Predictive value of monocyte to HDL-C ratio for coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease.

We aimed to investigate the predictive validity of monocyte to high-density lipoprotein cholesterol ratio (MHR) for coronary artery lesions (CALs) and intravenous immunoglobulin (IVIG) resistance in complete Kawasaki disease (KD). MHR values of a total of 207 complete KD patients were calculated and analyzed with regard to their clinical characteristics and outcomes. We compared the differences in clinical data and laboratory parameters between CAL+ group and CAL- group as well as between IVIG-resistant group and IVIG-responsive group. Spearman's correlation analysis was applied to evaluate the correlation between C-reactive protein (CRP) and MHR. Multivariate logistic regression was used to identify risk factors of CALs and IVIG resistance. Receiver operating characteristic (ROC) curve analysis was chosen to determine the optimal cut-off value of MHR and its validity in predicting CALs and IVIG resistance. The MHR level was significantly higher in the CAL+ group, with cut-off value of 1.30 g/L, yielding a sensitivity of 0.753 and specificity of 0.805, as well as in IVIG-resistant group, with cut-off value of 1.03 g/L, yielding a sensitivity of 0.97 and specificity of 0.485. Multivariate logistic regression showed that MHR was an independent risk factor for CALs but not for IVIG resistance. According to the Spearman's correlation analysis, CRP was positively correlated with the MHR. CONCLUSIONS: As a practical, cost-effective inflammatory biomarker, MHR has a significantly predictive value in complete KD children complicated with CALs and IVIG-resistance. Paying more attention to the changes of MHR in KD children may contribute to better understanding of KD development and prognosis in clinical practice. WHAT IS KNOWN: • CALs are the most prevalent serious sequela of KD, and approximately 10%~20% of patients do not respond to IVIG therapy. • MHR could be a convenient biomarker to predict the development and progression of CVDs. It has been reported that the MHR is a new prognostic biomarker in several CVDs. WHAT IS NEW: • MHR has a significantly predictive value in KD children complicated with CALs and IVIG-resistance. • Compared with the molecular and immunological biomarkers that have been reported, MHR has the characteristics of practical, cost-effective, higher sensitivity and specificity, which can be used as a predictive indicator in complete KD patients.

Inhibitor of DNA-binding-1/inhibitor of differentiation-1 (ID-1) is implicated in various aspects of gastric cancer cell biology.

In order to determine the biological roles of the inhibitor of DNA-binding-1/inhibitor of differentiation-1 (ID-1) protein in MGC803 and AGS cell lines, we ectopically expressed or downregulated ID-1 in the both gastric cell lines and measured various parameters of tumor cell development, including cell proliferation, cell cycle progression, apoptosis and cell migration. The ectopic expression of ID-1 significantly enhanced cell proliferation, cell cycle progression and cell migration, and protected MGC803 and AGS cell lines from cisplatin-induced apoptosis. The opposite effects were observed after downregulation of ID-1, which in combination with cisplatin treatment enhanced apoptosis in a synergistic fashion. Collectively, these findings demonstrate that ID-1 plays pivotal and diverse roles in the biology of certain gastric cancer cells, further suggesting that ID-1 is implicated in the pathogenesis and progression of gastric cancer.

Inhibition of rho kinase attenuates high flow induced pulmonary hypertension in rats.

BACKGROUND: The RhoA/Rho kinase pathway may participate in the pathogenesis of hypoxia and monocrotaline induced pulmonary hypertension. This study tested whether RhoA/Rho kinase pathway is involved in the pathogenesis of high flow induced pulmonary hypertension in rats. METHODS: Male Wistar rats (4 weeks) were randomly divided into 4 shunt groups, 4 treated groups and 4 control groups. Shunt and treated groups underwent left common carotid artery/external jugular vein shunt operation. Control groups underwent sham operation. Treated groups received fasudil treatment and the others received same dose of saline. At weeks 1, 2, 4 and 8 of the study, right ventricular systolic pressure was measured and blood gases were analysed to calculate Qp/Qs. The weight ratio of right ventricle to left ventricle plus septum and the mean percentage of medial wall thickness in moderate sized pulmonary arteries were obtained. RhoA activity in pulmonary arteries was detected using Rho activity assay reagent. Rho kinase activity was quantified by the extent of MYPT1 phosphorylation with Western blot. Proliferating cells were evaluated using proliferating cell nuclear antigen immunohistological staining. RESULTS: Carotid artery/jugular vein shunt resulted in high pulmonary blood flow, both an acute and a chronic elevation of right ventricular systolic pressure, significant medial wall thickening characterized by smooth muscle cells proliferation, right ventricular hypertrophy and increased activation of RhoA and Rho kinase. Fasudil treatment lowered pulmonary artery systolic pressure, suppressed pulmonary artery smooth muscle cells proliferation, attenuated pulmonary artery medial wall thickening and inhibited right ventricular hypertrophy together with significant suppression of Rho kinase activity but not Rho activity. CONCLUSIONS: Activated RhoA/Rho kinase pathway is associated with both the acute pulmonary vasoconstriction and the chronic pulmonary artery remodelling of high flow induced pulmonary hypertension. Fasudil treatment could improve pulmonary hypertension by inhibiting Rho kinase activity.

[Roles and signal pathways of adrenomedullin and adrenotensin in pulmonary remodeling due to left to right shunt in rats].

OBJECTIVES: The effect of vascular active peptides on the development of pulmonary remodeling and pulmonary hypertension due to left to right shunt congenital heart diseases is the focus of today's studies. The present study was conducted to investigate the roles of adrenomedullin (ADM) and adrenotensin (ADT) in pulmonary remodeling due to left to right shunt in rat lungs. METHODS: Twenty-one male Wistar rats were divided into two groups randomly. A right common carotid artery to external jugular vein shunt operation was performed on experimental rats (n = 9) to establish a left to right shunt animal model. Meanwhile, the common carotid artery and external jugular vein of the control group rats (n = 12) were just isolated without connection. Twelve weeks later, the mean pulmonary artery pressure (mPAP), the right ventricle to left ventricle plus septum ratio [weight, RV/(LV + SP)], the percentage of media wall thickness (MT%) were calculated. The distributions and relative protein contents of ADM and ADT in lungs were measured by immunohistochemical staining and Western blotting analysis. The relative gene expression for ADM, ADT, p46-p54 stress-actived protein kinase (SAPK) and p44 extracellular signal-regulated protein kinase 1 (ERK(1)) were investigated by RT-PCR. RESULTS: The muscular and the tunica intimae layer of pulmonary artery were thicker in experiment group rats than those of control group, and the mPAP increased significantly in shunt group [(27.10 +/- 6.67) mm Hg (1 mm Hg = 0.133 kPa)] compared with that in control group [(14.32 +/- 3.14) mm Hg] (t = 5.5507, P < 0.001). The ratios of RV/(LV + SP) and MT% increased significantly in experimental group in contrast to the control group (P < 0.001). ADM and ADT positive granules distributed mainly over vascular smooth muscle cells, and Western blotting and integrated optical density analysis showed that the content of ADM increased in shunt group rats (P < 0.001), however, ADT content decreased (P < 0.001). The mRNA expression of ADM, SAPK and ERK(1) up-regulated in experiment group compared with the control group (P < 0.01, and P < 0.001 respectively), however, the ADT mRNA expression decreased in experimental rats in contrast to the control group (P < 0.001). CONCLUSIONS: The phenomenon of intramolecular regulation of ADM and ADT, which both derived from proadrenomedullin, existed in the development of pulmonary remodeling and pulmonary hypertension due to left to right shunt. The mitogen-activated protein kinases (MAPKs) signal transduction pathway has been activated in the formation of left to right shunt pulmonary remodeling and pulmonary hypertension, and ADM may slow down the occurrence of pulmonary hypertension through cutting off MAPKs signaling pathway.