Interfering with pak4 Protein Expression Affects Osteosarcoma Cell Proliferation and Migration.

PURPOSE: A number of studies have discovered various roles of PAK4 in human tumors, including osteosarcoma. However, the exact role of PAK4 in osteosarcoma and its mechanism have yet to be determined. Therefore, this study focused on interrogating the PAK4 effect on the proliferation and migration ability of osteosarcoma and its underlying mechanisms. MATERIALS AND METHODS: Western blot and QRT-PCR were utilized to quantify the PAK4 relative protein and mRNA levels. To measure cellular viability and mobility, the MTT and wound-healing assays were preferred. RESULTS: With the adenovirus-mediated overexpression of PAK4, the proliferation and migration of U2-OS and MG-63 osteosarcoma cells were stimulated. Furthermore, a liposome-mediated knockout of PAK4 will inhibit osteosarcoma cells from proliferating. In terms of mechanism, we observed the positive correlation of PAK4 expression with expression of P21, CyclinD1, CyclinE1, CDK2, and CDK6, which drives G0/G1 to the G2/M phase transition. PAK4 can also activate Erk expression in OS cells and induce EMT. CONCLUSION: Interfering with PAK4 protein expression has been shown to affect osteosarcoma proliferation and migration.

A Novel STAT3-Mediated GATA6 Pathway Contributes to tert-Butylhydroquinone- (tBHQ-) Protected TNFα-Activated Vascular Cell Adhesion Molecule 1 (VCAM-1) in Vascular Endothelium.

The activation of vascular cell adhesion molecule 1 (VCAM-1) in vascular endothelial cells has been well considered implicating in the initiation and processing of atherosclerosis. Oxidative stress is mechanistically involved in proatherosclerotic cytokine-induced VCAM-1 activation. tert-Butylhydroquinone (tBHQ), a synthetic phenolic antioxidant used for preventing lipid peroxidation of food, possesses strongly antioxidant capacity against oxidative stress-induced dysfunction in various pathological process. Here, we investigated the protective role of tBHQ on tumor necrosis factor alpha- (TNFα-) induced VCAM-1 activation in both aortic endothelium of mice and cultured human vascular endothelial cells and uncovered its potential mechanisms. Our data showed that tBHQ treatment significantly reversed TNFα-induced activation of VCAM-1 at both transcriptional and protein levels. The mechanistic study revealed that inhibiting neither nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nor autophagy blocked the beneficial role of tBHQ. Alternatively, tBHQ intervention markedly alleviated TNFα-increased GATA-binding protein 6 (GATA6) mRNA and protein expressions and its translocation into nucleus. Further investigation indicated that tBHQ-inhibited signal transducer and activator of transcription 3 (STAT3) but not mitogen-activated protein kinase (MAPK) pathway contributed to its protective role against VCAM-1 activation via regulating GATA6. Collectively, our data demonstrated that tBHQ prevented TNFα-activated VCAM-1 via a novel STAT3/GATA6-involved pathway. tBHQ could be a potential candidate for the prevention of proatherosclerotic cytokine-caused inflammatory response and further dysfunctions in vascular endothelium.

Correlation between red blood cell distribution width and cardiovascular events in the patients receiving peritoneal dialysis: A Strobe-compliant article.

There are few studies on the correlation between red blood cell distribution width (RDW) and cardiovascular events in the patients receiving peritoneal dialysis (PD). We explored the correlation between RDW and cardiovascular events in PD patients and possible mechanism.A total of 138 PD patients were divided into RDW < 15% group (n = 104) and RDW ≥ 15% group (n = 34).The levels of serum C-reactive protein (CRP) [3.05 (0.79, 15.30) mg/L vs 2.15 (1.00, 6.50) mg/L] and parathyroid hormone (PTH) [260.0 (192.7, 352.6) ng/L vs 200.7 (118.0, 319.7) ng/L] were significantly higher, but the levels of serum albumin [30.65 (27.4,32.8) g/L vs 32.3 (29.25,34.95) g/L], prealbumin [(299 ±â€Š96) g/L vs (346 ±â€Š86) g/L], triglyceride [1.24 (0.72, 1.50) mmol/L vs 1.42 (1.12,1.84) mmol/L], and transferrin saturation [27.9 (16.4, 43.6)% vs 37.8 (23.3, 57.2)%] were significantly lower in the RDW ≥ 15% group than in the RDW < 15% group (all P < 0.05). The RDW was negatively correlated with albumin (r = - 0.258, P = 0.002), prealbumin (r = -0.236, P = 0.005), and triglyceride (r = -0.194, P = 0.023), but was positively correlated with CRP level (r = 0.174, P = 0.041). The incidence of cardiovascular events was significantly higher in the RDW ≥ 15% group (6 patients, 17.6%) than in the RDW < 15% group (6.7%) (7 patients, P < 0.01). Cox proportional hazard model showed that elevated RDW level was an independent risk factor for cardiovascular events in PD patients (HR = 1.622, 95% CI: 1.063-2.475, P = 0.025).The elevated RDW may be served as a risk factor to predict the cardiovascular events in PD patients.