Abstract. The aim of the present study was to investigate the renoprotective effects of isorhamnetin (ISO) in type 2 diabetic rats and its effects on the nuclear factor-κB (NF-κB) signaling pathway, which is associated with diabetic nephropathy. The type 2 diabetic rat model was established by a high-fat diet plus streptozocin injection and the rats were subsequently treated with two dosages of ISO, respectively. The levels of blood glucose were determined. Urinary osteopontin, kidney injury molecule-1 (KIM-1) and albumin were measured to evaluate the renal function of the rats. Renal NF-κB signaling activity was assessed by measuring the levels of NF-κB p65, phospho-NF-κB p65, inhibitor of NF-κB (IκBα) and phospho-IκBα, and the NF-κB p65 DNA-binding activity. Downstream inflammatory mediators [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-β1 (TGF-β1)] of the NF-κB signaling pathway were investigated to evaluate the renal inflammatory response. Renal levels of malondialdehyde and total superoxide dismutase were detected to access the oxidative stress. Furthermore, glomerular mesangial cells (GMCs) were treated with lipopolysaccharide and ISO. In the cellular experiment, the NF-κB signaling activity, levels of TNF-α, IL-1β, IL-6, ICAM-1 and TGF-β1, and oxidative stress were also investigated. The results showed that ISO decreased the levels of urinary osteopontin, KIM-1 and albumin. ISO also inhibited the NF-κB signaling activity, decreased the production of inflammatory mediators and attenuated oxidative stress in diabetic rats and GMCs. The present investigations revealed that ISO had ameliorative effects on diabetes-induced renal damage and the activity may be associated with the negative regulation of NF-κB signaling pathway.

This study aimed to investigate the effects of silencing the speckle-type POZ protein (SPOP) gene on renal cell cancer (RCC) cells and to explore its possible mechanism. The A498 and ACHN RCC cells were transfected with small interference RNA (siRNA)-SPOP by lipofection methods. The silencing efficiency was monitored by quantitative real-time polymerase chain reaction and Western blot. The effects of SPOP silencing on cell apoptosis, cell viability, colony formation ability, cell migration ability, and chemosensitivity to Sorafenib were assessed by flow cytometry, an MTT assay, a colony formation assay, a trans-well migration assay, and a CCK-8 assay, respectively. Its effects on the expression of several cytokines were determined by a protein microarray. Relevant signaling pathways were also analyzed. Compared with the control group, the cell apoptosis rate was significantly higher; the cell viability, the colony formation, and migration ability were significantly decreased in the siRNA-SPOP group. The protein microarray screening showed that the expression of vascular endothelial growth factor receptor, matrix metallopeptidase-9, vascular cell adhesion molecule-1, and stromal cell-derived factor-1 in the siRNA group was significantly decreased and that the expression of granulocyte–macrophage colony-stimulating factor and E-cadherin was significantly increased (P<0.05). The relevant signaling pathways were the integrin-mediated cell surface interactions pathway and extracellular matrix organization signal pathway. SPOP gene silencing induced cell apoptosis, decreased cell viability, colony formation, and migration ability, and elevated the drug sensitivity in the RCC cells. A possible mechanism is that silencing SPOP induces the differential expression of E-cadherin, vascular endothelial growth factor receptor, matrix metallopeptidase-9, and vascular cell adhesion molecule, which are related to the integrin-mediated cell surface interactions and extracellular matrix organization signaling pathway.

ABSTRACT.To investigate the effects of probucol on the treatment of spinal cord injury in rat, 80 rats were randomly divided into two groups of 40: a group treated with probucol and a control group. Allen's method was used to establish a rat model of spinal cord injury. After establishment, probucol (500 mg·kg -1 ·day -1 ) was intraperitoneally injected into the treatment group rats for 1 week, while the same amount of saline was used to treat the control group. On days 1, 7, 14, 21, and 28 after treatment, the function of rats' spinal cord was evaluated according to the Bresnahan locomotor rating scale. Serum protein and mRNA levels of the cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-17] were measured using enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. Protein levels of IFN-γ, TNF-α, IL-17, and the downstream markers signal transducer and activator of transcription (STAT)-1 and STAT-3 were measured using western blot. In addition, the oxidative stress-related parameters, superoxide dismutase (SOD) and malondialdehyde (MDA), were also measured. It was found that compared to control group, rats from the treatment group had significantly lower levels of IFN-γ, TNF-α, and IL-17 (P < 0.05) on days 1 and 7, as well as lower MDA levels and higher SOD activity on days 7, 21, and 28 (P < 0.05). In summary, probucol improved the recovery of locomotion function after spinal cord injury in rats through downregulation of inflammation and upregulation of anti-oxidative activity.

Purpose: To investigate the protective effect of liraglutide on myocardial ischemia reperfusion (I/R) injury and its molecular mechanism.Methods: Ischemia reperfusion model male Sprague-Dawley (SD)