(Fe 2ϩ ), which is used with 5-ALA. In the present study, we investigated the role of 5-ALA in the attenuation of acute renal IRI using a mouse model. Male Balb/c mice received 30 mg/kg 5-ALA with Fe 2ϩ 48, 24, and 2 h before IRI and were subsequently subjected to bilateral renal pedicle occlusion for 45 min. The endogenous CO concentration of the kidneys from the mice administered 5-ALA/Fe 2ϩ increased significantly, and the peak concentrations of serum creatinine and blood urea nitrogen decreased. 5-ALA/Fe 2ϩ treatments significantly decreased the tubular damage and number of apoptotic cells. IRIinduced renal thiobarbituric acid-reactive substance levels were also significantly decreased in the 5-ALA/Fe 2ϩ group. Furthermore, mRNA expression of HO-1, TNF-␣, and interferon-␥ was significantly increased after IRI. Levels of HO-1 were increased and levels of TNF-␣ and interferon-␥ were decreased in the 5-ALA/Fe 2ϩ -pretreated renal parenchyma after IRI. F4/80 staining showed reduced macrophage infiltration, and TUNEL staining revealed that there were fewer interstitial apoptotic cells. These findings suggest that 5-ALA/ Fe 2ϩ can protect the kidneys against IRI by reducing macrophage infiltration and decreasing renal cell apoptosis via the generation of CO.5-aminolevulinic acid; carbon monoxide; hemeoxygenase-1; kidney; ischemia-reperfusion injury; oxidative stress RENAL ISCHEMIA-REPERFUSION INJURY (IRI) is a complex pathophysiological process involving programmed cell death (PCD) and oxidant damage that leads to acute renal failure (AFR). The mortality rate of ARF remains between 50% and 70% among patients who receive intensive care who require dialysis and ranges between 25% and 100% in postoperative patients suffering from ARF. Renal IRI is unavoidable in renal transplantation and may lead to acute posttransplant tubular necrosis (21,24,49,55) and delayed graft function (27,47). Recent findings have indicated that carbon monoxide (CO), an endogenous byproduct of heme degradation through the heme oxygenase (HO) system, exerts cytoprotective effects by reducing the expression of proinflammatory mediators, preventing vascular constriction, decreasing platelet aggregation, and inhibiting apoptosis (41, 66). Subsequent studies have actively used exogenous CO to treat various experimental disease conditions. In the field of transplantation, CO has been shown to inhibit acute and chronic allograft rejection (37, 57) and the rejection of xenografts (53). Furthermore, studies in the area of renal disease have reported that CO-releasing molecules (CORMs) protect against the renal damage in ischemia-induced ARF in mice (63), cisplatin-induced nephrotoxicity in rats (60), and cold ischemia and reperfusion injury during kidney transplantation of both iso-and allografts in rats (5) and mice (55).5-Aminolevulinic acid (5-ALA), an intermediate in heme synthesis, is fundamental for aerobic energy metabolism. It is used as a photo sensitizer precursor for photodynamic diagnosis and photodynamic therapy to identify and kill tu...

In conclusion, we successfully generated a stable 5-Gene model, which could be utilized to predict prognosis of GC patients and would contribute to postoperational treatment and follow-up strategies.

Although several chemokines play key roles in the pathogenesis of acute lung injury (ALI), the roles of chemokine (C‐X‐C motif) ligand 16 (CXCL16) and its receptor C‐X‐C chemokine receptor type 6 (CXCR6) in ALI pathogenesis remain to be elucidated. The mRNA and protein expression of CXCL16 and CXCR6 was detected after lipopolysaccharide (LPS) stimulation with or without treatment with the nuclear factor‐κB (NF‐κB) inhibitor pyrrolidine dithiocarbamate (PDTC). Lung injury induced by LPS was evaluated in CXCR6 knockout mice. CXCL16 level was elevated in the serum of ALI patients (n = 20) compared with healthy controls (n = 30). CXCL16 treatment (50, 100, and 200 ng/mL) in 16HBE cells significantly decreased the epithelial barrier integrity and E‐cadherin expression, and increased CXCR6 expression, reactive oxygen species (ROS) production, and p38 phosphorylation. Knockdown of CXCR6 or treatment with the p38 inhibitor SB203580 abolished the effects of CXCL16. Moreover, treatment of 16HBE cells with LPS (5, 10, 20 and 50 μg/mL) significantly increased CXCL16 release as well as the mRNA and protein levels of CXCL16 and CXCR6. The effects of LPS treatment (20 μg/mL) were abolished by treatment with PDTC. The results of the luciferase assay further demonstrated that PDTC treatment markedly inhibited the activity of the CXCL16 promoter. In conclusion, CXCL16, whose transcription was enhanced by LPS, may be involved in ROS production, epithelial barrier dysfunction and E‐cadherin down‐regulation via p38 signalling, thus contributing to the pathogenesis of ALI. Importantly, CXCR6 knockout or inhibition of p38 signalling may protect mice from LPS‐induced lung injury by decreasing E‐cadherin expression.