Liewen Pang

Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR-γ/LXR-α signaling pathway

Cholesterol efflux from macrophages is a critical mechanism to prevent the development of atherosclerosis. Here, we sought to investigate the effects of arctigenin, a bioactive component of Arctium lappa, on the cholesterol efflux in oxidized low-density lipoprotein (oxLDL)-loaded THP-1 macrophages. Our data showed that arctigenin significantly accelerated apolipoprotein A-I- and high-density lipoprotein-induced cholesterol efflux in both dose- and time-dependent manners. Moreover, arctigenin treatment enhanced the expression of ATP binding cassette transporter A1 (ABCA1), ABCG1, and apoE, all of which are key molecules in the initial step of cholesterol efflux, at both mRNA and protein levels. Arctigenin also caused a concentration-dependent elevation in the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α). The arctigenin-mediated induction of ABCA1, ABCG1, and apoE was abolished by specific inhibition of PPAR-γ or LXR-α using small interfering RNA technology. Our results collectively indicate that arctigenin promotes cholesterol efflux in oxLDL-loaded THP-1 macrophages through upregulation of ABCA1, ABCG1 and apoE, which is dependent on the enhanced expression of PPAR-γ and LXR-α.

Low Pretherapeutic Serum Albumin as a Risk Factor for Poor Outcome in Esophageal Squamous Cell Carcinomas

The number of esophageal cancer patients is increasing worldwide and lots of patients suffer from malnutrition and hypoalbuminemic. Serum albumin is a widely acceptable method of assessing nutritional and inflammation status in cancer patients. But whether serum albumin has prognostic value with regard to short-term and long-term outcomes in patients who undergo esophagectomy for cancer is still unclear. We therefore investigated the prognostic role of serum albumin in patients with esophageal cancer. We retrospectively reviewed 208 patients who underwent esophagectomy from September 1, 2003 to December 31, 2008. Clinico-pathological characteristics and postoperative outcomes were compared between different pretherapeutic serum albumin classes: low (hypoalbuminemic), <35 g/l; middle, 35–40 g/l and high, >40 g/l. Older, female, and higher T-stages were more likely to be associated with hypoalbuminemic. Meanwhile, hypoalbuminemic patients had a higher rate of postoperative mortality and complications including sepsis, respiratory insufficiency, arrhythmia, and cardiac insufficiency. But for preoperative comorbidities, no significant difference was found between different pretherapeutic serum albumin classes. The overall 5-year survival rate was 28.6%, 43.9%, and 50.8% for patients with low, middle, and high pretherapeutic serum albumin levels, respectively. Hypoalbuminemic was associated with poor survival (P = 0.016). In a multivariate analysis, the pretherapeutic albumin level was proved to be an independent predictor of survival (hazard ratio = 0.731; 95% confidence interval: 0.544–0.982, P = 0.037). Pretherapeutic serum albumin level is a significant prognostic factor for short-term and long-term outcomes in patients who undergo esophagectomy for cancer, which therefore should be taken into consideration along with other well-defined prognostic factors for better preoperative assessment and prognostic evaluation.

Preoperative Insertion of an Intra-Aortic Balloon Pump Improved the Prognosis of High-Risk Patients Undergoing Off-Pump Coronary Artery Bypass Grafting

This study investigated the efficacy and safety of preoperative insertion of an intra-aortic balloon pump (IABP) in high-risk coronary atherosclerotic disease patients undergoing off-pump coronary artery bypass grafting (OPCAB). A total of 232 patients were recruited to the study, of whom 107 underwent percutaneous insertion of an IABP prior to OPCAB. The remaining 125 patients underwent OPCAB alone. Pre-, peri- and postoperative parameters were compared between the two groups. Preoperative insertion of an IABP was associated with a shorter stay in intensive care, decreased incidence of postoperative dialysis and acute heart failure, and a reduction in postoperative mortality compared with OPCAB alone. There were no between-group differences in terms of haematocrit level, number of distal anastomoses, volume of postoperative drainage or incidence of reoperation for bleeding and postoperative stroke/cerebrovascular accident. In conclusion, preoperative insertion of an IABP improved the prognosis of high-risk CAD patients undergoing OPCAB.

The Gene Polymorphism of LOX1 Predicts the Incidence of LVH in Patients with Essential Hypertension

Background: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been shown to play an important role in cardiac remodeling under different pathologic conditions. The role of genetic polymorphisms in the LOX1 gene, however, remains unclear in the development of left ventricular hypertrophy (LVH) for patients with hypertension. Methods: A total of 536 patients diagnosed with essential hypertension (EH) were recruited in this study. Patients were assigned to the LVH+ (n=143) and LVH- (n=393) groups, respectively. The serum LOX1 level was measured and three single nucleotide polymorphisms (SNPs), i.e. intron 4 (G→A), intron 5(T→G), and 3′ UTR (T→C) of the LOX1 gene were genotyped. Results: The genotype frequencies of intron 4 G>A and 3′UTR T>C were not significantly different between the LVH+ and LVH- groups (both P>0.05), however, frequencies of 501G>C were significantly different between those two groups (P=0.007). The 501CC genotype carriers had a markedly higher serum LOX1 level and an increased risk to develop LVH (adjusted OR=2.444, adjusted P=0.002). There was a positive correlation between serum LOX1 level and left ventricular mass index (r=0.907, P<0.001); a cutoff value of 1.0 ng/mL for sLOX-1 was applied to significantly differentiate the LVH+ patients from the LVH- patients with 84% sensitivity and 86% specificity. Conclusion: Our data suggest that both the 501>C SNP in the LOX1 gene and the serum LOX1 level may be used to predict the development of LVH among EH patients.

A Long-Term and Slow-Releasing Hydrogen Sulfide Donor Protects against Myocardial Ischemia/Reperfusion Injury

Hydrogen sulfide (H2S) has been recognized as an important gasotransmitter exerting various physiological effects, especially in the cardiovascular system. Herein we investigated the cardioprotective effects of a novel long-term and slow-releasing H2S donor, DATS-MSN, using in vivo myocardial ischemia/reperfusion (I/R) models and in vitro hypoxia/reoxygenation cardiomyocyte models. Unlike the instant-releasing pattern of sodium hydrosulphide (NaHS), the release of H2S from DATS-MSN was quite slow and continuous both in the cell culture medium and in rat plasma (elevated H2S concentrations during 24 h and 72 h reperfusion). Correspondingly, DATS-MSN demonstrated superior cardioprotective effects over NaHS in I/R models, which were associated with greater survival rates, reduced CK-MB and troponin I levels, decreased cardiomyocyte apoptosis index, increased antioxidant enzyme activities, inhibited myocardial inflammation, greater reduction in the infarct area and preserved cardiac ejection fraction. Some of these effects of DATS-MSN were also found to be superior to classic slow-releasing H2S donor, GYY4137. In in vitro experiments, cardiomyocytes injury was also found to be relived with the use of DATS-MSN compared to NaHS after the hypoxia/reoxygenation processes. The present work provides a novel long-term and slow-releasing H2S donor and an insight into how the release patterns of H2S donors affect its physiological functionality.

HIF2α induces cardiomyogenesis via Wnt/β-catenin signaling in mouse embryonic stem cells

BackgroundEmbryonic stem cells (ESCs) are pluripotent stem cells and can differentiate into cardiomyocytes when cultured in appropriate conditions. The function of hypoxia-inducible factors (HIFs) has been identified in directing the formation of cardiac lineages. The purpose of this study was to investigate the ability of HIF2α to induce differentiation of ESCs into cardiomyocytes and to explore the potential underlying molecular mechanisms.MethodsCardiac differentiation from mouse ESCs was analyzed using the “hanging drop” method, and success was determined by assaying the numbers of beating embryoid bodies and the expression level of cardiac markers. The expression of HIF2α was then manipulated during cardiac differentiation with piggyBac transposon and the lentivirus system. The underlying mechanism was finally examined via administering selective inhibitors of the Wnt/β-catenin signaling pathway.ResultsOverexpressing HIF2α can significantly drive mouse ESCs to form cardiomyocytes. Contrarily, knockdown of HIF2α inhibits the emergence of cardiac cells. In addition, the cardiomyogenesis-promoting effect of HIF2α occurred by increasing the protein level of β-catenin, an effector that contributes to cardiac differentiation at an early stage of ESC differentiation.ConclusionHIF2α has a cardiomyogenesis-promoting effect in ESCs via enhancing the activation of the Wnt/β-catenin signaling pathway. Our results may be beneficial for generating and applying cardiomyocytes from ESCs safely and effectively in the future.

The Expression and Prognostic Impact of the PI3K/AKT/mTOR Signaling Pathway in Advanced Esophageal Squamous Cell Carcinoma:

The abnormal phosphatase and tensin homolog expression and activated phosphoinositide-3 kinase/Protein kinase B (AKT)/mammalian target of rapamycin signaling pathway are involved in the progression of esophageal squamous cell carcinoma. By assessing the expression pattern of key components in the phosphoinositide-3 kinase/AKT/mammalian target of rapamycin signaling pathway by immunohistochemistry in tumor and nontumor esophageal mucosa from patients with esophageal squamous cell carcinomas, we aimed to carefully explore the relationship between the various protein expressions and clinicopathological factors, as well as patient outcome. A total of 145 tumor and 145 nontumor samples from patients with esophageal squamous cell carcinoma, collected from HuaShan Hospital (Shanghai, China) were evaluated. Clinical characteristics, the targeted protein expressions (including phosphatase and tensin homolog, phosphoinositide-3 kinase, AKT, p-AKT, mammalian target of rapamycin, p-mTOR, p70S6 kinase 1, p-P70S6K1, elongation initiation factor 4E binding protein-1, and p-4E-BP1, and survival rate were analyzed. Among them, phosphoinositide-3 kinase, AKT, p-AKT, mammalian target of rapamycin, p-mTOR, elongation initiation factor 4E binding protein-1, p70S6 kinase 1, and p-P70S6K1 proteins were significantly upregulated in tumor tissue. Conversely, phosphatase and tensin homolog was largely downregulated in tumor tissue, notably in pT3-T4 tumors. Low expression of phosphatase and tensin homolog whereas high expression of mammalian target of rapamycin signaling components in tumors was closely related to the presence of lymph node metastases and advanced TNM stage (all P < .05). Moreover phosphatase and tensin homolog, mammalian target of rapamycin, and p70S6 kinase 1 were correlated with overall survival as well as p-mTOR was correlated with progression-free survival (all P < .05). Overexpression of mammalian target of rapamycin was proved to be an independent adverse prognostic factor for overall survival in esophageal squamous cell carcinomas. Our results suggest that the phosphoinositide-3 kinase/AKT/mammalian target of rapamycin signaling pathway is activated in esophageal squamous cell carcinoma, with the low expression of phosphatase and tensin homolog and the high expression of the mammalian target of rapamycin component proteins (both total and phosphorylated) in tumor tissue. Our result might offer a new strategy for specific targeted therapy and prognostic assessment in esophageal cancer.

A Malformed Staple Causing Cardiac Tamponade After Lobectomy

We present a patient with cardiac tamponade caused by a malformed staple after lobectomy. The patient was successfully rescued by an urgent reoperation. Although rare, acute cardiac tamponade should be taken into account after lobectomy, and proper measures should be taken against the potential harm caused by a malformed staple.

Primary Esophageal CD30-Positive ALK-Positive Anaplastic Large Cell Lymphoma: A Case Report and Literature Review

PurposeTo introduce a case of primary esophageal CD30-positive ALK-positive anaplastic large cell lymphoma (ALCL) and discuss its diagnosis and treatment.MethodsEsophagectomy was done for a 37-year-old male with a submucosal lesion after a frozen section failed to give a definite diagnosis. Samples were sent for hematoxylin–eosin staining and immunohistochemical analysis. Six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy were given and the patient was followed up.ResultsThe operation was uneventful. Postoperative pathologic and immunohistochemical examination yielded a diagnosis of primary CD30-positive and ALK-positive ALCL of the esophagus. The patient was in complete remission at the 14-month follow-up.ConclusionsALCL of the esophagus should be considered in the differential diagnosis of esophageal submucosal lesions. Biopsy through either esophagoscopy or surgical exploration, chemotherapy, and radiotherapy can be chosen for long-term survival.

Increased frequency of thymic T follicular helper cells in myasthenia gravis patients with thymoma

BACKGROUND To investigate the presence of T follicular helper (TFH) cells and their associated molecules in myasthenia gravis (MG) patients with thymoma. METHODS TFH cells are detected in thymus around the thymoma region of 50 patients and atrophic thymus in 10 patients as control. The percentage of TFH cells among CD4(+) T cells and the expression level of surface markers CXC chemokine receptor 5 (CXCR5), inducible co-stimulator (ICOS), programmed cell death 1 and the cytoplasmic marker B cell lymphoma 6 (Bcl-6) were analyzed by immunohistochemistry (IHC) staining, immunofluorescence (IF) and western blotting (WB). RESULTS Higher percentage of thymic TFH cells was found in MG patients with thymoma compared with both thymoma patients without MG and control group. The expression levels of the four markers in thymoma of MG patients were significantly higher than thymoma patients without MG and control group. No significant difference was found in the levels of programmed cell death 1 (PD-1) and Bcl-6 between thymoma patients without MG and the control, while the levels of CXCR5 and ICOS in thymoma patients without MG were higher than control group. CONCLUSIONS These results suggested thymic TFH cells might involve in the pathogenesis of MG with thymoma. However, it needs further study to test if the inhibition of the function of TFH cells could effectively alleviate the severity of MG.