p27与肿瘤的研究进展

肿瘤的发生、发展和恶变与细胞周期失控密切相关。细胞周期的顺利进行和完成依赖于一系列正负调节因子的相互作用 ,主要有细胞周期素 (cyclins)、细胞周期素依赖激酶(cyclin -dependentkinases,CDKs)和细胞周期素依赖激酶抑制蛋白 (cyclin -dependentkinaseinhibitors ,CDKIs)。CDKIs是近几年来分离得到的一类重要的细胞周期调控蛋白 ,参与细胞G1期进入S期的负调控 ,可防止细胞过度增殖和恶变。p2 7是新近发现的CDKIs家族成员之一。1 p2 7基因及其蛋白1994年 ,Polyak等[1] 在转化生长因子 - β(TGF - β)和经细胞接触处理的生长抑…     

尿视黄醇结合蛋白对慢性肾盂肾炎的诊断价值

视黄醇结合蛋白（RBP）是低分子蛋白。其尿浓度可反映肾近曲小管重吸收功能，具有灵敏度和特异度较高的特点。本文对68例慢性肾孟肾炎做尿RBP检测，并与尿β2-微球蛋白（β2-m）相比较，以评估尿RBP对慢性肾盂肾炎的临床应用价值。     

金属硫蛋白与线粒体功能调节

 金属硫蛋白（MTs）是一种富含半胱氨酸可结合金属离子的小分子蛋白,广泛分布于哺乳动物的各个器官。大量研究发现MTs具有调节金属离子稳态、重金属解毒、清除氧自由基、抑制炎症因子、防止机体衰老、贮存锌元素、防止细胞癌变、抗击电离辐射和抗细胞凋亡等多种生物学功能。近年来研究提示,MTs作为多功能蛋白可能直接或间接参与线粒体功能调节。特别是在氧化应激等条件下,MTs对于维持线粒体功能、促进线粒体损伤修复具有重要的意义。本文重点综述了金属硫蛋白对线粒体功能的调节作用及其可能机制。     

高尿酸血症的分子遗传学研究进展

高尿酸血症（HUA）是一种涉及多基因遗传变异的疾病。血尿酸稳态由尿酸生成和排泄共同调节维持。高尿酸血症患病率逐年升高,且与代谢综合征密切关联,因此对其发病机制研究也愈受重视。最近研究发现,嘌呤代谢过程中关键酶次黄嘌呤鸟嘌呤磷酸核糖转移酶（HPRT）及磷酸核糖焦磷酸合成酶（PRS）基因遗传缺陷和肾脏尿酸盐转运体系中的尿酸盐阴离子交换体（URAT1）、葡萄糖转运体9（GLU9）、三磷酸腺苷结合盒转运蛋白G2（ABCG2）、尿调节素（UMOD）和含PDZ结构域蛋白1（PDZK1）基因变异可导致尿酸稳态失衡而致高尿酸血症,但具体分子机制尚未完全清楚。本文主要对近几年高尿酸血症发病机制的分子遗传学研究进展进行综述。     

人血栓调节素放射免疫分析

从健康人尿中纯化了血栓调节素，免疫家兔产生抗血清，＾１２５Ｉ－血栓调节素用联结标记法制备，采用平衡法建立ＲＩＡ，数据有三次函数数据程序处理。方法的批内和批间ＣＶ分别为５．１０％和１０．９４％，平均回收率为１０５．２２％，可测范围为８．１￣５６０μｇ／Ｌ，ＥＤ５０为１２．５８μｇ／Ｌ，与凝血酶、蛋白Ｃ、蛋白Ｓ和蛋白Ｃ抑制物没有交叉反应。４０名健康男、女性血浆血栓调节素含量为５８．３±１０．４１μｇ／     

存活素与皮肤疾病的研究进展

存活素是近年来发现的凋亡抑制蛋白家族中的一员，它的主要作用是抑制细胞凋亡和调节细胞有丝分裂。研究发现它在人体各类肿瘤组织中高度表达，而在正常成人身体组织中弱表达或者不表达。本文对存活素的结构与功能及其与皮肤肿瘤和其他皮肤疾病的关系，以及针对存活素的治疗进行综述。     

非酒精性脂肪肝的发病机制研究进展

非酒精性脂肪性肝病(Non-alcoholic fatty liver disease,NAFLD)是一种常见的慢性肝脏疾病,可以发展成肝硬化,肝癌等严重疾病。本文对近年来关于NAFLD的发病机制进行了归纳和分析整理,发现NAFLD与诸多因素有关。在二次打击中,以胰岛素抵抗和氧化应激为中心环节,并在相关因素如脂联素、抵抗素、内脂素、瘦素、肿瘤坏死因子-α、成纤维细胞生长因子21、视黄醇结合蛋白4、载脂蛋白B、微粒体甘油三酯转运蛋白、固醇调节元件结合蛋白-1c、过氧化物酶增殖体受体、肉碱棕榈酰转移酶、肝型脂肪酸结合蛋白、解偶联蛋白、细胞色素P450、线粒体锰超氧化物歧化酶、线粒体膜通透性转换孔、肝铁沉积的作用下共同促进了NAFLD的进展。希望本文能为今后进一步的研究提供理论依据和思路。     

CD55和CD59表达的调节因素和调节机制的研究进展

补体系统是天然免疫的一个重要组成部分，具有免疫防御、免疫监视和免疫调节功能。补体活化参与了多种慢性炎症性疾病如动脉粥样硬化、缺血再灌注损伤、糖尿病血管并发症、风湿性关节炎、炎症性肠病及系统性红斑狼疮等^[1-6]。补体调节蛋白通过控制补体过度活化防止宿主细胞损伤，     

Rb基因产物抑制细胞程序性死亡

为了维持机体组织稳态和防止肿瘤发生,要求细胞增殖和程序性死亡两过程之间的协同调节。一些细胞蛋白(如c-myc蛋白、E2F转录因子)及某些 病毒蛋白(如腺病毒的ElA蛋白)具有对细胞程序性死亡和细胞增殖两过程的双重正性调节作用。抑瘤基因—视网膜母细胞瘤基因(RB)产物(pRb)能与这些蛋白质结合,且发现其具有抑制生长作用。为     

孕妇与原因不明不育妇女尿中尿调素含量的测定及意义

用ＣｏｎＡ－Ｓｅｐｈａｒｏｓｅ亲和层析柱和硅藻土吸附法自正常孕妇尿中提取得尿调素，免疫家兔制成抗血清，建立了检测尿中尿调素含量的ＥＬＩＳＡ法。经检查不同孕期的正常孕妇９０名，发现随孕期增长，尿中尿调素含量逐渐增加。同时发现原因不明的不育妇女尿中尿调素也含量显著升高。认为尿调素可能与维持正常妊娠关系不大。     

A case of familial juvenile hyperuricemic nephropathy with novel uromodulin gene mutation, a novel heterozygous missense mutation in Korea

Familial Juvenile hyperuricemic nephropathy (FJHN, OMIM #162000) is a rare autosomal dominant disorder characterized by hyperuricemia with renal uric acid under-excretion, gout and chronic kidney disease. In most but not all families with FJHN, genetic studies have revealed mutations in the uromodulin (UMOD) gene located on chromosome 16p11-p13. We here described a novel heterozygous missense mutation (c.1382C>A causing p.Ala461Glu) in an affected 16-year-old male with hyperuricemia, gout and chronic kidney disease. His father was also affected and the UMOD mutation was found to segregate with the disease. There has been only one case report of Korean family with FJHN, which has not been diagnosed by genetic study. This is the first report of genetically diagnosed FJHN in Korea.     

Localization of the Tamm-Horsfall glycoprotein (unomodulin) gene to chromosome 16p12.3-16p13.11

Mapping studies using a panel of 22 rodent-human somatic cell hybrids have helped to localize the Tamm-Horsfall glycoprotein (uromodulin) gene ( UMOD ): which has previously been reported to map to 16p13.11, to the region 16p12.3-qter. The combined results indicate that UMOD is located distal to D16S295 and proximal to D16S287 and in the region 16p12.3-16p13.11. Uromodulin is known to affect the formation of calcium-containing kidney stones, and this localization of UMOD will help in studies of families with autosomal forms of nephrolithiasis.     

UMOD as a susceptibility gene for end-stage renal disease

ABSTRACT: BACKGROUND: In recent genetic association studies, common variants including rs12917707 in the UMOD locus have shown strong evidence of association with eGFR, prevalent and incident chronic kidney disease and uromodulin urinary concentration in general population cohorts. The association of rs12917707 with end-stage renal disease (ESRD) in a recent case-control study was only nominally significant. METHODS: To investigate whether rs12917707 associates with ESRD, graft failure (GF) and urinary uromodulin levels in an independent cohort, we genotyped 1142 ESRD patients receiving a renal transplantation and 1184 kidney donors as controls. After transplantation, 1066 renal transplant recipients were followed up for GF. Urinary uromodulin concentration was measured at median [IQR] 4.2 [2.2-6.1] yrs after kidney transplantation. RESULTS: The rs12917707 minor allele showed association with lower risk of ESRD (OR 0.89 [0.76-1.03], p = 0.04) consistent in effect size and direction with the previous report (Boger et al, PLoS Genet 2011). Meta-analysis of these findings showed significant association of rs12917707 with ESRD (OR 0.91 [0.85-98], p = 0.008). In contrast, rs12917707 was not associated with incidence of GF. Urinary uromodulin concentration was lower in recipient-carriers of the donor rs12917707 minor allele as compared to non-carriers, again consistent with previous observations in general population cohorts. CONCLUSIONS: Our study thus corroborates earlier evidence and independently confirms the association between UMOD and ESRD.     

A <Emphasis Type="Italic">novel</Emphasis> heterozygous <Emphasis Type="Italic">missense</Emphasis>mutation in the UMOD gene responsible for Familial Juvenile Hyperuricemic Nephropathy

Background  

Familial Juvenile Hyperuricemic Nephropathy is an autosomal dominant nephropathy, characterized by decreased urate excretion and progressive interstitial nephritis. Mutations in the uromodulin coding UMOD gene have been found responsible for the disease in some families.     

Functional analysis of UMOD gene and its effect on inflammatory cytokines in serum of essential hypertension patients

Objective: The study aimed to investigate the function of uromodulin (UMOD) gene and its effect on inflammatory cytokines in serum of essential hypertension patients. Methods: The online database and software of computer were used for bioinformatics analysis on UMOD gene as well as the structure and function of its encoding proteins. Moreover, radioimmunoassay and enzyme linked immunosorbent assay was adopted to validate the content of urine UMOD protein of essential hypertension patients and their serum inflammatory cytokines. Results: As an alkaline and hydrophilic protein, UMOD has no transmembrane region, but it does have a signal peptide sequence. It is mainly located extracellularly, belonging to a secreted protein, whose secondary structure was based mainly on Random coil which account for 58.44%. According to function prediction, it is found that the UMOD protein has stress response which may be participate in the inflammatory reaction. It has been observed from the experiment which was designed on the basis of the correlation between inflammation reaction and essential hypertension that the content of urine UMOD protein of essential hypertension patients who is in stage I was (28.71±10.53) mg/24 h and when compared with the control group’s content (30.15±14.10 mg/24 h), the difference was not obviously; The content of urine UMOD protein of essential hypertension patients who’s in stage II and III was (18.24±6.12) mg/24 h and (9.43±3.16) mg/24 h, respectively, which were obviously lower than that of the control group (P<0.01). Additionally, the serum inflammatory cytokines, such as TNF-α, IL-6 and IL1-α content of essential hypertension patients were all markedly higher than that of control group (P<0.05). Conclusion: For essential hypertension patients, there’s a close relationship between the expression level of UMOD gene and inflammatory cytokines, which were manifested as the negative correlation between the level of the gene’s expression and inflammatory cytokines. That has certain reference value to realize the targeted treatment for essential hypertension through regulated blood pressure conversely in the view of expression level of inflammatory cytokines.     

Allelism of MCKD, FJHN and GCKD caused by impairment of uromodulin export dynamics

The disease complex medullary cystic disease/familial juvenile hyperuricemic nephropathy (MCKD/FJHN) is characterized by alteration of urinary concentrating ability, frequent hyperuricemia, tubulo-interstitial fibrosis, cysts at the cortico-medullary junction and renal failure. MCKD/FJHN is caused by mutations of the gene encoding uromodulin, the most abundant protein in urine. Here, we describe new missense mutations in three families with MCKD/FJHN and demonstrate allelism with a glomerulocystic kidney disease (GCKD) variant, showing association of cyst dilatation and collapse of glomeruli with some clinical features similar to MCKD/FJHN as hyperuricemia and impairment of urine concentrating ability. Furthermore, we provide the first functional characterization of uromodulin mutations. The four newly identified mutants were characterized by immunofluorescence and FACS analysis on transfected cells. These experiments showed that all uromodulin mutations cause a delay in protein export to the plasma membrane due to a longer retention time in the endoplasmic reticulum. Immunohistochemistry on GCKD and MCKD/FJHN kidney biopsies revealed dense intracellular accumulation of uromodulin in tubular epithelia of the thick ascending limb of Henle's loop. Electron microscopy demonstrated accumulation of dense fibrillar material within the endoplasmic reticulum. Consistently, patient urines show a severe reduction of excreted uromodulin. The maturation impairment is consistent with the clinical findings and suggests a pathogenetic mechanism leading to these kidney diseases.     

Chronic kidney disease after liver transplantation: Recent evidence

Chronic kidney disease is a common complication after liver transplantation with an incidence ranging between 20% and 80%. Studies of renal function after liver transplantation have yielded conflicting results: the wide range in incidence rates of chronic kidney disease (CKD) following liver transplantation is related to the methods for measuring kidney function, and various criteria for defining renal dysfunction, among others. An important cause of CKD among liver transplant recipients is calcineurin inhibitor-based immunosuppression. Additional predictors of CKD post-liver transplantation include pre-transplant kidney function, peri-operative acute kidney failure, age, and hepatitis C. A recent meta-analysis of observational studies revealed that, in the subgroup of studies provided with glomerular filtration rate at baseline, the summary estimate of relative risk and 95% confidence intervals (CI) for developing chronic renal failure among liver transplant recipients with diminished renal function at transplant was 2.12 (95% CI, 1.01-4.46, p=0.047). Acute renal insufficiency is common immediately after liver transplantation, whereas the course of CKD after liver transplantation appears progressive over time. Only preliminary information exists on kidney pathological findings in recipients of liver transplants with CKD. Introduction of the Model for End-stage Liver Disease for the allocation of liver grafts has not increased the occurrence of renal dysfunction following liver transplantation. Chronic kidney disease following liver transplantation increases cardiovascular burden dramatically. The use of mycophenolic acid- or sirolimus-based immunosuppression in calcineurin-inhibitors sparing protocols is an area of intense research.     

慢性肾脏病患者外周血干细胞因子水平的测定**

背景：干细胞因子是一种多功能细胞因子,在肾间质纤维化过程中起至关重要的作用。 目的：观察慢性肾脏病患者外周血干细胞因子水平的变化及其临床意义。 方法：采用ELISA法检测22例健康对照者和116例慢性肾脏病患者外周血干细胞因子水平,分析其与肾损害程度、贫血、脂质代谢紊乱、心血管病变、尿毒症皮肤瘙痒等的相关性。 结果与结论：慢性肾脏病患者外周血干细胞因子水平明显高于对照组(P < 0.01);随着肾功能减退,外周血干细胞因子水平逐渐升高,各组间相比差异有显著性意义(P < 0.05),且其水平与慢性肾脏病分期、血肌酐、尿素氮、C-反应蛋白、血酯、甲状旁腺激素呈正相关,与血红蛋白呈负相关,提示外周血干细胞因子的升高可能与慢性肾脏病进展、并发贫血等并发症的发生发展有重要关系。