CTRP9 Promotes Brown Adipose Tissue Lipolysis in Mice Fed a High-Fat Diet.

BACKGROUND: This study aimed to elucidate the molecular mechanism through which C1q/tumor necrosis factor (TNF)-related protein 9 (CTRP9) acts in the formation and differentiation of brown adipose tissue (BAT). METHODS: Adenovirus particles encoding CTRP9 and green fluorescent protein were inoculated into the scapula of C57BL/6J mice and fed a high-fat diet for 8 weeks; the body weight, lipid droplet morphology, glucose tolerance, insulin tolerance, and protein expression levels were analyzed. In addition, CTRP9 adenovirus was transfected into brown preadipocytes, and differentiation was induced to identify the effect of CTRP9 overexpression on adipocyte differentiation. RESULTS: CTRP9 overexpression significantly increased the weight gain of mice. Additionally, the CTRP9 overexpression group exhibited significantly increased adipose tissue weight and glucose clearance rates and decreased insulin sensitivity and serum triglyceride levels compared to the control group. Furthermore, CTRP9 overexpression significantly upregulated the adipose triglyceride lipase (ATGL) and perilipin 1 protein expression levels in BAT. The cell experiment results confirmed that CTRP9 overexpression significantly inhibited the adipogenesis of brown adipocytes as evidenced by the downregulation of uncoupling protein 1, beta-3 adrenergic receptor, ATGL, and hormone-sensitive lipase mRNA levels and the significant suppression of uncoupling protein 1, ATGL, and perilipin 1 protein levels in brown adipocytes. CONCLUSIONS: The finding of this study demonstrated that CTRP9 promotes lipolysis by upregulating ATGL expression in vivo and inhibits the differentiation of brown preadipocytes in vitro.

The safety and feasibility of mini-invasive Bentall surgery via right anterior mini-thoracotomy.

Background: The right anterior mini-thoracotomy (RAMT) approach has become a popular technique in cardiac surgery and applied in valve surgery. However, there is very limited evidence on the application of RAMT in the Bentall surgery. In the present study, we aimed to evaluate the safety and feasibility of the RAMT approach in Bentall surgery. Methods: A retrospective analysis was performed on 27 patients who underwent Bentall surgery between September 2020 and April 2022 in the First Affiliated Hospital of Xi'an Jiaotong University. Follow-ups were undertaken 1 and 6 months after their operations. The baseline, perioperative, and follow-up results were retrospectively analyzed. Results: A total of 27 male patients aged 48-61 years were included in the study. The operation time ranged from 4.0 to 5.0 hours, with a median of 4.5 hours. The median aortic cross-clamping time was 122 minutes [interquartile range (IQR): 109-145 minutes], and the median cardiopulmonary bypass (CPB) time was 156 minutes (IQR: 143-183 minutes). The median intensive care unit stay was 3 days (IQR: 1.75-4.25 days). The ventilation time ranged from 6.5 to 22.0 hours, with a median of 13.0 hours. The median drainage volume in the first 24 hours was 210 mL. In the following-up data, no deaths or severe complications were observed. Conclusions: The mini-Bentall procedure through an RAMT approach is a feasible and safe approach with few wounds and good clinical results in patients undergoing aortic root replacement.

Relationship between the postoperative lactate dynamic levels, the acute gastrointestinal injury and the prognosis among patients who undergo surgical treatment for acute type A aortic dissection.

Introduction: This study aimed to determine the relationship between the postoperative lactate dynamic levels, the postoperative acute gastrointestinal injury (AGI), and the prognosis among the patients who underwent surgical treatment for an acute Stanford type-A aortic dissection (aTAAD). Methods: A total of 271 aTAAD patients were recruited and monitored. Of the 271 aTAAD patients, 29.2% developed an AGI and were designated as the AGI group (n = 79); the other patients (n = 192) were designated as the non-AGI group. According to the 2-year follow up, the aTAAD patients were also divided into the alive and death subgroups for further analysis. Results: Binary logistic regression analysis revealed that the postoperative 4-h lactate (P4L) level, time-to-return to the normal blood lactate level (TRNL), postoperative 16-h lactate (P16L) level, and neutrophil granulocyte (NEU) count had a good predictive value for an AGI after aTAAD. The 8-week and 2-year mortality rates were higher in the AGI group than the non-AGI group (P < 0.05). Basic data and clinical characteristics were significantly different between the alive and death groups (P < 0.05). A higher AGI rate and mortality occurred in the P4L level ≥10.15 mmol/L subgroup, TRNL ≥21-h subgroup, P16L level ≥2.95 mmol/L subgroup, NEU count ≥10.9 × 109/L subgroup, PaO2 < 77.7 mmHg subgroup, WBC count ≥9.58 × 109/L subgroup, and the operative time ≥427 min subgroup than the corresponding comparison subgroups (P < 0.05). The postoperative 0-h lactate (P0L) level, TRNL, postoperative 24-h lactate (P24L) level, D-dimer level, fibrinogen degradation products (FDP) level, duration of mechanical ventilation, and length of hospitalization were independent factors influencing the 30-day mortality rate in patients who underwent surgery for an aTAAD (P < 0.05). Cox regression multivariate analysis after univariate analysis of all-cause mortality showed the TRNL, postoperative 12-h lactate (P12L) level, P16L level, P24L level, D-dimer level, FDP level, and length of hospitalization were independently associated with the 2-year mortality rate in patients who underwent surgery for an aTAAD (P < 0.05). Conclusion: The postoperative lactate changes and TRNL effectively predicted postoperative AGI and the mortality rate in patients with who underwent surgery for an aTAAD. The TRNL and P24L level were independent risk factors for the 30-day and 2-year mortality rates in patients who underwent surgery for an aTAAD.

SFRP4 Reduces Atherosclerosis Plaque Formation in ApoE Deficient Mice.

Secreted frizzled related protein 4 (SFRP4), a member of the SFRPs family, contributes to a significant function in metabolic and cardiovascular diseases. However, there is not enough evidence to prove the antiatherosclerosis effect of SFRP4 in ApoE knock-out (KO) mice. ApoE KO mice were fed a western diet and injected adenovirus (Ad)-SFRP4 through the tail vein for 12 weeks. Contrasted with the control cohort, the area of atherosclerotic plaque in ApoE KO mice overexpressing SFRP4 was reduced significantly. Plasma high-density lipoprotein cholesterol was elevated in the Ad-SFRP4 group. RNA sequence analysis indicated that there were 96 differentially expressed genes enriched in 10 signaling pathways in the mRNA profile of aortic atherosclerosis lesions. The analysis data also revealed the expression of a number of genes linked to metabolism, organism system, and human disease. In summary, our data demonstrates that SFRP4 could play an important role in improving atherosclerotic plaque formation in the aorta.

The Preoperative Uric Acid-to-Albumin Ratio as a New Indicator to Predict Long-Term Prognosis After Surgery for Patients with Acute Type A Aortic Dissection.

BACKGROUND: The long-term prognosis of patients with acute type A aortic dissection (AAD) is poor, despite emergency surgical treatment. Therefore, it is imperative to evaluate patient risk factors to improve the prognosis. The aim of this study was to analyze the ability of the uric acid-to-albumin ratio (UAR) to predict the long-term mortality of patients with type A AAD after surgery. METHODS AND RESULTS: A total of 289 patients with type A AAD who had received surgical treatment was enrolled in this study. Peripheral blood samples were collected before anesthesia induction. All patients were divided into the UAR < 9.875 group and the UAR ≥ 9.875 group, and mortality significantly differed between the two groups. The patients were further divided into survival and non-survival groups, according to whether death occurred after the procedure based on a one-year follow up. Factors, including age, hypertension, albumin, UAR, and D-dimer, differed significantly between the survival and non-survival groups. The independent risk factors for long-term death in patients with type A AAD were analyzed by univariable and multivariable COX regression analyses, and the predictive value of these indices for postoperative mortality was assessed based on the receiver operating characteristic (ROC) curves. Preoperative UAR (HR 1.904, 95% CI, 1.097 to 3.305; P < 0.05), D-dimer (HR, 1.991,95% CI, 1.116 to 3.554; P < 0.05 ), and age (HR 2.216, 95% CI, 1.287 to 3.815; P < 0.05) were identified as independent risk factors for one-year mortality in patients with Type A AAD. The area under the ROC curve (AUC) of UAR was 0.618 [95% (0.544, 0.693)], and the sensitivity and specificity were 69.6% and 51.8%, respectively (P = 0.003). The AUC for albumin was 0.349 [95% (0.274, 0.425)], and the sensitivity and specificity were 26.1% and 51.8%, respectively (P = 0.000), The AUC for uric acid was 0.544 [95% (0.470, 0.619)], and the sensitivity and specificity were 78.3% and 34.5%, respectively (P = 0.265). The AUC for UAR + age + D-dimer was 0.751 [95% (0.681, 0.821)], and the sensitivity and specificity were 76.8% and 68.2%, respectively. CONCLUSIONS: UAR in patients with type A AAD may be used as a new independent risk factor for long-term mortality. Its predictive value is superior to that of albumin or uric acid alone. The combination of UAR, age, and D-dimer provide good prognostic value.

[Corrigendum] Thymoquinone inhibits epithelial­mesenchymal transition in prostate cancer cells by negatively regulating the TGF­ß/Smad2/3 signaling pathway.

After the publication of the article, an interested reader drew to the authors' attention that the Du145 'Control' migration panel in Fig. 2C appeared to overlap with the Du145 'Control' invasion panel in Fig. 5A; furthermore, two of the Du145 panels in Fig. 5A also appeared to overlap. The authors have consulted their original data, and realize that these figures were inadvertently assembled incorrectly. The corrected versions of Figs. 2 and 5, incorporating the correct data for the Du145 'Control' panel in Fig. 2C, and the TQ­/TGF­ß OE­ invasion and migration panels, and the TQ+/TGF­ß OE+ migration panel, in Fig. 5A, are shown on the next page. These further corrections do not grossly affect the results or the conclusions reported in this work. The authors all agree to this Corrigendum, and are grateful to the Editor of Oncology Reports for granting them the opportunity to correct the errors that were made during the assembly of these figures. Lastly, the authors apologize to the readership for any inconvenience these errors may have caused. [Oncology Reports 38: 3592­3598, 2017; DOI: 10.3892/or.2017.6012].

Clinical characteristics and risk factors of in-hospital gastrointestinal bleeding in patients with acute myocardial infarction.

Background: Gastrointestinal bleeding (GIB) is one of the most serious complications of acute myocardial infarction (AMI) and is correlated with poor outcomes. Objective: To evaluate the prevalence, risk factors and in-hospital mortality of GIB in patients with AMI. Methods: This observational case-control study retrospectively enrolled consecutive patients with AMI from the Department of Cardiovascular Medicine and Cardiovascular Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2020. GIB after AMI was identified by International Classification of Diseases (ICD) codes from inpatient medical settings and validated by medical record review. AMI patients without GIB were accordingly classified as the control group. Propensity score matching (PSM) was used to match with the GIB group and the control group. All anonymized clinical data were provided by the Biobank of the First Affiliated Hospital of Xi'an Jiaotong University. Results: A total of 5,868 AMI patients were enrolled, 0.87% (51/5,868) of whom developed GIB after AMI. On the univariate analysis, history of diabetes, chronic kidney disease, Killip IV, a lower hemoglobin concentration, a higher serum level of creatinine, blood urea nitrogen and D-dimer were closely associated with the risk of GIB (P < 0.05). On the multivariable analysis, a lower hemoglobin concentration (OR: 0.93, 95% CI: 0.89-0.96, P < 0.001) was independently associated with the risk of GIB. Patients with GIB had a much higher in-hospital mortality rate than those without GIB (14.3 vs. 2.1%, P = 0.047). In-hospital mortality among patients with GIB after AMI appeared to be associated with a decreased hemoglobin concentration (OR: 0.93, 95% CI: 0.86-0.99, P = 0.045) and Killip IV (OR: 51.59, 95% CI: 2.65-1,005.30, P = 0.009). Conclusion: The history of diabetes, poor renal function and heart failure were associated with the high risk of GIB in patients experiencing AMI. The in-hospital mortality in patients with AMI complicating GIB was higher than that in patients without GIB and was associated with a decreased hemoglobin concentration and high Killip classification.

C1QL1/CTRP14 Is Largely Dispensable for Atherosclerosis Formation in Apolipoprotein-E-Deficient Mice.

The purpose of this study was to investigate the influence of C1QL1 on atherosclerosis as well as the transcriptomic alteration of the aorta. While complement C1ql-like 1 (C1QL1) is one of the C1q/tumor-necrosis-factor-related protein (CTRP) family members, also known as CTRP14, and is synthesized and secreted mainly by the brain and adipose tissues, the functional properties of the C1QL1/CTRP14 protein outside the brain and adipocytes remain, however, unknown. In this regard, apolipoprotein E (ApoE) knockout (KO) mice were fed a Western diet and injected with adenovirus (Ad) green fluorescent protein or Ad-C1QL1 through the tail vein for 12 weeks. In contrast with the control cohort, the area of atherosclerotic plaque in ApoE KO mice overexpressing C1QL1 showed no significant difference, and the RNA sequence revealed that there were only 111 differentially expressed genes (DEGs) enriched in 26 signaling pathways of the mRNA profile in the aortic atherosclerosis lesions. This analysis also revealed the expression of several genes related to metabolism, organismal system, and human diseases such as type II diabetes, which are not associated with the formation of atherosclerosis in the aorta. These findings illustrate that C1QL1 is largely dispensable for atherosclerosis formation in ApoE-deficient mice and does not improve atherosclerotic plaque formation in the aorta.

Atrial Cardiomyopathy Predicts Worse Outcome in Patients With Lung Cancer.

Background: Reports of the clinical outcomes associated with the co-occurrence of atrial cardiomyopathy (ACM) and lung cancer (LC) are limited. Objectives: This study aims to investigate the influence of ACM on the prognosis of LC patients and related clinical determinants. Methods: Newly diagnosed LC patients from January 1st, 2015, to December 31st, 2020, were retrospectively enrolled at the First Affiliated Hospital of Xi'an Jiaotong University. The demographics and overall survival (OS) of the patients with or without ACM were compared. The survival rate was analyzed using the Kaplan-Meier method and multivariate Cox regression analysis. Binary logistic regression analysis was used to determine the risk factors for ACM. Results: A total of 306 patients (65.04 ± 10.30 years of age, 72.88% male) were analyzed. The prevalence of ACM in the non-small cell lung cancer (241, 78.76%) and small cell lung cancer (65, 21.24%) population was not statistically different. Overall, 53 (17.32%) LC patients had coexisting ACM. ACM patients were older (69 vs. 64, p = 0.0013) and had higher D-dimer levels (1.0 vs. 0.6, p = 0.001), lower serum calcium levels (2.23 vs. 2.31, p = 0.001), lower left ventricular ejection fraction (LVEF) values (67% vs. 69%, p = 0.036) and had more frequent coronary comorbidity disease (16.98% vs. 8.82%, p = 0.031). The median OS for patients with or without ACM was 15 months and 25 months, respectively (p = 0.018). Coexisting ACM compared to non-ACM was associated with worse OS in patients with LC (HR = 1.543, 95% CI: 1.042-2.283, p = 0.030). Conclusion: Coexisting ACM is associated with undesirable survival outcomes in patients with LC. These findings could help us to better understand the cardiac burden in these patients and provide additional risk stratification for them.

C1q/Tumor Necrosis Factor-Related Protein 9: Basics and Therapeutic Potentials.

C1q/tumor necrosis factor-related protein 9 (CTRP9) is a newly discovered adipokine that is the closest paralog of adiponectin. Proteolytic cleavage of CTRP9 leads to the release of the globular domain (gCTRP9), which serves as the major circulating subtype. After binding with adiponectin receptor 1 (AdipoR1) and N-cadherin, CTRP9 activates various signaling pathways to regulate glucose and lipid metabolism, vasodilation and cell differentiation. Throughout human development and adult life, CTRP9 controls many biological phenomena. simultaneously, abnormal gene or protein expression of CTRP9 is accompanied by a wide range of human pathological phenomena. In this review, we briefly introduce CTRP9 and its associated signaling pathways and physiological functions, which may be helpful in the understanding of the occurrence of diseases. Moreover, we summarize the broader research prospects of CTRP9 and advances in therapeutic intervention. In recent years, CTRP9 has attracted extensive attention due to its role in the pathogenesis of various diseases, providing further avenues for its exploitation as a potential biomarker or therapeutic target.

Scalable total synthesis of (+)-aniduquinolone A and its acid-catalyzed rearrangement to aflaquinolones.

The strong antibacterial, antiviral and anticancer activities demonstrated by quinolones make them promising lead structures and important synthetic targets for drug discovery. Here, we report, to the best of our knowledge, the first scalable total synthesis of antiviral (+)-aniduquinolone A, possessing a 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one skeleton. This synthetic strategy explores E-stereoselective Horner-Wadsworth-Emmons (HWE) olefination as the key step to assemble isopropenyl substituted tetrahydrofuran onto the 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one core, which is built by highly diastereoselective intramolecular aldol reaction. Moreover, two sets of stereoisomers of aniduquinolone A with substantially overlapping NMR data were synthesized completely and assigned unambiguously by comprehensive analysis of both their spectroscopic and X-ray diffraction data. Unexpectedly, aflaquinolones A, C, and D that feature different 2,4-dimethyl cyclohexanone moieties were transformed successfully from (+)-aniduquinolone A by treating with TFA. The methodology delineated herein can be applied broadly to the synthesis of natural alkaloids containing the core structure of 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one.

Comparison of Clinical Outcomes of Different Connection Modes of Extracorporeal Membrane Oxygenation Combine with Continuous Renal Replacement Therapy.

OBJECTIVE: To evaluate the effect of different connection modes of ECMO and CRRT on patients with acute kidney injury (AKI). METHODS: Twenty-one patients received ECMO with AKI. These patients were admitted to our center from December 2018 to February 2021, selected, and treated with both ECMO and CRRT. They were divided into A connection mode (pre-membrane-pre-pump connection) and B connection mode (post-membrane-post-pump connection). We compared clinical indicators and outcomes between two connection modes. RESULTS: There were eight cases (38.91%) in A connection mode and 13 cases (61.09%) in B connection mode, with median durations of ECMO assistance of 5 days and 7 days, respectively. Median flow rates of ECMO of 3.0 L/min and 2.5 L/min, respectively; CRRT flow rates of 200 mL/min and 180 mL/min, respectively. CRRT filter lifetime was over 48h in both connection modes. Except for NT-pro BNP, no significant differences in clinical indicators were observed between the two groups before or after the treatment (P > .05). CONCLUSION: Both connection modes could achieve the therapeutic purpose and need no higher level of anticoagulation for patients simultaneously treated with ECMO and CRRT. Two modes had no impact on treatment effect and clinical indicators in patients. It had no effect on length of ICU stay and prognostic.

Right ventricular haemangioma as a rare cause of chest pain: a case report.

BACKGROUND: Cardiac haemangioma is a rare primary cardiac tumour. Most patients with cardiac haemangioma have no typical symptoms, and some may present with non-specific manifestations, such as shortness of breath, heart palpitations, or cardiac insufficiency, making it difficult to distinguish cardiac haemangioma from other diseases. We report a case of cardiac haemangioma that present with chest pain. This haemangioma was finally completely excised to relieve the patient's symptoms and a avoid poor prognosis. CASE SUMMARY: A 14-year-old boy presented with an intermittent and progressive non-exertional chest pain for 2 weeks. Echocardiography showed a space-occupying mass at the right ventricular apex, which was later confirmed by computed tomography angiography and magnetic resonance imaging (MRI). The mass was successfully resected, and postoperative pathology confirmed a cardiac cavernous haemangioma. The patient had an uneventful postoperative recovery at the 8-month follow-up. DISCUSSION: Cardiac haemangioma is a benign tumour with no typical clinical manifestations, and very few patients may present with chest pain. Preoperative echocardiography, computed tomography, and MRI are helpful for diagnosis, and surgery can relieve symptoms and may improve the prognosis of patients with cardiac haemangioma.

Autophagy induction enhances tetrandrine-induced apoptosis via the AMPK/mTOR pathway in human bladder cancer cells.

Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the roots of Stephania tetrandra is a traditional Chinese medicine and exerts anticancer capacity in various types of cancers. Previous studies have shown that tetrandrine induces apoptosis in bladder cancer cells via activation of the caspase cascade. However, the underlying mechanism has not yet been reported. Autophagy is a cellular process involved in the degradation of broken proteins and aging organelles to maintain homeostasis. Recent studies indicate that autophagy is implicated in cancer therapy. Thus, we focused on the correlation between autophagy and apoptosis upon tetrandrine treatment in human bladder cancer cells. Firstly, our results observed a marked increase in autophagic double-membrane vacuoles and fluorescent puncta of red fluorescence protein-green fluorescence protein-LC3 (GRP-RFP-LC3) upon tetrandrine treatment, as evidenced by transmission electron microscopy and confocal fluorescence microscopy. Secondly, the expression of LC3-II was increased in tetrandrine-treated T24 and 5637 cells in a time- and concentration-dependent manner. Subsequently, downregulation of p62 and LC3 turnover assay further confirmed that tetrandrine induced autophagic flux in bladder cancer T24 and 5637 cells. Thirdly, the protein levels of phosphorylated-AMP-activated protein kinase (AMPK) and phosphorylated-acetyl-coenzyme A carboxylase (ACC) were upregulated in the tetrandrine-treated cells, while the mammalian target of rapamycin (mTOR)-related proteins were downregulated. Moreover, AICAR, a common AMPK activator, further increased the expression the LC3-II, while AMPK inhibitor compound C partially reversed the LC3-II protein levels in bladder cancer T24 cells. Finally, AICAR significantly reinforced the growth inhibition and apoptosis induction of tetrandrine in T24 and 5637 cells, while compound C had an opposite effect, suggesting that AMPK-mediated autophagy enhanced the cytotoxic and pro-apoptosis effect of tetrandrine in human bladder cancer cells. Taken together, the present study showed that tetrandrine induced autophagy in human bladder cancer cells by regulating the AMPK/mTOR signaling pathway, which contributed to the apoptosis induction by tetrandrine, indicating that tetrandrine may be a potential anticancer candidate for the treatment of bladder cancer, and autophagy may be a possible mechanism for cancer therapy.

Thymoquinone inhibits epithelial-mesenchymal transition in prostate cancer cells by negatively regulating the TGF-ß/Smad2/3 signaling pathway.

Thymoquinone, a major ingredient of black seed oil (Nigella sativa), has been shown to exhibit anticancer capacity in various types of cancers. However, there are few studies concerning the correlation between thymoquinone and epithelial-to-mesenchymal transition (EMT) in prostate cancer. In the present study, we firstly found that thymoquinone showed antimetastatic capacity in prostate cancer DU145 and PC3 cells. Additionally, thymoquinone reversed EMT by increasing E-cadherin expression and decreasing vimentin and Slug expression in a concentration-dependent manner. Recent studies have shown that the transforming growth factor-ß (TGF-ß) signaling pathway may be associated with EMT. Intriguingly, the expression of TGF-ß, Smad2 and Smad3 at the mRNA and protein levels was notably reduced upon thymoquinone treatment in prostate cancer DU145 and PC3 cells. Subsequently, we confirmed that thymoquinone repressed metastasis and EMT of prostate cancer through downregulation of the TGF-ß/Smad2/3 signaling pathway, which may be partially reversed by TGF-ß overexpression. In summary, our findings demonstrated that thymoquinone suppressed the metastatic phenotype and reversed EMT of prostate cancer cells by negatively regulating the TGF-ß/Smad2/3 signaling pathway. These findings suggest that thymoquinone is a potential therapeutic agent against prostate cancer which functions by targeting TGF-ß.

Methylene blue modulates transendothelial migration of peripheral blood cells.

Vasoplegia is a severe complication after cardiac surgery. Within the last years the administration of nitric oxide synthase inhibitor methylene blue (MB) became a new therapeutic strategy. Our aim was to investigate the role of MB on transendothelial migration of circulating blood cells, the potential role of cyclic cGMP, eNOS and iNOS in this process, and the influence of MB on endothelial cell apoptosis. Human vascular endothelial cells (HuMEC-1) were treated for 30 minutes or 2 hours with different concentrations of MB. Inflammation was mimicked by LPS stimulation prior and after MB. Transmigration of PBMCs and T-Lymphocytes through the treated endothelial cells was investigated. The influence of MB upon the different subsets of PBMCs (Granulocytes, T- and B-Lymphocytes, and Monocytes) was assessed after transmigration by means of flow-cytometry. The effect of MB on cell apoptosis was evaluated using Annexin-V and Propidium Iodide stainings. Analyses of the expression of cyclic cGMP, eNOS and iNOS were performed by means of RT-PCR and Western Blot. Results were analyzed using unpaired Students T-test. Analysis of endothelial cell apoptosis by MB indicated a dose-dependent increase of apoptotic cells. We observed time- and dose-dependent effects of MB on transendothelial migration of PBMCs. The prophylactic administration of MB led to an increase of transendothelial migration of PBMCs but not Jurkat cells. Furthermore, HuMEC-1 secretion of cGMP correlated with iNOS expression after MB administration but not with eNOS expression. Expression of these molecules was reduced after MB administration at protein level. This study clearly reveals that endothelial response to MB is dose- and especially time-dependent. MB shows different effects on circulating blood cell-subtypes, and modifies the release patterns of eNOS, iNOS, and cGMP. The transendothelial migration is modulated after treatment with MB. Furthermore, MB provokes apoptosis of endothelial cells in a dose/time-dependent manner.

Selenium and cardiovascular surgery: an overview.

Selenium is an essential nutritional element to mammalians necessary for the active function of different oxidant enzymes, as glutathione peroxidase (GPx), thioredoxin reductases (TrxR), and iodothyronine deiodinases (IDD). The anti-oxidative effect of selenium is pivotal for the human physiology. Oxidative stress is associated with various diseases, such as cardiovascular disease, diabetes mellitus or cancer, and is also associated with the majority of surgical procedures. Particularly, the use of cardiopulmonary bypass for open cardiac surgery with aortic clamping is always related to oxidative stress due to ischemia and reperfusion. Whereas myocardial protection with different temperatures and cardioplegic solutions has become more efficient, reperfusion is often followed by the activation of an injurious oxidative cascade. The pathogenesis of ischemia/reperfusion injury depends on many factors, among them, reactive nitrogen species (RNS) and reactive oxygen species (ROS) are considered as initiators of the injury. ROS formed during oxidative stress can initiate lipid peroxidation, oxidize proteins to inactive states and cause DNA strand breaks. ROS production is physiologically controlled by free radical scavengers such as GPx and TrxR, and superoxide dismutase systems. GPx and TrxR are seleno-cysteine dependent enzymes, and their activity is known to be related to selenium availability. Furthermore, selenium has been reported to regulate gene expression of these selenoproteins as a cofactor and there is some evidence that selenium supplementation can attenuate the oxidative stress and decrease the complications after cardiac surgery. However, other clinical studies failed to demonstrate an association between selenium deficiency and cardiovascular outcomes. The aim of our review is to summarize the experimental and clinical evidence of preoperative selenium supplementation and therapy after cardiac surgery, focusing on the pathophysiology of oxidative stress and the clinical usage of selenium.

Multimodality FDG PET/CT appearance of pulmonary tuberculoma mimicking lung cancer and pathologic correlation in a tuberculosis-endemic country.

OBJECTIVES: Differentiation between pulmonary tuberculoma and malignancy by preoperative diagnostic imaging sometimes proves difficult. The purpose of this study is to investigate variable manifestations of pulmonary tuberculoma mimicking lung cancer on fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) image and pathologic correlation. PATIENTS AND METHODS: Twenty-five patients with a high suspicion of malignancy and histopathologically diagnosed as pulmonary tuberculoma were included. Their FDG PET/CT images, clinical data, and pathologic findings were investigated. RESULTS: There were 18 men and seven women. The mean age was 52 ± 8.8 years. The maximal diameter of pulmonary tuberculoma ranged from 1.7 to 4.2 cm. CT scan revealed that abnormal signs associated with malignancy such as spicular radiation, notching, and pleural indentation also frequently manifested in tuberculoma. During early imaging, positive FDG uptake was identified in 21 patients (84%), intermediate uptake in 3 patients (12%) and negative uptake in 1 patient (4%). During delayed imaging, 16 patients (64%) showed persistent elevated FDG accumulation and 8 patients (32%) experienced a slight drop of FDG accumulation. Pathologically active tuberculoma showed significantly higher FDG radioactivity during both early and delayed imaging than inactive lesion (P < 0.05). Lymphadenopathy with positive FDG uptake was identified in nine patients (36%). CONCLUSION: Pulmonary tuberculomas mimicking lung cancer, most of which were pathologically active lesions, commonly displayed abnormal appearances in CT scan and an increase in FDG uptake, similar to changes seen on malignancy. Coexistent lymphadenopathy made differential diagnosis even more complicated. These results suggested that positive FDG PET/CT findings should be interpreted with caution in tuberculosis-endemic regions.