sRAGE及RAGE在胃癌患者中的临床意义分析

目的探讨与分析血清可溶性晚期糖基化终末产物受体(sRAGE)及RAGE在胃癌患者中的临床意义。方法选择手术切除的78例胃癌患者(胃癌组)与78例胃良性肿瘤患者(良性组),采用免疫组化法检测RAGE表达水平,采用酶联免疫法检测sRAGE表达水平。结果胃癌组的sRAGE表达水平显著高于良性组(P<0.05)。胃癌组的RAGE表达阳性率为83.3%,显著高于良性组的20.5%(P<0.05)。在胃癌组中,sRAGE表达水平与临床分期、肿瘤直径、浆膜浸润、组织学分化程度等有显著相关性(P<0.05);logistic分析显示临床分期、肿瘤直径、浆膜浸润为影响患者RAGE表达阳性率的主要因素(P<0.05)。结论胃癌患者血液中sRAGE呈现高表达,组织中RAGE表达阳性率高,与患者的临床分期、肿瘤直径、浆膜浸润、组织学分化程度等显著相关。     

Endogenous secretory RAGE increases with improvements in body composition and is associated with markers of adipocyte health

Background and aims

The receptor for advanced glycation end products (RAGE) is implicated in obesogenesis. Conversely, soluble RAGE (sRAGE) competitively inhibits RAGE. Our aim was to determine the effects of weight-loss via alternate day fasting (ADF) on sRAGE isoforms and evaluate potential relationships with body composition.

Advanced glycation end products in the skin are enhanced in COPD

Background

Cigarette smoking is the main cause of chronic obstructive pulmonary disease (COPD) inducing oxidative stress and local tissue injury, resulting in pulmonary inflammation. Advanced glycation end products (AGEs) are produced by glycation and oxidation processes and their formation is accelerated in inflammatory conditions. In this study we assessed whether AGE accumulation in the skin is elevated in COPD and associates with disease severity.

Methods

202 mild-to-very-severe COPD patients and 83 old (40–75 years) and 110 young (18–40 years) healthy smokers and never-smokers were included. AGEs were measured by skin autofluorescence (SAF). Demographic variables, smoking habits, co-morbidities and lung function values were obtained.

Results

COPD patients (FEV₁ = 55% predicted) had significantly higher SAF values than old and young healthy controls: 2.5 vs. 1.8 and 1.2 (arbitrary units, p < 0.05). No differences in SAF values were found between GOLD stages I-IV (2.4, 2.3, 2.5, 2.5 respectively). Lower function (FEV₁/FVC, MEF₅₀/FVC, RV/TLC) and higher number of packyears were significantly associated with SAF (p < 0.05).

Conclusions

SAF is increased in mild-to-very severe COPD patients compared with healthy controls. Interestingly, SAF was not associated with disease severity as values were comparable between different GOLD stages (stage I-IV) of COPD. This may suggest that AGEs play a role in the induction phase of COPD in susceptible smokers. Future studies should further investigate the mechanisms underlying AGEs formation and accumulation in COPD.     

Changes in circulating levels of carboxymethyllysine,soluble receptor for advanced glycation end products (sRAGE), and inflammation markers in women during normal pregnancy

Abstract

Objective: To determine the circulating levels of insulin, Nε-carboxymethyllysine (CML), soluble receptor for advanced glycation end products (sRAGE), and markers of inflammation and oxidative stress (OS) in maternal and umbilical cord blood in a cohort of healthy women with normal pregnancy.

Methods: We conducted an observational longitudinal study in a group of women (n?=?31; age range 18–39 years) with healthy pregnancy starting at 30 weeks of gestation and finishing at the time of delivery. We collected weight and height in the participants and their neonates and calculated body mass index (BMI). Blood from each patient was collected at 30th week of pregnancy and at delivery when a sample of cord blood was also obtained. Glucose, lipid profile, CML, sRAGE, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), highly sensitivity C-reactive protein (hsPCR), and insulin were determined. The study was approved by the University of Guanajuato Institutional Ethics Committee.

Results: All pregnancies reached term (mean gestational time 38.9?±?0.83 weeks) and there were no maternal complications. Mean age was 27.6 years. Lipid profile values were higher in the group compared with our values in nonpregnant women. During pregnancy, levels of insulin increased (p?<?.0006), CML (p?<?.0001) and sRAGE (p?<?.01) decreased, levels of MDA did not change, while those of TNF-α and hsPCR tended to increase. In the neonates, we found lower levels of CML (p?<?.003), hsPCR (p?<?.004), and insulin (p?<?.004) and higher levels of sRAGE (p?<?.013) and TNF-α (p?<?.022) compared to their mothers at delivery. In the total group, we found association of CML of the mother at baseline with the CML (p?<?.0006) and MDA (p?<?.002) in neonates, while maternal sRAGE at the end of pregnancy was associated with CML (p?<?.004) of their neonates.

Conclusions: Our study confirms that normal pregnancy is accompanied by insulin resistance (IR) and significant increase in lipid profile, and demonstrates that circulating levels of CML and sRAGE decreased significantly at the end of pregnancy. The lack of association between the course of insulin levels and those of CML probably results from the predominant role of placental factors in the pathogenesis of IR in pregnancy. sRAGE levels in the neonates are markedly increased compared to their mothers suggesting a placental origin of this compound which may have a protective effect on the fetus since sRAGE restricts Advanced glycation end product (AGE) effects and may exert anti-inflammatory effects.     

Soy isoflavones attenuate oxidative stress and improve parameters related to aging and Alzheimer’s disease in C57BL/6J mice treated with d-galactose

d-galactose (DG)-induced aging in C57BL/6J (B6) mice (3–4 mo) was used to examine the effects of soy isoflavones (SIF). Mice were divided into six groups: corn oil control, DG treatment, DG + melatonin (1 mg/kg BW), and DG + low (0.1 mg/kg), median (0.5 mg/kg) or high (2.5 mg/kg) SIF. DG was administered (s.c., 0.3 mL of 1% solution/mouse) daily for 50 days, during which melatonin and SIF were given (p.o.) 5 d/wk. A 7th group of B6 mice (11 mo) served as natural aging (NA) control, which received neither DG nor other treatments. DG significantly increased: (1) thiobarbituric acid-reactive substances in serum and brain; (2) protein carbonyls in liver, kidney and brain; (3) soluble extracellular receptors for advanced glycation end products in serum; (4) expression of Bax and caspase-3 proteins in splenocytes; (5) protein expression of Aβ, presenilin-1 and β-site amyloid precursor protein cleaving enzyme-1 in brain. SIF significantly attenuated DG-induced changes, with high SIF completely reversing most of these changes. The DG treatment group and the NA group had similar changes in most of the parameters measured. Overall, this DG-mimetic aging study shows that SIF effectively attenuate oxidative damage and improve parameters related to aging and Alzheimer’s disease.