Retraction Note: Tert-butylhydroquinone lowers blood pressure in AngII-induced hypertension in mice via proteasome-PTEN-Akt-eNOS pathway.

This article has been retracted.

2,3,5,4'­Tetrahydroxystilbene­2­O­ß­D­glucoside inhibits septic serum­induced inflammatory injury via interfering with the ROS­MAPK­NF­κB signaling pathway in pulmonary aortic endothelial cells.

Sepsis is characterized by injury to the microvasculature and the microvascular endothelial cells, leading to barrier dysfunction. However, the specific role of injury in septic endothelial barrier dysfunction remains to be elucidated. In the present study, it was hypothesized that endothelial cell inflammatory injury is likely required for barrier dysfunction under septic conditions in vitro. 2,3,5,4'­Tetrahydroxystilbene­2­O­ß­D­glucoside (TSG), a compound extracted from Chinese herbs, is able to inhibit the inflammatory injury of septic­serum in endothelial cells. In the present study, cell viability was assayed by CCK­8 method; mRNA and protein expression was identified by RT­qPCR, western blot or Elisa, respectively and the production of reactive oxygen species was observed by a fluorescence microscope. The present study indicated that septic serum significantly decreased the cell viability of pulmonary aortic endothelial cells (PAECs) following co­cultivation for 6 h, which occurred in a time­dependent manner. TSG notably increased the viability of PAECs in a time­ and concentration­dependent manner. Further investigations revealed that septic serum increased the secretion of interleukin (IL)­1ß, IL­6 and C­reactive protein in PAECs, whereas pretreatment with TSG significantly decreased the secretion of these inflammatory factors. These data indicated that septic serum increased inflammatory injury to the PAECs, and TSG decreased this injury via the reactive oxygen species­mitogen­activated protein kinase­nuclear factor­κB signaling pathway.

Tert-butylhydroquinone lowers blood pressure in AngII-induced hypertension in mice via proteasome-PTEN-Akt-eNOS pathway.

Tert-butylhydroquinone (tBHQ), as an antioxidant, has been widely used for many years to prevent oxidization of food products. The aim of this study was to investigate whether tBHQ activates endothelial nitric oxide synthase (eNOS) to prevent endothelial dysfunction and lower blood pressure. The role of Akt in tBHQ-induced eNOS phosphorylation was examined in human umbilical vein endothelial cells (HUVEC) or in mice. tBHQ treatment of HUVEC increased both Akt-Ser473 phosphorylation, accompanied with increased eNOS-Ser1177 phosphorylation and NO release. Mechanically, pharmacologic or genetic inhibition of Akt abolished tBHQ-enhanced NO release and eNOS phosphorylation in HUVEC. Gain-function of PTEN or inhibition of 26S proteasome abolished tBHQ-enhanced Akt phosphorylation in HUVEC. Ex vivo analysis indicated that tBHQ improved Ach-induced endothelium-dependent relaxation in LPC-treated mice aortic arteries, which were abolished by inhibition of Akt or eNOS. In animal study, administration of tBHQ significantly increased eNOS-Ser1177 phosphorylation and acetylcholine-induced vasorelaxation, and lowered AngII-induced hypertension in wildtype mice, but not in mice deficient of Akt or eNOS. In conclusion, tBHQ via proteasome-dependent degradation of PTEN increases Akt phosphorylation, resulting in upregulation of eNOS-derived NO production and consequent improvement of endothelial function in vivo. In this way, tBHQ lowers blood pressure in hypertensive mice.

Artemisinin protects mice against burn sepsis through inhibiting NLRP3 inflammasome activation.

BACKGROUND: NLRP3 inflammasome activation is recently reported to be linked to the pathogenesis of sepsis. Artemisinin is shown to play beneficial effects in sepsis. However, the impacts of artemisinin on burn sepsis have not been investigated. This study is designed to investigate the role of artemisinin in burn sepsis and the involvement of NLRP3 inflammasome activation. METHODS: Male BALB/c mice were randomly divided into sham burn, burn, burn sepsis, and artemisinin treated groups. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay. Adhesion molecules and neutrophil infiltration in lung and heart were detected by real-time polymerase chain reaction. Mortality rates were monitored. Artemisinin was added to Raw 264.7 cells that were stimulated with burn sepsis serum in the presence/absence of an inhibitor of NLRP3 inflammasome, 3, 4-methylenedioxy-ß-nitrostyrene. Interleukin (IL) 1ß and IL-18 messenger RNA expression as well as NLRP3 and caspase 1 protein were measured. RESULTS: Production of inflammatory cytokines in serum, levels of adhesion molecules and neutrophil infiltration in lung and heart, and mortality rate of burn septic mice were significantly higher than those of control. These effects were attenuated by artemisinin. Artemisinin down-regulated protein levels of NLRP3 and caspase 1 and inhibited the increases of IL-1ß and IL-18 messenger RNA expression from Raw 264.7 cells that were stimulated with burn sepsis serum. These effects of artemisinin were not further strengthened in the presence of 4-methylenedioxy-ß-nitrostyrene. CONCLUSION: Artemisinin protects mice from burn sepsis by attenuating the inflammatory response and alleviating inflammatory infiltration in vital organs, likely through inhibiting the activation of NLRP3 inflammasome.

Metallothionein ameliorates burn sepsis partly via activation of Akt signaling pathway in mice: a randomized animal study.

INTRODUCTION: Metallothioneins (MTs) are a family of cysteine-rich and low molecular-weight proteins that can regulate metal metabolism and act as antioxidants. Recent studies showed that MTs played a protective role in excessive inflammation and sepsis. However, the role of MTs in burn sepsis remains unclear. This study is designed to investigate the role of MTs in burn sepsis in an experimental mouse model. METHODS: MT-I/II knockout (-/-) mice on a C57BL/6 background and their wild-type (WT) littermates were randomly divided into sham burn, burn, burn sepsis, Zn treated and Zn-MT-2 treated groups. Levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Myeloperoxidase (MPO) activity was detected by spectrophotometry. In in vitro study, exogenous MT was added to macrophages that stimulated with serum from burn sepsis mice with or without Akt inhibitor LY294002. The IL-1 ß and IL-6 mRNA expression were detected by quantitative real-time polymerase chain reaction. The levels of Akt expression were determined by western blot. RESULTS: Burn sepsis induced significantly elevated levels of inflammatory cytokines in serum and increased inflammatory infiltration in the liver and lung. These effects were more prominent in MT (-/-) mice than in WT mice. Furthermore, exogenous MT-2 inhibited these elevated inflammatory response in both WT and MT (-/-) mice. MT-2 up-regulated Akt phosphorylation and abrogated the increase of IL-1ß and IL-6 mRNA expression from macrophages that stimulated with burn sepsis serum. These effects of MT-2 were abolished in the presence of LY294002. CONCLUSION: MT-2 ameliorates burn sepsis by attenuating inflammatory response and diminishing inflammatory organ damage, which is at least partly mediated by activation of Akt signaling pathway.

Apelin attenuates postburn sepsis via a phosphatidylinositol 3-kinase/protein kinase B dependent mechanism: A randomized animal study.

INTRODUCTION: This study aims to investigate whether apelin would regulate inflammatory response and promote survival in an experimental burn sepsis model through a phosphatidylinositol 3-kinase/protein kinase B dependent pathway. METHODS: Male BALB/c mice were divided into the following groups: sham, burn, burn sepsis, burn sepsis treated with apelin, burn sepsis treated with apelin plus LY294002, and burn sepsis treated with LY294002 alone. Apelin level and inflammatory cytokines in serum were detected by enzyme-linked immuno sorbent assay. Apelin/APJ (apelin receptor, gene symbol APLNR) mRNA expression in spleen and adhesion molecules levels in lung was detected by real-time polymerase chain reaction. Neutrophil infiltration in lung was determined by myeloperoxidase assay. Phosphorylation of protein kinase B in lung was determined by western blot. Mortality rate was monitored. RESULTS: Burn sepsis induced decreased apelin/APJ mRNA expression in spleen and reduced apelin level in plasma, which were both restored by exogenous apelin treatment. Burn sepsis treated with apelin resulted in decreased interleukin-6, tumor-necrosis factor-alpha, interleukin -1ß and monocyte chemotactic protein-1 levels in plasma. Mice with apelin treatment also showed decreased neutrophil infiltration and adhesion molecules expression, accompanied by a remarkable increased protein kinase B phosphorylation in lung tissue. The mortality rate in apelin treated animals was also significantly reduced. Importantly, the above effects of apelin were abolished by LY294002 treatment. CONCLUSION: Apelin regulates inflammatory response, diminishes inflammatory remote organ damage and improves survival in an experimental model of burn sepsis, which is at least partly mediated by a phosphatidylinositol 3-kinase/protein kinase B dependent pathway.

Reduced apoptosis after acute myocardial infarction by simvastatin.

To observe the effect of simvastatin in patients with acute myocardial infarction in rabbits against myocardial apoptosis, and to explore its possible mechanism. Male New Zealand white rabbits were randomized into three groups, including the myocardial infarction group (12 rabbits), the simvastatin treatment group (15 rabbits), and the sham group (12 rabbits). In the simvastatin treatment and myocardial infarction groups, the rabbits received myocardial infarction surgeries. While in the sham group, loose knots were tied in the left anterior descending coronary artery branches. The simvastatin treatment group was given simvastatin by oral gavage 24 h after surgery. Parameters, which included left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular ejection fraction, and left ventricular mass index, were recorded in these three groups. Edge myocardial infarction and myocardial cell apoptosis were analyzed using TUNEL assay, and Bcl-2, Bax, and Caspase-3 protein levels were detected by Western blot. Acute myocardial infarction model was successfully established in rabbits by ligation of the left anterior descending coronary artery. Compared with the myocardial infarction group, left ventricular end-diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) were significantly reduced and left ventricular ejection fraction (LVEF) increased in the simvastatin treatment group. Compared with the sham group, LVEDD and LVESD were significantly increased and LVEF decreased in the simvastatin treatment group. All the differences were statistically significant (P < 0.05). Left ventricular mass index in the simvastatin treatment group was statistically lower than the myocardial infarction group. Compared with the sham group, left ventricular mass index in both the simvastatin treatment and myocardial infarction groups was significantly increased. The differences of the above comparisons were statistically significant (P < 0.05). Compared with the sham group, the apoptosis rate of the myocardial infarction group and the simvastatin treatment groups was significantly increased as shown by TUNEL assay, however, the apoptosis rate of the simvastatin treatment group was significantly lower than that of the myocardial infarction group. All the differences among above comparisons were statistically significant (P < 0.05). Bcl-2 levels significantly increased in the simvastatin treatment group compared with the myocardial infarction group, but Bcl-2 levels in both groups were significantly lower than the sham group. However, Bax protein levels showed inverse expression with Bcl-2. Meanwhile, Caspase-3 protein expression showed similar trend with Bcl-2. Simvastatin can improve cardiac function after myocardial infarction and reduce apoptosis of myocardial cells, possibly by decreasing Bax and Caspase-3 expression and increasing the expression level of Bcl-2.

The effect of chemokine CC motif ligand 19 on the proliferation and migration of hepatocellular carcinoma.

Multiple studies have shown that CC motif chemokine ligand 19 (CCL19) promotes cell proliferation in several human cancers. The aim of this study was to investigate the expression and function of CCL19 in hepatocellular carcinoma (HCC). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry were performed separately to detect the expression of CCL19 in HCC tissues. The expression of CCL19 and its receptor (CCR7) in different HCC cell lines were screened by Western blot. HCC cell lines were screened and processed with recombinant human CCL19 (rhCCL19) or si-CCL19 RNA. Cell proliferation assay and transwell assay were performed to evaluate the proliferation and migration of HCC cells, respectively. Low expression of CCL19 was observed in 83.72 % (72/86) of the HCC versus 16.67 % (4/24) of the adjacent non-tumorous liver tissues, the difference of CCL19 expression between HCC and adjacent non-tumorous liver tissues was statistically significant (P < 0.001). The expression level of CCL19 mRNA and protein in tumor tissues was significantly lower than adjacent non-tumorous liver tissues. The proliferation and migration of HCC cells were obviously inhibited in rhCCL19-treated groups. Our data suggest that CCL19 may play a suppressive role in the regulation of aggressiveness in human HCC.

Association between arterial stiffness and risk of coronary artery disease.

OBJECTIVE: To investigate the role of Brachial ankle Pulse Wave Relocity (baPWV) and cfPWV on the risk of Coronary artery disease and the interaction between baPWV and risk factors of Coronary artery disease (CAD). METHODS: A case-control study was conducted at Department of Emergency, SunYat-Sen memorial Hospital, China. We collected 332 cases with coronary artery disease and 328 subjects without CAD between February 2012 and October 2013. A multivariate logistic regression analysis was performed to analyze the risk factors of CAD. RESULTS: CAD subjects were more likely to be old age, and have higher BMI, waist-hip ratio, hypertension, fasting glucose, TG, carotid-femoral PWV (cfPWV) and baPWV, and CAD subjects had a lower TC, HDL-C and LDL-C. We found that older age, smoking, higher hypertension, TC, TG, HDL-C, LDL-C, carotid-femoral PWV (CfPWV) and baPWV were associated with risk of CAD. baPWV had significant interaction with age, TC, TG, HDL-C and LDL-C, carotid-femoral PWV (cfWV) was correlated with age, HDL-C and LDL-C. CONCLUSION: This study showed that baPWV and cfPWV are two independent factors for the risk of Coronary artery disease, and baPWV and cfPWV have interaction with age, TC, TG, HDL-C and LDL-C.

[Carcinoembryonic antigen increased as initial manifestation of medullary thyroid cancer (report of 2 cases and review of the literature)].

OBJECTIVE: To raise clinical awareness of carcinoembryonic antigen(CEA) increased as initial manifestation of medullary thyroid cancer(MTC) and explore the diagnosis and treatment. METHOD: Clinical data of 2 cases CEA increased as the initial presentation of MTC were retrospectively analyzed and clinical manifestations of the disease, diagnosis, treatment were also discussed by literature reviewing. RESULT: Two patients received thyroid ipsilateral lobe total resection, MTC was confirmed by intraoperative frozen pathology, re-total resection of the contralateral lobe and bilateral VI lymph node dissection were performed. Lymph nodes had no metastasis confirmed by pathological frozen examination. CEA returned to normal within 2 months after surgery. No tumor recurrence and metastasis were found after follow-up for 3 to 24 months. CONCLUSION: CEA increased as the initial presentation MTC was rare and clinical identification of CEA increased disease should be taken into account the MTC as possible. Total thyroidectomy and bilateral VI lymph node dissection was the main surgical treatment for it.

Polymorphisms in DNA repair genes and risk of glioma and meningioma.

Polymorphisms in DNA repair genes have been shown to influence DNA repair processes and to modify cancer susceptibility. Here we conducted a case-control study to assess the role of potential SNPs of DNA repair genes on the risk of glioma and meningioma. We included 297 cases and 458 cancer-free controls. Genotyping of XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met, XRCC4 Ala247Ser, ERCC1 Asn118Asp, ERCC2 Lys751Gln and ERCC5 Asp1558His were performed in a 384-well plate format on the Sequenom MassARRAY platform. XRCC1 Arg194Trp (rs1799782) and ERCC2 Asp312Asn rs1799793 did not follow the HWE in control group, and genotype distributions of XRCC1 Gln399Arg rs25487, XRCC2 Arg188His rs3218536 and ERCC2 Asp312Asn rs1799793 were significantly different between cases and controls (P<0.05). We found XRCC1 399G/G, XRCC1 194 T/T and XRCC3 241T/T were associated with a higher risk when compared with the wild-type genotype. For ERCC5 Asp1558His, we found G/G genotype was associated with elevated susceptibility. In conclusion, our study has shown that XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC3 Thr241Met and ERCC5 Asp1558His are associated with risk of gliomas and meningiomas. This finding could be useful in identifying the susceptibility genes for these cancers.