Urinary proteomics for the study of genetic kidney diseases

Despite their low prevalence, genetic kidney diseases (GKD) still represent a serious health problem. They often lead to kidney failure and to the consequent need of dialysis or kidney transplant. To date, reliable diagnosis requires laborious genetic tests and/or a renal biopsy. Moreover, only scant and non-specific markers exist for prognostic purposes. Biomarkers assayed in an easily available and low-cost sample, such as urine, would be highly valuable. Urinary proteomics can provide clues related to their development through the identification of differentially expressed proteins codified by the affected genes, or other dis-regulated species, in total or fractionated urine, providing novel mechanistic insights. In this review, the authors summarize and discuss the results of the main proteomic investigations on GKD urine samples and in urinary extracellular vesicles.     

Accumulation of mitochondrial DNA deletions in myotubes cultured from muscles of patients with mitochondrial myopathies

 Myoblast cultures were established from muscle biopsies of two patients harboring heteroplasmic mitochondrial (mt) DNA deletions. The accumulation kinetics of the deleted mtDNA was followed during myoblast to myotube differentiation. The percent- age of deleted mtDNA was determined by quantitative PCR in myoblasts, myotubes, and muscle biopsies. The deleted form accounted for 65% of the mtDNA present in a muscle biopsy from a patient harboring a 5.6-kb deletion. The percentage of deleted mtDNA was 1.2% in myoblasts and increased progressively after differentiation, up to 12% at 21 days after the commitment time. In a second patient harboring a 2.8-kb deletion, the percentage of deleted mtDNA increased much more slowly: from 0.07% in myoblasts to 0.21% after 22 days of differentiation, as compared with 45% in the muscle biopsy. Thus, a three- and ten-fold increase, respectively, in the fraction of deleted mtDNA occurred during the differentiation of myoblasts to myotubes from the two patients. The faster accumulation of deleted mtDNA in the first patient’s cells was linked to an earlier myoblast to myotube differentiation, suggesting that the level of deleted mtDNA is inversely related to the rate of cell proliferation. Received: 16 April 1996/Accepted: 29 July 1996     

Plasma and erythrocyte manganese concentrations

This study was carried out to assess manganese (Mn) status after an acute episode of myocardial infarction. Plasma and erythrocyte Mn concentrations were measured from admission to hospital to day 15 postadmission in 21 patients suffering from acute myocardial infarction and in three control groups. The determination of Mn in these biological fluids was performed by electrothermal atomic absorption spectrometry. Plasma Mn was higher (p<0.01) and erythrocyte Mn was similar in the acute myocardial infarction group compared to healthy age-matched control group. Plasma and erythrocyte Mn remained unchanged during the 2 wk after acute myocardial infarction and were not correlated to enzyme activities. A decrease of erythrocyte Mn with age, expressed in nmol/L, was noted (p<0.02). These results suggest that plasma and erythrocyte Mn do not provide an indication of myocardial damage. Nonetheless, Mn status in elderly merits further attention.     

Neutrophil extracellular traps activate lung fibroblast to induce polymyositis‐related interstitial lung diseases via TLR9‐miR‐7‐Smad2 pathway

Excessive neutrophil extracellular trap (NET) formation may contribute to polymyositis (PM)‐associated interstitial lung diseases (ILD), but the underlying mechanism is not fully revealed. In this study, we found that NET accelerated the progression of ILD and promoted pulmonary fibrosis (PF) in vivo. miR‐7 expression was down‐regulated in lung tissue of PM group than control group, and NETs further decreased miR‐7 expression. TLR9 and Smad2 were up‐regulated in lung tissue of PM group than control group, and NETs further increased TLR9 and Smad2 expressions. In vitro experiments showed that PMA‐treated NETs accelerated the proliferation of LF and their differentiation into myofibroblast (MF), whereas DNase I decreased the promotion effect of NETs. Neutrophil extracellular trap components myeloperoxidase (MPO) and histone 3 also promoted the proliferation and differentiation of LF. In addition, we demonstrated that TLR9 involved in the regulation of NETs on LF proliferation and differentiation, and confirmed the interaction between miR‐7 and Smad2 in LF. Finally, miR‐7‐Smad2 pathway was confirmed to be involved in the regulation of TLR9 on LF proliferation and differentiation. Therefore, NETs promote PM‐related ILD, and TLR9‐miR‐7‐Smad2 signalling pathway is involved in the proliferation of LFs and their differentiation into MFs.     

Rituximab in immunologic glomerular diseases

Experimental data suggest that the B-cell antigen CD20 may play a significant role in the pathogenesis of many diseases including glomerular diseases. These and other findings underpin the central concept of B-cell-depleting therapies that target CD20 antigen as treatments for lupus nephritis, idiopathic membranous nephropathy, focal segmental glomerulosclerosis, cryglobulinemic glomerulonephritis, antibody mediated renal allograft rejection and recurrent glomerulonephritis in renal allograft. Use of rituximab as a B-cell depleting therapy has been associated with clinical improvement and has emerged as a possible adjunct or alternative treatment option in this field of nephrology.     

APE/Ref-1在中枢神经系统氧化应激反应中的保护作用

化学性质活泼的自由基（free radicals）在保持产生和清除平衡的稳衡性动态下能履行正常的生理功能,但超过生物体的清除能力则可导致多种疾病.无嘌呤/无嘧啶核酸内切酶/氧化还原因子1（apurinic/apyrimidinic endonuclease/redox-factor 1, APE/Ref-1）是一种体内分布广泛的多功能蛋白质,通过修复DNA的无嘌呤/无嘧啶（apurinic/apyrimidinic, AP）部位参与DNA的碱基切除修复(base excision repair, BER).APE/Ref-1还可通过还原许多转录因子的半胱氨酸残基使之易于与DNA结合而调控真核细胞的基因表达.APE/Ref-1的抗细胞凋亡作用使其在自由基所致中枢神经系统病变如脑缺血-再灌注损伤、神经退行性病变、脑动脉粥样硬化中发挥了重要作用.     

Deletion of peptide amidation enzymatic activity leads to edema and embryonic lethality in the mouse

Peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the COOH-terminal amidation of peptide hormones. We previously had found high expression of PAM in several regions of the developing rodent. To determine the function of PAM during mouse embryogenesis, we produced a null mutant of the PAM gene. Homozygous mutants die in utero between e14.5 and e15.5 with severe edema that is likely due to cardiovascular deficits. These defects include thinning of the aorta and carotid arteries and are very similar to those of the recently characterized adrenomedullin (AM) gene KO despite the presence of elevated immunoreactive AM in PAM KO embryos. No peptide amidation activity was detected in PAM mutant embryos, and there was no moderation of the AM-like phenotype that could be expected if any alternative peptide amidation mechanism exists in the mouse. Despite the proposed contribution of amidated peptides to neuronal cell proliferation, no alteration in neuroblast proliferation was observed in homozygous mutant embryos prior to lethality. Mice heterozygous for the mutant PAM allele develop normally and express wildtype levels of several amidated peptides despite having one half the wildtype levels of PAM activity and PAM protein. Nonetheless, both an increase in adiposity and a mild glucose intolerance developed in aged (>10 months) heterozygous mice compared to littermate controls. Ablation of PAM thus demonstrates an essential function for this gene during mouse development, while alterations in PAM activity in the adult may underlie more subtle physiologic effects.     

水稻主要病虫综合防治专家系统—系统外壳的研制

按照国家八五项目要求,以水稻病虫害管理知识为背景,笔者构建了水稻主要病虫综防专家系统外壳（ESRIPM）．并初步建立了珠江三角洲稻区主要害虫综合防治专家系统,系统中提出一种知识的组织方法,成功地把模型引入专家系统中．本系统具有知识编辑、咨询、专家系统;系统维护、4个一级子系统,系统中已装入三化螟,稻飞虱,稻纵卷叶螟等害虫综防管理的知识,并通过调试．本系统采用下拉式菜单,人机界面友好,操作简单．此专家系统外壳也适用建立其它各种害虫管理的专家系统．     

硫氧还蛋白与心血管疾病

硫氧还蛋白是细胞内最重要的二硫键还原酶,对维持细胞内蛋白质的还原状态并正常发挥功能着重要的作用,此外。硫氧还蛋白、硫氧还蛋白还原酶和硫氧还蛋白过氧化物酶组成了细胞内最重要的抗氧化系统之一,在对抗细胞的氧化应激上起着重要作用。心血管疾病是威胁人类健康的主要疾病,它与炎症反应和氧化应激有着密切的联系。文章将从硫氧还蛋白的抗氧化、抗炎、抗细胞凋亡,调控与炎症基因表达有关的核转录因子的转录活性,以及调节细胞内蛋白质的亚硝基化等诸多方面阐述硫氧还蛋白在防御心血管疾病方面可能具有的生物学功能。