Liraglutide improves atherosclerosis by regulating long non-coding RNA RMRP/miR-128-1-5P/Gadd45g axis.

OBJECTIVE: Recent studies indicated that long non-coding RNA is involved in the formation of atherosclerosis, which is the pathological basis of coronary heart disease. Here, we reported the function and regulatory mechanism of RMRP in coronary atherosclerosis. MATERIALS AND METHODS: qPCR was used to investigate the expression of IL-6, IL-8, RMRP, and miR-128-1-5P in coronary atherosclerosis and human vascular smooth muscle cells. Luciferase reporter assay confirmed the direct target effect of RMRP with miR-128-1-5P and miR-128-1-5P with Gadd45g on HEK293T. Western blot was used to detect protein expression in coronary atherosclerosis and human vascular smooth muscle cells. RESULTS: RMRP expression and Gadd45g protein level were up-regulated in coronary atherosclerosis and human vascular smooth muscle cells, while miR-128-1-5P was down-regulated. RMRP downregulation remarkably inhibited the expression of IL-6, IL-8, and apoptosis related protein in human vascular smooth muscle cells after ox-LDL treatment. In addition, bioinformatics analysis and Luciferase report experiments confirmed that RMRP was the direct target of miR-128-1-5P. Moreover, miR-128-1-5P inhibitor reserved evidently the effect of IL-6, IL-8, and apoptosis related protein induced RMRP-si after treatment of human vascular smooth muscle cells with ox-LDL, implying RMRP negatively and directly regulated miR-128-1-5P in coronary atherosclerosis. More importantly, RMRP silencing increased Gadd45g protein level in human vascular smooth muscle cells. The same results were found when miR-128 was upregulated. Meanwhile, Gadd45g-si extremely reversed the result of IL-6, IL-8, and apoptosis related protein induced miR-128-1-5P inhibitor after treatment of human vascular smooth muscle cells with ox-LDL and Luciferase report experiments showed that Gadd45g was a direct target of miR-128-1-5P, implying Gadd45g negatively and directly regulated miR-128-1-5P in coronary atherosclerosis. Furthermore, liraglutide restrained evidently the expression of IL-6, IL-8, and apoptosis related protein in coronary atherosclerosis. After all, these results showed that liraglutide could regulate RMRP/miR-128-1-5P/Gadd45g signal pathway to improve coronary atherosclerosis. CONCLUSIONS: Liraglutide could curb the expression of inflammatory cytokines and apoptosis related protein in coronary atherosclerosis by regulating RMRP/miR-128-1-5P/Gadd45g signaling pathway, providing a new potential strategy for the treatment of coronary atherosclerosis.

LncRNA SNHG16 promoted proliferation and inflammatory response of macrophages through miR-17-5p/NF-κB signaling pathway in patients with atherosclerosis.

OBJECTIVE: Atherosclerosis (AS) is a leading cause of cardiovascular disease (CVD), which is also the leading reason for mortality and morbidity worldwide. Growing evidence has shown that long non-coding RNAs (lncRNAs) play some roles in the development of AS; however, their roles remain unclear. In this study, we aimed to explore the function of lncRNA SNHG16 in AS. PATIENTS AND METHODS: qRT-PCR was used to detect the expressions of SNHG16 and miR-17-5p in AS serum samples and THP-1 macrophage-derived foam cells; the correlations were also analyzed. THP-1 macrophages were respectively treated with ox-LDL and several inflammatory factors to explore the affecting factors. What's more, SNHG16 overexpression lentivirus (LV-SNHG16) and downregulation lentivirus (LV-sh SNHG16) were purchased and infected into THP-1 macrophages. CCK8 assay was used to measure cell proliferation; the levels of IKKß, p-IkBα and p-p65 were detected by western blot (WB), and the levels of TNF-α, IL-1ß and IL-6 were detected by ELISA kit. Moreover, the luciferase assay was performed to explore the binding site of SNHG16 and miR-17-5p. Furthermore, we transfected miR-17-5p mimic and inhibitor into THP-1 macrophages; the proliferation, NF-κB signaling pathway factors and inflammatory factors were detected. Finally, JSH, a NF-κB signaling inhibitor, was added into LV-SNHG16 THP-1 macrophages and miR-17-5p inhibitor was transfected into LV-sh SNHG16 THP-1 macrophages to confirm that SNHG16 functions via miR-17-5p/ NF-κB signaling pathway. RESULTS: We found that SNHG16 was increased in AS patients and THP-1 macrophage-derived foam cells. Additionally, SNHG16 was increased in THP-1 macrophages by ox-LDL with time-dependence and dose-dependence. Furthermore, SNHG16 overexpression promoted proliferation, inflammatory response and increased levels of IKKß, p-IkBα, p-p65 in THP-1 macrophages, while SNHG16 downregulation led to the opposite results. Most importantly, we found that miR-17-5p expressions were significantly decreased in AS patients, which were negatively correlated with SNHG16. Luciferase gene reporter assay confirmed that SNHG16 could directly bind with miR-17-5p. Moreover, the proliferation, inflammatory factors and NF-κB signaling factors were significantly repressed after transfecting miR-17-5p mimic into THP-1 macrophages, while it led to the opposite results after transfecting miR-17-5p inhibitor. Then, we added JSH, a NF-κB signaling inhibitor, into LV-SNHG16 THP-1 macrophages; as a result, the increased cell proliferation rate and inflammatory response were both decreased. Finally, we found that the repressed cell proliferation, inflammatory factors and expressions of NF-κB signaling factors in LV-sh SNHG16 group were increased after co-transfected with miR-17-5p inhibitor. CONCLUSIONS: According to the results, we found that SNHG16 was upregulated in AS patients. Furthermore, we firstly found that SNHG16 was increased by ox-LDL in THP-1 macrophages. Most importantly, we uncovered a previously unappreciated SNHG16/miR-17-5p/ NF-κB signaling axis in promoting proliferation and inflammatory response in AS patients and THP-1 macrophages, which might provide a potential target for treating AS.

Serum troponin I concentrations assessed 18-24 hours after coronary artery bypass grafting are significant predictors of early patient prognosis.

OBJECTIVE: Coronary heart disease (CHD) is a frequent medical condition in developed countries and is one of the most serious diseases threatening patients' lives. Perioperative myocardial infarction is the major cause of perioperative cardiac death and cardiac arrest, but is difficult to be precisely identified by observing clinical symptoms or assessing cardiac enzyme levels or by ECG examination. Therefore, assessment of patient prognosis requires reliable predictors. In this regard, we tested the prognostic value of serum troponin I (TnI) concentrations. PATIENTS AND METHODS: 98 patients undergoing elective simple off-pump coronary artery bypass grafting were recruited. Venous blood samples were collected within 3-5 hours, 18-24 hours, and 36-48 hours post-operation, and associations of TnI concentrations with early outcomes measures (duration of assisted ventilation, length of stay in the ICU, length of postoperative stay, administration of antihypotensive medications, use of intra-aortic balloon pump, and ECG abnormalities) were evaluated. Correlations of postoperative TnI concentrations with the outcomes measures were analyzed by using median TnI concentrations as the cut-off value. RESULTS: TnI concentrations assessed within 18-24 hours post-operation showed significant associations with most tested outcome measures (p < 0.05 for four out of five comparisons). Furthermore, after building ROC curves, the highest AUC values (> 0.9) were also observed for TnI1 concentrations assessed within this time frame. The optimal cutoff value for TnI concentration was 1.78 ng/ml. CONCLUSIONS: TnI concentrations assessed within 18-24 hours after elective off-pump coronary artery bypass grafting can effectively predict early patient prognosis.

Studies on the role of plasminogen activators and plasminogen activator inhibitor type-1 in rat corpus luteum of pregnancy.

Luteal development and demise are characterized by substantial tissue destruction and remodeling, which is associated with local production of plasminogen activation. Recently we reported involvement of tissue-type plasminogen activator (tPA) in luteolysis in rhesus monkeys. In this study, we further investigated changes in expression of both tPA and urokinase-type plasminogen activator (uPA) activity during various developmental stages of rat corpus luteum (CL) of pregnancy and their possible physiological roles in luteolysis. Rat CL or dispersed luteal cells in vitro are capable of producing both tPA and uPA, and a plasminogen activator inhibitor type-1, in a stage-dependent manner. However, only tPA activity significantly increases in late phases of CL development. Furthermore, the increase in tPA activity in the CL is well correlated with a sharp decrease in luteal progesterone production. Addition of exogenous tPA to the luteal culture considerably decreases progesterone production. In contrast, immunoneutralization of endogenously produced tPA activity by inclusion of tPA monoclonal antibody in the culture results in a significant increase in luteal progesterone production. It is therefore suggested that tPA may also be involved in suppression of rat luteal function. This hypothesis is further supported by the findings that interferon-gamma significantly inhibits luteal basal and hCG-stimulated progesterone production and also stimulates basal and hCG-induced tPA activity. On the basis of the data provided in this study and similar findings in monkeys, we conclude that endogenously produced tPA in late phase of CL development may regulate luteal regression through local autocrine or paracrine action.

Relationship between microvascular structure and biological characteristics of giant cell tumour of bone.

The vascular architecture of bone giant cell tumor was observed histologically with resin cast technique and scanning electron microscopy. Three types of capillaries were noted in the tumor tissue: extruding club-like capillary in the outer zone of the tumor; sinusoid capillary running disorderly in the intermediate zone; cecum capillary in the central zone. The pattern of vascular structure was believed to be correlated with tumor growth.

Pyogenic liver abscess: clinical manifestations and value of percutaneous catheter drainage treatment.

One hundred and sixty-two patients with solitary or multiple pyogenic liver abscesses received surgical or medical treatment in the past 8 years. Fifty-seven patients were treated medically (medical group), 62 patients received medical treatment plus sonogram-guided percutaneous drainage (PCD group), and 43 patients received surgical drainage (surgical group). Aerobic gram-negative rods were the predominant causative microorganisms. Klebsiella pneumoniae was the most common microorganism, occurring in 46.9% (76/162) of the cases. Anaerobes occurred in 16.7% (27/162) of the cases. In the evaluation of treatment, the success rates for these three groups were: medical group, 59.6% (34/57); PCD group, 90.3% (56/62); and surgical group, 83.7% (36/43). This retrospective study confirms evidence from a small series that medical treatment plus percutaneous catheter drainage is efficient and more convenient than conventional surgical drainage for pyogenic liver abscesses. The frequent severe septic emboli to distant organs noted in this series (11.1%; 18/162) are quite unusual and should be anticipated in the future.

Causal bacteria of pyogenic liver abscess.

This is a review of bacteriologic data on 175 patients with pyogenic liver abscesses seen over a period of 8 years at Veterans General Hospital, Taipei, Taiwan. Positive cultures were obtained from liver aspirates in 151 of the 163 patients in which cultures were taken. One hundred and twenty patient specimens grew one isolate and 31 specimens grew two or more isolates. A total of 149 aerobic gram-negative rods, 25 aerobic cocci and 29 anaerobes were isolated. Ninety of the 159 patients from whom blood was taken had positive cultures. In 11 patients, two or more isolates were grown concurrently from the blood. A total of 87 aerobic gram-negative rods, 7 aerobic cocci and 10 anaerobes were isolated. Klebsiella pneumoniae was the most common microorganism, accounting for 50.8% of the cases. Other major pathogens were Escherichia coli (27.4%), anaerobes (15.4%), and viridans streptococci (6.2%).