The potential use of urinary transferrin,urinary adiponectin,urinary Retinol Binding Protein,and serum zinc alpha 2 glycoprotein levels as novel biomarkers for early diagnosis of diabetic nephropathy: A case-control study

Background and aimsThe level of albuminuria is used to evaluate diabetic nephropathy (DN). However, to detect or predict the early stages of DN, better biomarkers are needed.MethodsThis study is a case-control observational study. 80 Egyptians participated in the study: 60 patients with type 2 diabetes mellitus (T2DM) were divided into three groups (20 patients each), and 20 healthy subjects with matched age and gender were used as controls. Demographic and laboratory data were analyzed. An enzyme-linked immunosorbent assay was used to determine the levels of four biomarkers of DN; urinary adiponectin (ADP), urinary transferrin, serum Zinc Alpha 2 Glycoprotein (ZAG), and urinary Retinol Binding Protein (RBP).ResultsThe levels of DN biomarkers urinary ADP, transferrin, RBP, and serum, ZAG were significantly higher in patients with T2DM than in controls. The ROC curve of the validity of the simultaneous use of all four biomarkers in predicting albuminuria indicates a sensitivity of 90% and a specificity of 90%. The Area Under the Curve (AUC) was 0.948, the 95% confidence interval was 0.998–0.897, and the p-value was 0.001.ConclusionsIn patients with T2DM, urine adiponectin, transferrin, RBP, and serum ZAG concentration may be useful biomarkers in the early diagnosis of DN. A further longitudinal prospective study is required to explore the potential utility of these biomarkers.     

锌α2糖脂蛋白通过调节ATP水平影响大肠癌HT-29细胞的侵袭能力

目的:锌α2糖脂蛋白(zinc-alpha-2-glycoprotein 1,ZAG)是新近发现的具有复杂功能的蛋白,ZAG参与受精?脂代谢及免疫调节等多种细胞生物学行为,本研究探讨ZAG在大肠癌演进过程中的作用?方法:本研究构建ZAG干扰质粒,并转染入HT-29结肠癌细胞株,免疫印迹与逆转录聚合酶链式反应(RT-PCR)方法检测转染前后ZAG表达的变化;检测转染前后细胞三磷酸腺苷(adenosine triphosphate,ATP)含量的变化,以了解ZAG对细胞代谢的影响;利用小室实验检测转染前后HT-29细胞侵袭能力的变化?结果:ZAG干扰质粒成功转染入HT-29细胞并筛选出稳定转染细胞株;转染后的HT-29细胞ATP水平上调,且转染后的HT-29侵袭能力增强?结论:研究结果提示ZAG可能通过调节ATP水平增强大肠癌HT-29细胞的侵袭能力,为大肠癌治疗提供了有价值的新靶点?     

锌α2糖蛋白对肝癌HepG2细胞增殖与侵袭能力的影响

目的：锌α2糖蛋白（ZAG）是一种具有复杂功能的蛋白。本研究探讨ZAG对肝脏肿瘤HepG2细胞增殖及侵袭能力的影响及其作用机理。方法：构建ZAG干扰质粒,并转染入HepG2肝癌细胞株,采用Western blot方法检测转染前后ZAG表达的变化;利用MTT和平板克隆实验检测ZAG对细胞增殖的影响,利用Transwell小室实验检测转染前后HepG2细胞侵袭能力的变化,同时检测转染前后细胞ATP含量的变化,以了解ZAG对细胞代谢的影响。结果与结论：ZAG干扰质粒成功转染入HepG2细胞并筛选出ZAG下调的稳定细胞株;转染后的HepG2细胞增殖能力、侵袭能力均有显著提高,同时ATP水平上调,肿瘤细胞恶性更强。     

Zinc-α2-Glycoprotein Expression in Adipose Tissue of Obese Postmenopausal Women before and after Weight Loss and Exercise + Weight Loss

Objective

Zinc-Alpha 2-Glycoprotein (ZAG) has recently been implicated in the regulation of adipose tissue metabolism due to its negative association with obesity and insulin resistance. The purpose of this study is to investigate the relationships between adipose tissue ZAG expression and central obesity, and the effects of six-months of weight loss (WL) or aerobic exercise + weight loss (AEX + WL) on ZAG expression.

Design and Methods

A six-month, longitudinal study of 33 healthy, overweight or obese postmenopausal women (BMI: 25–46 kg/m²) was conducted. Abdominal and gluteal adipose tissue samples were obtained before and after AEX + WL (n = 17) and WL (n = 16). ZAG expression was determined by RT-PCR.

Results

Prior to interventions, abdominal ZAG expression was negatively correlated with visceral fat (r = − 0.50, P < 0.005), sagittal diameter (r = − 0.42, P < 0.05), and positively related to VO₂max (r = 0.37, P < 0.05). Gluteal ZAG expression was negatively correlated with weight, fat-free mass, visceral fat, resting metabolic rate, and fasting insulin (r = − 0.39 to − 0.50, all P < 0.05). Abdominal ZAG mRNA levels increased, though not significantly, 5% after AEX + WL and 11% after WL. Gluteal ZAG mRNA levels also did not change significantly with AEX + WL and WL.

Conclusions

Abdominal ZAG expression may be important in central fat accumulation and fitness but only modestly increase (nonsignificantly) with weight reduction alone or with aerobic training in obese postmenopausal women.     

消化道不同恶性肿瘤患者血清锌α-2-糖蛋白水平检测及临床意义

目的对脂肪降解中起重要作用的脂质降解因子锌α-2-糖蛋白(zinc-α-glycoprotein,ZAG)在消化道不同恶性肿瘤患者血清中的表达进行了研究,旨在探讨这些肿瘤患者的脂质代谢状态与ZAG的关系。方法实验采集了不同消化道恶性肿瘤患者、相应良性病变及正常健康人血清样本,每种疾病及正常血清样本各6例,检测了所有样本的脂代谢相关指标。采用蛋白免疫印迹的方法对血清中锌α-2-糖蛋白(zinc-α-glycoprotein,ZAG)的含量进行了半定量鉴定。结果在各疾病组中,总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)在血清中的含量在健康对照组、良性组、恶性组间差异无统计学意义。在胃病组、结肠疾病组、直肠疾病组中,锌α-2-糖蛋白(ZAG)在恶性、良性和正常组中的表达不具有统计学意义(P=0.589,P=0.618,P=0.864)。而ZAG在肝癌患者血清中的表达与正常健康人、良性组相比,差异具有统计学意义(P=0.013,P=0.008),但正常健康人与良性组患者比较,差异无统计学意义(P=0.804)。结论锌α-2-糖蛋白(ZAG)在消化道不同肿瘤患者血清中的表达差异有统计学意义,肝癌组相对于胃癌组、结直肠癌组的表达具有临床诊断意义。与总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)相比,它在评价肝癌患者脂代谢状态方面更加灵敏。     

α锌脂糖蛋白在肝癌病人血清中的表达

目的对脂肪降解中起重要作用的脂质降解因子α锌脂糖蛋白(ZAG)在肝癌病人血清中的表达进行了研究,旨在探讨这些肝癌病人的脂质代谢状态与ZAG的关系。方法采集肝癌、肝囊肿和正常人的血清样本,每组样本6例,检测所有样本血清中的脂代谢相关指标。采用蛋白免疫印迹的方法对血清中ZAG的表达进行了半定量鉴定。结果总胆固醇(CHOL)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)在血清中的含量在正常组、肝囊肿组、肝癌组间无明显差异。正常组与肝囊肿组相比较ZAG在血清中的表达差异不具有统计学意义(P=0.804);而正常组和肝囊肿组血清中ZAG的表达量与肝癌组相比差异具有统计学意义(P=0.013,P=0.008)。结论 ZAG在肝癌病人组血清中的表达相对于正常人组和肝囊肿组明显升高,与总胆固醇(CHOL)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)相比,ZAG在评价肝癌患者脂代谢状态方面更加灵敏。     

锌-α_2-糖蛋白(ZAG)在雄性大鼠生殖系统中表达差异的研究

目的 探讨(研究)锌-α2-糖蛋白(ZAG)在成年雄性SD大鼠生殖系统中的表达情况.方法 应用商品化试剂盒分别抽提RNA和蛋白质,利用实时荧光定量PCR(Realtime PCR)和免疫印迹(Westernblot)的方法研究ZAG在SD大鼠生殖系统各器官中的表达情况.结果 雄性SD大鼠生殖系统各器官中均有ZAG蛋白的存在,不同组织表达有一定的差异,尤其是在尾部附睾及附睾脂肪组织中表达较高,其它组织相对较低.结论 大鼠生殖系统中ZAG主要分布在尾部附睾及附睾脂肪组织.通过对ZAG蛋白在雄性SD大鼠生殖系统表达差异的研究,有助于进一步了解该蛋白在雄性生殖系统中的生物学功能.     

Characterization of ZAG protein expression in prostate cancer using a semi-automated microscope system

OBJECTIVE: Zinc-alpha-2-glycoprotein 1 (ZAG) is a 41-kD secreted protein that is known to stimulate lipid degradation in adipocytes. The aim of this study was to determine how ZAG protein expression is associated with prostate cancer (PCa). MATERIALS AND METHODS: An immunohistochemistry analysis was performed on a 227 PCa tissue microarray cases. ZAG protein expression was assessed using a semi-automated cellular image analysis system. RESULTS: ZAG expression was associated with tumor stage (pT2 > pT3 > metastasis cases, P < 0.001), and was inversely associated with Gleason score on pathology (P = 0.01). ZAG intensity was predictive of biochemical recurrence (P = 0.002). On multivariate analysis including pT2 patients, the predictive factors of biochemical recurrence were ZAG expression (P = 0.016), Gleason score (P = 0.011), and surgical margin status (P = 0.047). CONCLUSIONS: This study characterized ZAG protein expression in PCa using a semi-automated system. ZAG expression level found to have an independent prognostic value for pT2 patients.     

康莱特对老年癌症恶病质患者生存质量影响及恶病质因子的调控

目的 探讨康莱特对老年癌症恶病质( cancer cachexia,CC)患者的生存质量影响及时恶病质因子的调控作用. 方法 62例2009年1月至2011年4月住院的老年癌症患者,根据CC的诊断标准,各项评分＞5分者42例入组,分别用康莱特进行干预,比较干预前后患者KPS评分、三酰甘油(TG)、血红蛋白(HB)、血清白蛋白(ALB)、肿瘤坏死因子(TNF-2α)及新的恶病质因子锌-α2-糖蛋白(zinc-alpha 2-glycoprotein,ZAG)的变化. 结果 治疗后与治疗前相比,患者KPS评分升高,血HB和TNF-2α升高、ZAG降低(P＜0.05);TG明显升高(P＜0.01).ALB治疗前后比较没有统计学差异(P＞0.05). 结论 康莱特可以降低老年癌症患者的恶病质因子TNF-2α、ZAG水平,有改善患者恶病质症状,提高患者生存质量的作用.