Correlation between soluble receptor for advanced glycation end products levels and coronary artery disease in postmenopausal nondiabetic women

BACKGROUND The established cardiovascular risk factors cannot explain the overall risk of coronary artery disease(CAD),especially in women.Therefore,there is a growing need for the assessment of novel biomarkers to identify women at risk.The receptor for advanced glycation end products(RAGE)and its interaction with the advanced glycation end product(AGE)ligand have been associated with atherogenesis.The soluble fraction of RAGE(sRAGE)antagonizes RAGE signaling and exerts an antiatherogenic effect.AIM The study aim was to explore the association between plasma levels of sRAGE and CAD in nondiabetic postmenopausal women.METHODS This case-control study included 110 nondiabetic postmenopausal women who were enrolled in two groups.Group I included 55 angiographically proven CAD subjects with>50%stenosis in at least one of the major coronary arteries and Group II included 55 healthy control women who did not have CAD or had<50%stenosis of the coronary arteries.Stenosis was confirmed by invasive angiography.Plasma sRAGE was determined by an enzyme-linked immunosorbent assay.RESULTS We observed significantly lower plasma sRAGE concentrations in subjects with CAD vs healthy controls(P<0.05).Univariate and multivariate logistic regression analysis also revealed a significant correlation between plasma sRAGE levels and CAD(P=0.01).Multivariate odds ratios for CAD revealed that subjects with sRAGE concentrations below 225 pg/mL(lowest quartile)had a 6-fold increase in CAD prevalence independent of other risk factors.CONCLUSION Our findings indicated that low sRAGE levels were independently associated with CAD in nondiabetic postmenopausal women.Risk assessment of CAD in postmenopausal women can be improved by including sRAGE along with other risk factors.

Receptor for advanced glycation end-products axis and coronavirus disease 2019 in inflammatory bowel diseases:A dangerous liaison?

Compelling evidence supports the crucial role of the receptor for advanced glycation end-products(RAGE)axis activation in many clinical entities.Since the beginning of the coronavirus disease 2019 pandemic,there is an increasing concern about the risk and handling of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in inflammatory gastrointestinal disorders,such as inflammatory bowel diseases(IBD).However,clinical data raised during pandemic suggests that IBD patients do not have an increased risk of contracting SARS-CoV-2 infection or develop a more severe course of infection.In the present review,we intend to highlight how two potentially important contributors to the inflammatory response to SARS-CoV-2 infection in IBD patients,the RAGE axis activation as well as the cross-talk with the renin-angiotensin system,are dampened by the high expression of soluble forms of both RAGE and the angiotensin-converting enzyme(ACE)2.The soluble form of RAGE functions as a decoy for its ligands,and soluble ACE2 seems to be an additionally attenuating contributor to RAGE axis activation,particularly by avoiding the transactivation of the RAGE axis that can be produced by the virus-mediated imbalance of the ACE/angiotensin II/angiotensin II receptor type 1 pathway.

Increased expression of receptor for advanced glycation end-products worsens focal brain ischemia in diabetic rats

A rat model of diabetes mellitus was induced by a high fat diet, followed by focal brain ischemia induced using the thread method after 0.5 month. Immunohistochemistry showed that expression of receptor for advanced glycation end-products was higher in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Western blot assay revealed increased phosphorylated c-Jun N-terminal kinase expression, and unchanged phosphorylated extracellular signal-regulated protein kinase protein expression in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Additionally, phosphorylated p38 mitogen-activated protein kinase protein was not detected in any rats in the two groups. Severity of limb hemiplegia was worse in diabetic rats with brain ischemia compared with ischemia alone rats. The results suggest that increased expression of receptor for advanced glycation end-products can further activate the c-Jun N-terminal kinase pathway in mitogen-activated protein kinase, thereby worsening brain injury associated with focal brain ischemia in diabetic rats.

Receptor of advanced glycation end-products axis and gallbladder cancer:A forgotten connection that we should reconsider

Compelling evidence derived from clinical and experimental research has demonstrated the crucial contribution of chronic inflammation in the development of neoplasms,including gallbladder cancer.In this regard,data derived from clinical and experimental studies have demonstrated that the receptor of advanced glycation end-products(RAGE)/AGEs axis plays an important role in the onset of a crucial and long-lasting inflammatory milieu,thus supporting tumor growth and development.AGEs are formed in biological systems or foods,and food-derived AGEs,also known as dietary AGEs are known to contribute to the systemic pool of AGEs.Once they bind to RAGE,the activation of multiple and crucial signaling pathways are triggered,thus favoring the secretion of several proinflammatory cytokines also involved in the promotion of gallbladder cancer invasion and migration.In the present review,we aimed to highlight the relevance of the association between high dietary AGEs intakes and high risk for gallbladder cancer,and emerging data supporting that dietary intervention to reduce gallbladder cancer risk is a very attractive approach that deserves much more research efforts.

Contributions of the receptor for advanced glycation end products axis activation in gastric cancer

Compelling shreds of evidence derived from both clinical and experimental research have demonstrated the crucial contribution of receptor for advanced glycation end products(RAGE)axis activation in the development of neoplasms,including gastric cancer(GC).This new actor in tumor biology plays an important role in the onset of a crucial and long-lasting inflammatory milieu,not only by supporting phenotypic changes favoring growth and dissemination of tumor cells,but also by functioning as a pattern-recognition receptor in the inflammatory response to Helicobacter pylori infection.In the present review,we aim to highlight how the overexpression and activation of the RAGE axis contributes to the proliferation and survival of GC cells as and their acquisition of more invasive phenotypes that promote dissemination and metastasis.Finally,the contribution of some single nucleotide polymorphisms in the RAGE gene as susceptibility or poor prognosis factors is also discussed.

Intra-coronary administration of soluble receptor for advanced glycation end-products attenuates cardiac remodeling with decreased myocardial transforming growth factor-pl expression and fibrosis in minipigs with ischemia-reperfusion injury

Background The cardioprotective effects of soluble receptor for advanced glycation end-products （sRAGE） have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion （I/R） injury. Methods Ten male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE （sRAGE group, n=5） or saline （control group, n=5）. Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor （TGF）-β1 was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining. Results As compared with the baseline values in the control animals, left ventricular end-diastolic volume （from （19.5±5.1） to （32.3±5.6） ml, P 〈0.05） and end-systolic volume （from （8.3±3.2） to （15.2±4.1） ml, P 〈0.05） were significantly increased, whereas ejection fraction was decreased （from （61.6±13.3）% to （50.2±11.9）%, P 〈0.05）. No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-β1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group （both P 〈0.01）. Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals （P〈0.05）. Conclusion Intra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-β1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.

Intrafollicular Soluble RAGE Benefits Embryo Development and Predicts Clinical Pregnancy in Infertile Patients of Advanced Maternal Age Undergoing In Vitro Fertilization

Soluble receptor for advanced glycation end products（s RAGE） can decoy the toxic AGEs and is considered to be a protective factor.This study aimed to evaluate the correlation between intrafollicular s RAGE levels and clinical outcomes in infertile women of young or advanced maternal age（AMA） undergoing in vitro fertilization（IVF）.A total of 62 young women and 62 AMA women who would undergo IVF were included in this prospective study.The intrafollicular s RAGE concentration was measured to determine its association with the number of retrieved oocytes,fertilized oocytes,high-quality embryos or achievement of clinical pregnancy in young and AMA women,respectively.Besides,correlations between sR AGE and age or follicle-stimulating hormone（FSH） were examined.We found that the intrafollicular s RAGE levels were higher in young patients than those in AMA patients,suggesting that the s RAGE levels were inversely correlated with age.In young patients,sR AGE showed no correlation with the number of retrieved oocytes,fertilized oocytes,high-quality embryos or achievement of clinical pregnancy.But it was found that AMA patients with more retrieved oocytes,fertilized oocytes and high-quality embryos demonstrated higher sR AGE levels,which were a prognostic factor for getting clinical pregnancy independent of age or FSH level.In conclusion,the s RAGE levels decrease with age.Elevated intrafollicular s RAGE levels indicate good follicular growth,fertilization and embryonic development,and successful clinical pregnancy in AMA women,while in young women,the role of s RAGE may not be so predominant.

血清S100钙结合蛋白A12、可溶性晚期糖基化终末产物受体水平与维持性血液透析患者骨质疏松的相关性分析

目的探讨维持性血液透析(MHD)患者血清S100钙结合蛋白A12(S100A12)、可溶性晚期糖基化终末产物受体(sRAGE)的水平变化及与骨质疏松的关系。方法选取2020年1月~2022年6月在本院血透室治疗的MHD患者110例,根据T值将其分为骨质疏松组(42例,T值≤-2.5 g/cm2)及非骨质疏松组(68例,T值>-2.5 g/cm2),同期选取在本院健康体检者50例为对照组。收集所有受试者的一般资料(性别、年龄、BMI、透析龄)及临床资料并进行组间比较。相关性分析采用Pearson相关分析。采用受试者工作特征(ROC)曲线评估血清sRAGE和S100A12水平对MHD患者骨质疏松的预测价值。采用多重线性回归分析探讨MHD患者发生骨质疏松的影响因素。结果与对照组相比,非骨质疏松组与骨质疏松组患者血钙、血磷、骨密度、sRAGE水平均降低,全段甲状旁腺激素(iPTH)、尿素氮(BUN)、血肌酐(SCr)、白蛋白(Alb)、S100A12水平均升高(P<0.05)。与非骨质疏松组相比,骨质疏松组患者血清iPTH、S100A12水平均升高,血磷、骨密度、sRAGE水平均降低(P<0.05)。Pearson相关分析结果显示,MHD患者血清sRAGE与S100A12表达呈负相关;血清sRAGE与血磷、骨密度均呈正相关,与iPTH呈负相关;血清S100A12与血磷、骨密度均呈负相关,与iPTH呈正相关(P<0.05)。ROC曲线分析结果显示,血清S100A12、sRAGE联合预测MHD患者骨质疏松的ROC曲线下面积(AUC)、特异度均高于二者单独预测。多重线性回归分析结果显示,MHD患者S100A12、sRAGE、iPTH均与骨质疏松发生有关(P<0.05)。结论MHD患者骨质疏松发生与sRAGE、S100A12密切相关,联合检测二者可作为诊断MHD患者骨质疏松发生的指标。

CML、sRAGE、esRAGE对冠心病动脉粥样硬化的诊断价值

目的探讨ε-羧甲基赖氨酸(CML)、可溶性晚期糖基化终产物受体(sRAGE)、内源性可溶性晚期糖基化终产物受体(esRAGE)对冠心病动脉粥样硬化的诊断价值。方法2020年6月至2022年12月,于新疆维吾尔自治区人民医院选取冠心病患者100例作为观察组。同时选取100例在我院体检的正常人作为对照组。比较两组ε-羧甲基赖氨酸(CML)、可溶性晚期糖基化终产物受体(sRAGE)和内源性分泌性晚期糖基化终产物受体(esRAGE)水平。应用受试者操作者特征(ROC)曲线评价CML、sRAGE、esRAGE的诊断水平,并联合检测冠心病动脉粥样硬化。结果与对照组相比,观察组血清CML及sRAGE水平明显升高,而esRAGE水平呈下降趋势。血清CML、sRAGE和esRAGE可准确诊断冠心病动脉粥样硬化,联合检测灵敏度(90.91%)、特异性(68.66%)、准确性(76.00%)、阳性预测值(58.82%)、阴性预测值(93.88%)、ROC曲线下面积(AUC)(0.922)较高。结论CML、sRAGE、esRAGE与冠心病动脉粥样硬化有关,有利于临床诊断和治疗。

结肠癌病人血清S100钙结合蛋白A12、可溶性晚期糖基化终产物受体水平与肠道菌群失调及化疗效果的关系

目的探讨结肠癌病人血清S100钙结合蛋白A12(S100A12)、可溶性晚期糖基化终产物受体(sRAGE)水平与肠道菌群失调及化疗效果的相关性。方法选择2020年12月至2021年12月黄河水利委员会黄河中心医院收治的116例中、晚期结肠癌病人作为结肠癌组,另选取在该院同期健康体检人员120例作为对照组。采用酶联免疫吸附测定(ELISA)检测血清S100A12、sRAGE水平,检测病人肠道菌群,并对病人化疗后进行随访,Pearson法分析结肠癌病人血清S100A12、sRAGE水平与菌群失调相关性,受试者操作特征曲线(ROC曲线)分析化疗前血清S100A12、sRAGE水平对结肠癌化疗效果的诊断价值。结果与对照组比较,结肠癌组病人化疗前血清S100A12、sRAGE水平显著升高(P<0.05)。与化疗前菌群正常组[(265.34±45.78)μg/L、(381.54±36.75)ng/L]比较,菌群失调Ⅰ度组[(301.52±56.95)μg/L、(440.63±48.71)ng/L]、菌群失调Ⅱ度组[(339.29±52.35)μg/L、(432.75±49.20)ng/L]病人血清S100A12、sRAGE水平显著升高(P<0.05);与菌群失调Ⅰ度组比较,菌群失调Ⅱ度组病人血清S100A12、sRAGE水平显著升高(P<0.05)。相关性分析显示,结肠癌病人血清S100A12、sRAGE水平与大肠杆菌、粪肠球菌数量呈正相关(P<0.05),与双歧杆菌、乳酸杆菌数量呈负相关(P<0.05)。与化疗前比较,结肠癌病人化疗后血清S100A12、sRAGE水平显著降低(P<0.05);与化疗缓解组[(272.33±55.36)μg/L、(403.24±40.54)ng/L]比较,化疗无效组[(330.09±42.64)μg/L、(482.85±43.61)ng/L]病人化疗前血清S100A12、sRAGE水平显著较高(P<0.05)。血清S100A12、sRAGE联合诊断结肠癌化疗无效的曲线下面积(AUC)为0.91[95%CI:(0.84,0.96),P<0.001],灵敏度为86.05%,特异度为80.82%。结论结肠癌病人血清S100A12、sRAGE升高,与肠道菌群失调及化疗效果有关,对化疗疗效评估与预后评价有一定指导意义。

血清D-二聚体和sRAGE水平对老年冠心病患者介入治疗后短期不良预后的预测价值

[目的]探究D-二聚体和可溶性晚期糖基化终末产物受体(sRAGE)水平对老年冠心病患者经皮冠状动脉介入治疗(PCI)后短期不良预后的预测价值。[方法]收集2019年4月-2020年6月在黄冈市中心医院首次诊断为冠心病的316例老年患者的临床资料,根据随访期间患者是否发生主要不良心血管事件(MACE)将其分为MACE组(n=52)和非MACE组(n=264),采用单因素分析和多因素Logistic回归分析患者术后发生MACE的独立影响因素,依据患者预后的独立影响因素建立列线图预测模型并进行验证。通过曲线拟合和阈值效应分析确定D-二聚体和sRAGE水平的阈值效应,并通过Kaplan-Meier曲线评估D-二聚体和sRAGE水平对MACE发生的影响。[结果]术后一年期间,纳入的316例老年冠心病患者中有52例(16.46%)发生MACE。MACE组患者的体质指数(BMI)、高血压占比、糖尿病占比、GRACE评分、支架数目、载脂蛋白(Apo)B、ApoB/ApoA、低密度脂蛋白胆固醇(LDLC)、脂蛋白(a)[Lp(a)]以及D-二聚体水平均高于非MACE组,sRAGE水平低于非MACE组,差异均具有统计学意义(P<0.05)。多因素Logistic回归分析表明,高GRACE评分、高Lp(a)及高D-二聚体水平为老年冠心病患者PCI术后发生MACE的独立危险因素,高sRAGE水平为保护因素(P<0.05)。曲线拟合发现,随着D-二聚体水平的升高以及sRAGE水平的降低,患者术后发生MACE的概率呈上升趋势。Kaplan-Meier曲线显示,较高D-二聚体水平的患者MACE的发生概率显著高于低D-二聚体水平的患者(P<0.001),较低sRAGE水平的患者MACE的发生概率显著高于高sRAGE水平的患者(P<0.001)。依据预后独立影响因素构建列线图模型,其一致性指数为0.796(95%CI:0.723~0.834),ROC曲线AUC为0.851(95%CI:0.806~0.892),具有较好的区分度。[结论]高D-二聚体及低sRAGE水平是老年冠心病患者PCI术后发生MACE的重要危险因素,且对术后短期不良预后具有较高的预测价值。

可溶性晚期糖基化终产物受体、白细胞介素-36γ在桥本甲状腺炎患者血清中的表达及意义

目的探讨可溶性晚期糖基化终产物受体(sRAGE)、白细胞介素-36γ(IL-36γ)在桥本甲状腺炎(HT)患者血清中的表达及其临床意义。方法选取180例疑似HT人员作为研究对象,根据最终诊断结果分为HT组137例和非HT组43例。依据血清免疫球蛋白G4(IgG4)水平,将HT组患者进一步分为IgG4相关性HT组(IgG4≥135 mg/dL)和非IgG4相关性HT组(IgG4<135 mg/dL)。采用酶联免疫吸附试验(ELISA)法检测所有研究对象的血清sRAGE、IL-36γ水平;绘制受试者工作特征(ROC)曲线,分析血清sRAGE、IL-36γ水平对HT及其IgG4表型的诊断价值。结果HT组患者血清sRAGE水平低于非HT组,血清IL-36γ水平高于非HT组,差异有统计学意义(P<0.001);IgG4相关性HT组患者血清sRAGE水平低于非IgG4相关性HT组,血清IL-36γ水平高于非IgG4相关性HT组,差异有统计学意义(P<0.001)。ROC曲线分析结果显示,血清sRAGE、IL-36γ联合诊断HT的曲线下面积(AUC)为0.900(95%CI:0.846~0.939),诊断效能显著高于两者单独诊断(P<0.05);血清sRAGE、IL-36γ联合诊断HT患者IgG4表型的AUC为0.897(95%CI:0.934~0.943),诊断效能显著高于两者单独诊断(P<0.05)。结论HT患者血清sRAGE水平显著降低,血清IL-36γ水平显著升高,联合检测血清sRAGE、IL-36γ水平可有效诊断HT并评估IgG4表型。

High glucose reduces Nrf2-dependent cRAGE release and enhances inflammasome-dependent IL-1βproduction in monocytes:the modulatory effects of EGCG

Soluble receptor for advanced glycation end products(sRAGE)acts as a decoy sequestering of RAGE ligands,thus preventing the activation of the ligand-RAGE axis linking human diseases.However,the molecular mechanisms underlying sRAGE remain unclear.In this study,THP-1 monocytes were cultured in normal glucose(NG,5.5 mmol/L)and high glucose(HG,15 mmol/L)to investigate the effects of diabetesrelevant glucose concentrations on sRAGE and interleukin-1β(IL-1β)secretion.The modulatory effects of epigallocatechin gallate(EGCG)in response to HG challenge were also evaluated.HG enhanced intracellular reactive oxygen species(ROS)generation and RAGE expression.The secretion of sRAGE,including esRAGE and cRAGE,was reduced under HG conditions,together with the downregulation of a disintegrin and metallopeptidase 10(ADAM10)and nuclear factor erythroid 2-related factor 2(Nrf2)nuclear translocation.Mechanistically,the HG effects were counteracted by siRAGE and exacerbated by siNrf2.Chromatin immunoprecipitation results showed that Nrf2 binding to the ADAM10 promoter and HG interfered with this binding.Our data reinforce the notion that RAGE and Nrf2 might be sRAGE-regulating factors.Under HG conditions,the treatment of EGCG reduced ROS generation and RAGE activation.EGCG-stimulated cRAGE release was likely caused by the upregulation of the Nrf2-ADAM10 pathway.EGCG inhibited HG-mediated NLRP3 inflammasome activation at least partly by stimulating sRAGE,thereby reducing IL-1βrelease.

血清高迁移率族蛋白B1、可溶性晚期糖基化终产物受体水平对急性失代偿性心力衰竭预后有评估价值

目的:探讨血清高迁移率族蛋白B1(HMGB1)、可溶性晚期糖基化终产物受体(sRAGE)水平对急性失代偿性心力衰竭(ADHF)患者预后的评估价值。方法:选取190例ADHF患者为研究组,另选取191例健康者为对照组,根据1年随访期是否死亡,将ADHF患者分为预后不良组(58例)和预后良好组(132例);采用酶联免疫吸附法(ELISA)检测血清HMGB1、sRAGE水平;采用Pearson法分析血清HMGB1、sRAGE水平与心功能指标及实验室指标的相关性;采用受试者工作特征(ROC)曲线分析HMGB1、sRAGE及血浆N端脑钠肽前体(NT-proBNP)对ADHF患者预后的评估价值;采用多因素Logistic回归分析影响ADHF患者预后的因素。结果:与对照组比较,研究组患者血清HMGB1、sRAGE水平更高(P均<0.05);预后良好组与不良组血清HMGB1、sRAGE水平、纽约心脏病协会(NYHA)分级、左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、左室射血分数(LVEF)、NT-proBNP、血清肌钙蛋白I(cTnI)、住院时间比较,差异有统计学意义(P均<0.05)。经Pearson法分析,ADHF患者血清HMGB1、sRAGE分别与LVEDD、LVESD、NT-proBNP、cTnl呈正相关,与LVEF呈负相关(P均<0.05),血清HMGB1与sRAGE呈正相关(P<0.05)。ROC曲线分析显示,HMGB1、sRAGE、NT-proBNP对ADHF患者预后不良评估价值均较高,AUC分别为0.869、0.852、0.844,最佳截断值分别为32.91 g/L、296.46 ng/L、3809.77 ng/L时,灵敏度分别为79.3%、82.8%、82.8%,特异性分别为83.3%、74.2%、79.5%。多因素logistic回归分析表明,NYHA分级、LVEF、NT-proBNP、HMGB1及sRAGE是ADHF患者预后的独立危险因素(P均<0.05)。结论:血清HMGB1、sRAGE表达与ADHF的发生及预后有关,可作为ADHF患者预后的评估指标。

毛细支气管炎患儿血清sRAGE、YKL-40与Th17_Treg失衡对喘息复发的预测价值研究

目的 探讨毛细支气管炎患儿可溶性晚期糖基化终末产物受体(sRAGE)、壳多糖酶3样蛋白1(YKL-40)与辅助性T细胞17(Th17)/调节性T细胞(Treg)失衡的关系及对出院后发生反复喘息的预测价值。方法 选取我院收治的197例毛细支气管炎患儿为毛细支气管炎组,另选取100名体检健康婴幼儿为对照组。检测两组sRAGE、YKL-40水平,并分析其与Th17、Treg、Th17/Treg的相关性。出院后随访3年,根据患儿是否发生反复喘息分为反复喘息组和非反复喘息组。分析患儿出院后反复喘息影响因素及sRAGE、YKL-40的预测价值。结果 与对照组比较,毛细支气管炎组sRAGE和Treg降低,YKL-40和Th17、Th17/Treg升高(P<0.05)。毛细支气管炎患儿sRAGE与Th17、Th17/Treg呈负相关,与Treg呈正相关;YKL-40则反之(P<0.05)。母乳喂养和sRAGE升高为毛细支气管炎患儿出院后反复喘息的保护因素,哮喘家族史和免疫球蛋白E(IgE)、Th17/Treg、YKL-40升高为危险因素(P<0.05)。sRAGE、YKL-40联合检测预测毛细支气管炎患儿出院后反复喘息的曲线下面积(AUC)为0.897(0.846~0.936),大于sRAGE、YKL-40单独检测预测的0.799(0.736~0.853)、0.795(0.732~0.849)(Z=3.938、3.839,P均<0.001)。结论 毛细支气管炎患儿sRAGE降低、YKL-40升高与Th17/Treg失衡及出院后反复喘息有关,二者联合检测对出院后反复喘息具有较高的预测价值。

N-acetylserotonin alleviates retinal ischemia-reperfusion injury via HMGB1/RAGE/NF-κB pathway in rats

AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling pathway.METHODS:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the eye.Eighty male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)counting.The expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot analysis.The expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR rats.With NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein expression.Additionally,NAS exhibited an anti-inflammatory effect by reducing IL-1βexpression.The inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR rats.CONCLUSION:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.

血清CC16、sRAGE水平与ARDS患者疾病转归的相关性及预测价值研究

目的 探讨血清Clara细胞分泌蛋白16(CC16)、可溶性晚期糖基化终产物受体(sRAGE)水平变化与急性呼吸窘迫综合征(ARDS)患者疾病转归的相关性及预测价值。方法 选取2021年1月至2023年1月灵宝市第二人民医院收治的127例ARDS患者为研究对象,根据ARDS严重程度将患者分为轻度组(39例)、中度组(52例)和重度组(36例)。比较不同严重程度患者及不同疾病转归患者血清CC16、sRAGE水平、氧合指数(PaO_(2)/FiO_(2))、急性生理学及慢性健康状况Ⅱ(APACHEⅡ)评分、序贯器官衰竭评估(SOFA)评分,分析血清CC16、sRAGE水平与PaO_(2)/FiO_(2)、APACHEⅡ评分、SOFA评分及疾病转归的相关性。采用logistic回归分析ARDS患者病死的危险因素,受试者工作特征(ROC)曲线分析血清CC16、sRAGE水平及二者联合检测对ARDS患者病死的预测价值。结果 ARDS不同程度患者入院时血清CC16、sRAGE水平及APACHEⅡ、SOFA评分比较:轻度组<中度组<重度组,PaO_(2)/FiO_(2)比较:轻度组>中度组>重度组,差异均有统计学意义(P<0.05);病死患者入院时血清CC16、sRAGE水平及APACHEⅡ、SOFA评分均高于生存患者,而PaO_(2)/FiO_(2)低于生存患者,差异均有统计学意义(P<0.05);患者入院时血清CC16、sRAGE水平与PaO_(2)/FiO_(2)均呈负相关(P<0.05),与APACHEⅡ、SOFA评分及疾病转归均呈正相关(P<0.05);入院时血清CC16、sRAGE水平为ARDS患者病死的危险因素,且两指标联合预测ARDS患者病死的ROC曲线下面积大于各单项指标(P<0.05)。结论 ARDS患者血清CC16、sRAGE表达上调,其水平与疾病转归密切相关,二者联合检测可作为临床早期预测转归情况的有效指标。

结核性脑膜炎患者血清sVCAM-1、sRAGE水平与病情严重程度及预后的关系

目的探讨血清可溶性血管细胞黏附分子1(sVCAM-1)和可溶性晚期糖基化终末产物受体(sRAGE)的表达与结核性脑膜炎(TBM)患者病情严重程度及预后的关系。方法选取2020年9月至2023年5月湖北省宜昌市第三人民医院收治的157例TBM患者为研究组,另外选取同期体检的151例健康者为对照组。根据入院时TBM分期将患者分为Ⅰ期组、Ⅱ期组和Ⅲ期组,根据TBM患者出院时改良Rankin量表(mRS)分为预后良好组和预后不良组。采用酶联免疫吸附试验(ELISA)检测血清sVCAM-1和sRAGE水平;采用多因素Logistic回归分析TBM患者预后的影响因素;采用受试者工作特征(ROC)曲线分析血清sVCAM-1和sRAGE对TBM患者预后的预测价值。结果与对照组比较,研究组血清sVCAM-1和sRAGE水平均明显升高,差异均有统计学意义(t=23.819、25.965,P<0.05)。Ⅰ、Ⅱ、Ⅲ期组分别为34、76、47例。Ⅲ期组血清sVCAM-1和sRAGE水平高于Ⅱ期组、Ⅰ期组,且Ⅱ期组高于Ⅰ期组,差异均有统计学意义(P<0.05)。预后良好组、预后不良组分别为108、49例。与预后良好组比较,预后不良组血清sVCAM-1和sRAGE水平升高,以及TBM分期为Ⅲ期、有意识障碍和有外周神经功能障碍的患者比例明显升高,差异有统计学意义(t/χ^(2)=-6.123、-8.879、12.316、8.584、9.390,P<0.05)。多因素Logistic回归分析结果显示,血清sVCAM-1、sRAGE水平升高及TBM分期为Ⅲ期、有意识障碍、有外周神经功能障碍均是TBM患者预后不良的独立危险因素(OR=1.458、1.523、2.673、2.157、3.714,P<0.05)。ROC曲线分析结果显示,血清sVCAM-1水平预测TBM患者预后不良的曲线下面积(AUC)为0.831(95%CI:0.763~0.886)、灵敏度为69.39%,血清sRAGE水平预测TBM患者预后不良的AUC为0.844(95%CI:0.778~0.897)、灵敏度为71.43%,血清sVCAM-1和sRAGE水平联合检测预测TBM患者预后不良的AUC(0.914)明显大于两项单独预测的AUC(Z=2.789,P=0.005;Z=2.782,P=0.005)。结论sVCAM-1和sRAGE水平在TBM患者血清中升高,且与患者病情严重程度和预后有关,血清sVCAM-1和sRAGE水平联合检测对TBM患者预后不良具有较高的预测价值。

血清DKK1、sRAGE、hCAP-18对急性淋巴细胞白血病患儿的诊断和预后不良的预测价值

目的 探讨血清Dickkopf相关蛋白1(DKK1)、可溶性晚期糖基化终末产物受体(sRAGE)、人类阳离子抗菌蛋白-18(hCAP-18)对急性淋巴细胞白血病患儿的诊断和预后不良的预测价值。方法 选取2020年4月至2022年4月南京鼓楼医院集团宿迁医院收治的84例急性淋巴细胞白血病患儿作为研究组,包括标危28例、中危36例、高危20例。另选取同期在南京鼓楼医院集团宿迁医院体检的84例健康儿童作为对照组。收集所有研究对象的临床资料。采用酶联免疫吸附试验检测所有研究对象血清DKK1、sRAGE、hCAP-18水平。对研究组患儿进行为期1年的随访,并按随访结果分为预后不良组和预后良好组。绘制受试者工作特征(ROC)曲线分析血清DKK1、sRAGE、hCAP-18在急性淋巴细胞白血病患儿诊断和预后不良的预测价值。采用多因素Logistic回归分析影响急性淋巴细胞白血病发生的因素。结果 与对照组相比,研究组患儿白细胞计数(WBC)、DKK1水平显著升高,sRAGE、hCAP-18水平显著降低,差异均有统计学意义(P<0.05)。与研究组标危患儿相比,中危和高危患儿血清DKK1水平显著升高,sRAGE、hCAP-18水平显著降低,差异均有统计学意义(P<0.05);与中危患儿相比,高危患儿血清DKK1水平显著升高,sRAGE、hCAP-18水平显著降低,差异均有统计学意义(P<0.05)。血清DKK1、sRAGE、hCAP-18联合诊断急性淋巴细胞白血病的曲线下面积(AUC)显著高于血清DKK1、sRAGE、hCAP-18单独诊断的AUC(Z=2.820,P=0.005;Z=5.170,P<0.001;Z=5.272,P<0.001)。多因素Logistic回归分析结果显示,血清WBC、DKK1、sRAGE、hCAP-18是急性淋巴细胞白血病发生的影响因素(P<0.05)。随访1年后,26例患儿纳入预后不良组,58例患儿纳入预后良好组。与预后良好组相比,预后不良组患儿血清DKK1水平显著升高,sRAGE、hCAP-18水平显著降低,差异均有统计学意义(P<0.05)。与预后不良组中危患儿相比,高危患儿DKK1水平显著升高,sRAGE、hCAP-18水平显著降低,差异均有统计学意义(P<0.05)。血清DKK1、sRAGE、hCAP-18联合预测急性淋巴细胞白血病患儿预后不良的AUC明显高于血清DKK1、sRAGE、hCAP-18单独预测的AUC(Z=2.312,P=0.021;Z=3.160,P=0.002;Z=2.926,P=0.003)。结论 急性淋巴细胞白血病患儿血清DKK1高表达,sRAGE、hCAP-18低表达,且三者联合检测对急性淋巴细胞白血病具有一定的诊断和预后预测价值。

血清sRAGE联合ESM-1对重症急性胰腺炎合并应激性高血糖患者预后的预测价值研究

目的 探讨血清可溶性晚期糖基化终末产物受体(soluble receptor for advanced glycation end products,sRAGE)联合内皮细胞特异性分子-1(endothelial cell specific molecules-1,ESM-1)对重症急性胰腺炎(severe acute pancreatitis,SAP)合并应激性高血糖患者预后的预测价值。方法 选取2021年7月至2023年1月临汾市中心医院重症医学科的SAP合并应激性高血糖患者105例,根据患者的预后(对症治疗后28 d生存情况)分为死亡组(39例)和存活组(66例)。分析SAP合并应激性高血糖患者预后的影响因素及血清sRAGE联合ESM-1对患者预后的预测价值。结果 105例患者中男61例、女44例;年龄22~69岁,平均(47.6±8.9)岁。多因素logistic回归分析结果显示,多个器官功能障碍(OR=4.845,95%CI:2.166~8.130,P=0.030)、急性生理和慢性健康评分Ⅱ得分越高(OR=1.872,95%CI:1.207~2.902,P=0.005)、24 h随机空腹血糖越高(OR=1.381,95%CI:1.094~1.743,P=0.007)、sRAGE水平越高(OR=1.017,95%CI:1.007~1.027,P=0.001)、ESM-1水平越高(OR=1.074,95%CI:1.027~1.123,P=0.002)的SAP合并应激性高血糖患者更容易死亡。ROC曲线分析结果显示,血清sRAGE联合ESM-1检测预测SAP合并应激性高血糖患者死亡的AUC为0.882(95%CI:0.804~0.936,P<0.001),血清sRAGE和ESM-1单独预测的AUC分别为0.784(95%CI:0.693~0.859,P<0.001)和0.780(95%CI:0.689~0.855,P<0.001)。结论 SAP合并应激性高血糖患者的血清sRAGE、ESM-1浓度升高与不良预后有关,血清sRAGE联合ESM-1检测对SAP合并应激性高血糖患者预后的预测价值较高。