickness or E/A ratio.

Suppression of DLBCL Progression by the E3 Ligase Trim35 Is Mediated by CLOCK Degradation and NK Cell Infiltration.

The majority of diffuse large B-cell lymphoma (DLBCL) patients develop relapsed or refractory disease after standard ruxolitinib, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy, which is partly related to a dysregulated tumor immune microenvironment. However, how the infiltration of immune cells is appropriately regulated is poorly understood. Herein, we show that the E3 ubiquitin ligase Trim35 is expressed at low levels in human DLBCL tissues. We also show that overexpression of Trim35 suppresses DLBCL cell proliferation and correlates with inferior survival in DLBCL patients. Our mechanistic study shows that Trim35 functions as an E3 ligase to mediate the ubiquitination and degradation of CLOCK, a key regulator of circadian rhythmicity. High expression of Trim35 correlates with NK cell infiltration in DLBCL, partly due to the degradation of CLOCK. Consistently, patients with high expression of CLOCK show poor overall survival. Overall, these findings suggest that Trim35 suppresses the progression of DLBCL by modulating the tumor immune microenvironment, indicating that it may be a promising diagnostic and prognostic biomarker in DLBCL.

Analysis of glycans on serum proteins using antibody microarrays.

Antibody arrays can be employed for the profiling glycan structures on proteins. Antibody arrays capture multiple, specific proteins directly from biological samples (such as serum), and lectin and glycan-binding antibodies probe the levels of specific glycans on the captured proteins. We use a practical method of partitioning microscope slides to enable the convenient processing of many detection reagents or samples. A critical first step in the procedure is the chemical derivatization of the glycans on the spotted capture antibodies, which prevents lectin binding to those glycans. We describe those methods along with the methods for preparing and treating serum samples, running the experiments, and designing and interpreting the experiments.

Hypoxia-inducible factor-1alpha induces the coronary collaterals for coronary artery disease.

BACKGROUND: Marked variability exists in coronary artery collaterals in patients with ischemic heart disease. Multiple factors are thought to play a role in collateral development; however, the contribution of hypoxia inducible factor-1alpha (HIF-1alpha), which is a transcriptional activator that functions as a master regulator of oxygen homeostasis, is not completely clear. It could play an important role in modulating collateral development. OBJECTIVE: The objective of this study is to investigate the changes and significance of expression of HIF-1alpha in patients with coronary artery collaterals. METHODS: Collateral vessels were determined in 98 patients with >or=70% narrowing of at least one coronary artery without earlier revascularization, 42 patients with coronary artery collaterals and 56 patients with no coronary artery collaterals. Extent of collaterals was expressed as scores according to the Rentrop scoring system. Another 50 cases with normal coronary arteries were selected as control. The levels of HIF-1alpha protein expression in monocyte and lymphocyte in the participants were tested by immunohistochemistry (IHC) and western blot; mRNA levels were measured using reverse transcriptase PCR technique. RESULTS: Compared with the control with normal coronary artery, the patients had higher expression of HIF-1alpha protein tested by IHC and western blot (52.6+/-10.2 vs. 13.7+/-6.2 by IHC, 50.8+/-4.5 vs. 6.5+/-1.8 by western blot); furthermore, significantly higher HIF-1alpha expression was observed in patients with collaterals compared with patients with no collaterals (81.5+/-11.8 vs. 20.7+/-9.4 by IHC; 87.2+/-6.5 vs. 9.5+/-1.4 by western blot). On the transcriptional levels of HIF-1alpha, the result was the same as the protein, there was significant difference of HIF-1alpha between the three groups. The patients with collaterals were the highest (127.3+/-23.9), followed by patients with no collaterals (35.7+/-12.3), and the control were the lowest (23.5+/-9.3). A highly positive correlation was observed between the expression/transcription of HIF-1alpha and collateral score (P<0.01, IHC: r1=0.78, reverse transcriptase PCR: r2=0.69, western blot: r3=0.84). CONCLUSION: These data suggest that higher inductions of HIF-1alpha are associated with coronary collaterals, thus implying that HIF-1alpha may promote coronary collateral formation. Detection of HIF-1alpha expression might be helpful to predict prognosis of patients with coronary artery disease.

Kinetics and thermodynamics of amyloid assembly using a high-performance liquid chromatography-based sedimentation assay.

Nonnative protein aggregation has been classically treated as an amorphous process occurring by colloidal coagulation kinetics and proceeding to an essentially irreversible endpoint often ascribed to a chaotic tangle of unfolded chains. However, some nonnative aggregates, particularly amyloid fibrils, exhibit ordered structures that appear to assemble according to ordered mechanisms. Some of these fibrils, as illustrated here with the Alzheimer's plaque peptide amyloid beta, assemble to an endpoint that is a dynamic equilibrium between monomers and fibrils exhibiting a characteristic equilibrium constant with an associated free energy of formation. Some fibrils, as illustrated here with the polyglutamine repeat sequences associated with Huntington's disease, assemble via highly regular mechanisms exhibiting nucleated growth polymerization kinetics. Here, we describe a series of linked methods for quantitative analysis of such aggregation kinetics and thermodynamics, focusing on a robust high-performance liquid chromatography (HPLC)-based sedimentation assay. An integrated group of protocols is provided for peptide disaggregation, setting up the HPLC sedimentation assay, the preparation of fibril seed stocks and determination of the average functional molecular weight of the fibrils, elongation and nucleation kinetics analysis, and the determination of the critical concentration describing the thermodynamic endpoint of fibril elongation.

Haem oxygenase-1 expression and coronary heart disease--association between levels of haem oxygenase-1 expression and angiographic morphology as well as the quantity of coronary lesions.

OBJECTIVE: The aim of this paper was to investigate the association between levels of HO-1 expression and angiographic morphology as well as the quantity of coronary lesions in patients with coronary heart disease (CHD). METHODS: 110 patients with CHD were diagnosed by coronary angiography which contained coronary lesions in some way. Firstly, the patients were divided into 3 groups according to the angiographic morphology of their coronary lesions: type I (smooth borders) group (n1= 36), type II (irregular borders) group (n2= 48) and type III (long and irregular lesions) group (n3= 26). Secondly, the patients were split into a further 3 groups, named: single-vessel group (SV, 38 cases), double-vessel group (DV, 44 cases) and multi-vessel group (MV, 28 cases) according to the number of coronary lesions. Another 30 patients with normal coronary arteries (diagnosed by coronary angiography) were selected as the control group. The levels of HO-1 protein expression in monocytes and lymphocytes from the subjects were tested by immunohistochemistry and Western blot. A computer picture analysing system was also used to measure the levels of HO-1 protein expression. RESULTS: HO-1 protein was located in cell plasma and the levels of HO-1 protein expression in patients with CHD were significantly higher than in those without CHD (p < 0.01). There were significant differences of HO-1 expression among patients with CHD. Patients with type III lesions had the highest levels, followed by those with type II lesions and the lowest levels were found in patients with type I lesions (p < 0.01). Also, levels of HO-1 protein expression in patients with multi-vessel disease and double-vessel disease were significantly higher than in those with single-vessel disease (p < 0.01). CONCLUSIONS: There is a higher expression of HO-1 in patients with CHD and the levels of HO-1 protein are associated with severity of CHD angiographically.

Germanium in ginseng is low and causes no sodium and water retention or renal toxicity in the diuretic-resistant rats.

Ginseng preparations contain high concentrations of germanium (Ge), which was reported to contribute to diuretic resistance or renal failure. However, Ge content in ginseng and the influence on renal functions remain unclear. Forty rats were randomly divided into control group, low, moderate, and high Ge ginseng-treated group and observed for 25 days. Daily urine, renal functions, and serum and urine electrolytics were measured. Ge retention in the organs and renal histological changes were also evaluated. Ge content ranged from 0.007 to 0.450 µg/g in various ginseng samples. Four groups showed no difference in the daily urine output, glomerular filtration rate, urinary electrolytes excretions, 24 h-urine protein, as well as plasma and urine urea nitrogen, creatinine, osmotic pressure, and pH values. Ge did not cause any renal pathological effects in this study. No Na and water retention was detected in the ginseng-treated groups. Ge retention in various organs was found highest in spleen, followed by the kidney, liver, lung, stomach, heart, and pancreas. The total Ge contents in various ginsengs were low, and ginseng treatment did not affect renal functions or cause renal histological changes.

Serum ubiquitin via CXC chemokine receptor 4 triggered cyclooxygenase-1 ubiquitination possibly involved in the pathogenesis of aspirin resistance.

Extracellular ubiquitin (Ub) with platelet aggregation property was found higher in acute myocardial infarction (AMI) patients. Here we detected the platelet functions and serum Ub levels in 250 AMI patients and 50 healthy volunteers before and after aspirin treatment. The influence of serum Ub on platelet functions was determined in vitro. We found that 47 out of 250 AMI patients showed aspirin resistance (AR) and 203 showed aspirin sensitivity (AS). During hospitalization, AR group had higher serum Ub levels than the AS group or the healthy group, and the serum Ub levels was related to the rates of thrombosis events. The patients with higher serum Ub levels showed that the platelets had more ubiquitinated platelets, higher contents of ubiquitinated proteins and ubiquitinated cyclooxygenase-1 (COX-1). The levels of ubiquitinated COX-1 in the platelets was inversely correlated with acetylated COX-1, the separated ubiquitinated COX-1 activity was approximately twofold or fourfold higher than the total COX-1(ubiquitinated COX-1 and COX-1) or COX-1. In vitro, we found that extracellular Ub, via the CXC chemokine receptor 4 (CXCR4) pathway, facilitated COX-1 to be ubiquitined and prevented aspirin to acetylate its target. Platelets had higher levels of ubiquitinated COX-1 showing poor response to aspirin. Such results were not detected in Ub-free serum or ovalbumin incubated platelets. Serum Ub, via the CXCR4 pathway, facilitated COX-1 to be ubiquitined and activated the platelets possibly involved in the pathogenesis of AR.

Elevated survivin expression in peripheral blood mononuclear cells is central to collateral formation in coronary chronic total occlusion.

Survivin is essential to angiogenesis and revascularization, but its role in coronary collateral formation remains unclear. The role of survivin in peripheral blood mononuclear cells (PBMCs) of coronary chronic total occlusion (CTO) patients was investigated. Coronary CTO patients (n=46; mean age 60.1±8.5, male 54.3%) (CTO group) and normal control patients (n=18; mean age 58.0±10.0, male 55.6%) underwent angiographic collateral vessel grading by Rentrop classification (C0 - C3) and provided peripheral blood between June 2006 and February 2007. Rat hind limb ischemia models were constructed using four equal groups of Sprague-Dawley rats (n=36): normal control, sham operation, operation and granulocyte macrophage colony-stimulating factor (GM-CSF). PBMC numbers and characteristics, collateral vessels, survivin, CD4, CD8, CD44, vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1) expression were determined using RT-PCR, flow cytometry, immunocytochemistry and western blot analysis. PBMC survivin mRNA and protein expression levels were higher in patients with good collateral circulation (C2 + C3) than in patients with no collateral flow (C0) (all P<0.05). Survivin single-positive and survivin and CD8, VEGF and ICAM-1 double-positive percentages were elevated in patients with good collateral circulation compared to those with normal and no collateral flow (all P<0.05), consistent with the rat model results, wherein higher survivin levels produced significantly larger and more visible collateral vessels. In conclusion, elevated survivin expression in PBMCs, particularly survivin and CD8, VEGF, and ICAM-1 double-positive PBMCs, may be crucial for good collateral formation in patients with coronary CTO, as confirmed by assessment of a rat model.

[Clinical study on changes of heme oxygenase-1 expression in patients with acute myocardial infarction].

OBJECTIVE: To investigate changes in heme oxygenase-1(HO-1) in patients with acute myocardial infarction. METHODS: Forty-five patients with acute myocardial infarction and 50 with coronary heart disease (diagnosed by coronary angiography) but without acute myocardial infarction were included in this study, and another 40 patients with normal coronary artery as controls. Levels of HO-1 protein expression in monocyte and lymphocyte isolated from the patients were determined by immunohistochemistry and Western blot. Computer picture analyzing system was also used to measure levels of HO-1 protein expression. RESULTS: HO-1 protein expression was located in the cytoplasm. The levels of HO-1 protein expression in patients with acute myocardial infarction were significantly higher than those without acute myocardial infarction (P<0.01). In addition, low levels of HO-1 protein expression were observed in patients with normal coronary artery. CONCLUSION: There is a higher expression of HO-1 in patients with acute myocardial infarction, and a lower expression in patients with normal coronary artery.