Identification of Biomarkers of Human Skin Ageing in Both Genders. Wnt Signalling - A Label of Skin Ageing?

The goal of our work has been to investigate the mechanisms of gender-independent human skin ageing and examine the hypothesis of skin being an adequate model of global ageing. For this purpose, whole genome gene profiling was employed in sun-protected skin obtained from European Caucasian young and elderly females (mean age 26.7±4 years [n1 = 7] and 70.75±3.3 years [n2 = 4], respectively) and males (mean age 25.8±5.2 years [n3 = 6] and 76±3.8 years [n4 = 7], respectively) using the Illumina array platform. Confirmation of gene regulation was performed by real-time RT-PCR and immunohistochemistry. 523 genes were significantly regulated in female skin and 401 genes in male skin for the chosen criteria. Of these, 183 genes exhibited increased and 340 decreased expression in females whereas 210 genes showed increased and 191 decreased expression in males with age. In total, 39 genes were common in the target lists of significant regulated genes in males and females. 35 of these genes showed increased (16) or decreased (19) expression independent of gender. Only 4 overlapping genes (OR52N2, F6FR1OP2, TUBAL3 and STK40) showed differential regulation with age. Interestingly, Wnt signalling pathway showed to be significantly downregulated in aged skin with decreased gene and protein expression for males and females, accordingly. In addition, several genes involved in central nervous system (CNS) ageing (f.i. APP, TAU) showed to be expressed in human skin and were significanlty regulated with age. In conclusion, our study provides biomarkers of endogenous human skin ageing in both genders and highlight the role of Wnt signalling in this process. Furthermore, our data give evidence that skin could be used as a good alternative to understand ageing of different tissues such as CNS.     

Cowden's Disease: Familial Goiter and Skin Hamartomas—A Report of Three Cases

Multiple hamartoma syndrome (Cowden''s disease) consists of characteristic skin lesions of the face, mucous membranes and distal extremities in association with a variety of benign and malignant internal tumors, especially of the thyroid and breast. We describe a family in which the father, daughter and son were found to have goiter associated with the skin lesions of Cowden''s disease. Review of the 40 reported cases of this syndrome indicates that thyroid disease occurs in two thirds of patients with Cowden''s disease and most often presents as goiter at an early age. Thyroid cancer has occurred in only three (7.5%) of the patients.Surgical removal of the large goiter of the son showed that it was composed of multiple encapsulated follicular adenomas and a few areas of lymphocytic thyroiditis. Studies of the thyroid tissue showed that peroxidase activity was decreased, the thyroglobulin had a reduced content of thyroxine and triiodothyronine (perhaps due to the therapeutic suppression of thyroid-stimulating hormone) and thyroxine 5''-monodeiodinase was greatly increased; increased outer ring monodeiodinase activity may be a characteristic of human follicular adenomas.     

Special Issue on “Biomarkers for Autoimmune Diseases”

<正>The journal Genomics ProteomicsBioinformatics(GPB)is now inviting submissions for a special issue(to be published in the summer of 2015)on the topic of‘‘Biomarkers for Autoimmune Diseases’’.Autoimmune diseases(AIDs)are the third most common category of disease after cancer and heart disease and affect more than 5%of the general population.AIDs result     

Amyloidosis—a Complication of Pustular Psoriasis

Two patients with generalized pustular psoriasis developed amyloidosis with a fatal outcome. It is suggested that generalized pustular psoriasis may predispose to the development of secondary amyloidosis either by prolonged stimulation of the reticuloendothelial system or through abnormal immunoglobulin synthesis.     

Engineered Sialylation of Pathogenic Antibodies In Vivo Attenuates Autoimmune Disease

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Urinary Biomarkers of Brain Diseases

Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood,there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.     

Application of the “-Omic-” technologies in phytomedicine

The proof of efficacy of phytopreparations and the determination of their mode of action are permanent challenges for an evidence-based phytotherapy. The technology platform of genomics, proteomics and metabolomics ("-omic-" technologies) are high-throughput technologies. They increase substantially the number of proteins/genes that can be detected simultaneously and have the potential to relate complex mixtures to complex effects in the form of gene/protein expression profiles. Provided that phytopreparation-specific signatures in the form of gene/protein expression profiles can be developed, these technologies will be useful for the chemical and pharmacological standardization and the proof of the toxicological potential of a plant extract. Over a long-term perspective they may economize the proof of efficacy, the determination of the mode of action of phytomedicines and allow to investigate herbal extracts without prominent active principle(s). The application of this genomics revealed already that gene expression profiles induced by single drugs and the ones induced by the combination of the same drugs can be entirely different. These results make the information of the mode of action of isolated "active principles/lead substances" of phytopreparations questionable. The application of the "-omic-" technologies may lead to a change of paradigms towards the application of complex mixtures in medicine and open the new field of phytogenomics, -proteomics and -metabolomics.     

体外皮肤刺激模型的生物标志研究进展

皮肤刺激试验是人类健康相关产品危险性评价的常见项目,传统皮肤刺激试验采用实验动物进行,成本高周期长,给动物造成一定程度的痛苦。近年来,多种替代动物试验的体外模型被开发和应用。体外试验主要通过定量检测细胞活性和代谢变化的生物标志物预测体内的效应,应用最广泛的生物标志物是细胞活性、炎性因子、胞质酶等,在生物技术的推动下,新的特异性标志物被开发和验证。     

非洲猪瘟病毒研究进展:组学视角

非洲猪瘟(African swine fever,ASF)是由非洲猪瘟病毒(African swine fever virus,ASFV)引起的一种致死率可高达100%的猪烈性传染病。ASF的传播方式复杂多样,目前无商品化疫苗可用,仅能依靠检疫结合扑杀进行防控,严重威胁全球养猪及相关行业的健康发展。阻碍ASF疫苗研发的主要因素是ASFV的基因型众多、结构复杂,以及对ASFV致病和免疫逃逸机制的认识不足。本文从基因组学、转录组学、蛋白质组学和代谢组学等层面多角度综述ASFV的生物学特性及其致病和免疫逃逸机制,以期揭开ASF这个\"杀手\"的神秘面纱,为ASFV的致病机制研究和ASF的防控提供参考。     

原虫的蛋白质组学研究进展

随着“人类基因组计划”的完成,包括双向电泳和质谱技术的蛋白质组学作为基因组学研究的补充和终点,不断增加我们对基因功能的理解,逐渐成为医学研究的中心。原虫作为医学研究的对象和工具,研究内容十分广泛。本文将从原虫生活史、致病机理、潜在疫苗以及抗药性等方面对原虫的蛋白质组学进行综述。     

Integration of omics sciences to advance biology and medicine

In the past two decades, our ability to study cellular and molecular systems has been transformed through the development of omics sciences. While unlimited potential lies within massive omics datasets, the success of omics sciences to further our understanding of human disease and/or translating these findings to clinical utility remains elusive due to a number of factors. A significant limiting factor is the integration of different omics datasets (i.e., integromics) for extraction of biological and clinical insights. To this end, the National Cancer Institute (NCI) and the National Heart, Lung and Blood Institute (NHLBI) organized a joint workshop in June 2012 with the focus on integration issues related to multi-omics technologies that needed to be resolved in order to realize the full utility of integrating omics datasets by providing a glimpse into the disease as an integrated “system”. The overarching goals were to (1) identify challenges and roadblocks in omics integration, and (2) facilitate the full maturation of ‘integromics’ in biology and medicine. Participants reached a consensus on the most significant barriers for integrating omics sciences and provided recommendations on viable approaches to overcome each of these barriers within the areas of technology, bioinformatics and clinical medicine.     

Urinary Peptidomic Analysis Identifies Potential Biomarkers for Acute Rejection of Renal Transplantation

Introduction  Human urine is a complex matrix of proteins, endogenous peptides, lipids, and metabolites. The level of any or all of these components can reflect the pathophysiological status of an individual especially of the kidney at the time of urine collection. The naturally occurring endogenous urinary peptides which are thought to be the product of several proteolytic and degradation processes may provide clinically useful biomarkers for different renal and systemic diseases. Materials and Methods  To examine if specific differences in the urinary peptidome (<10 kDa) occur at the time of acute renal transplant rejection (AR), we undertook a study of urine samples collected from biopsy-proven AR (n = 10), stable graft function (n = 10), and healthy normal control (n = 10). The peptides (<10 kDa) were extracted and fractionated with high-performance liquid chromatography followed by matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometric (MS) analysis. Results  We identified 54 endogenous peptides, including multiple peptides for Tamm–Horsfall protein (UMOD). A panel of peptides are identified which discriminate renal transplant patients with AR from stable graft. We have shown that liquid chromatography followed by MALDI is a useful tool to identify potential biomarkers, which after verification with larger patient cohort can be used as a non-invasive monitoring tool for renal transplant rejection.     

Yeast genomic databases and the challenge of the post-genomic era

Since the completion of the yeast genome sequence in 1996, three genomic databases, the Saccharomyces Genome Database, the Yeast Proteome Database, and MIPS (produced by the Munich Information Center for Protein Sequences), have organized published knowledge of yeast genes and proteins onto the framework of the genome. Now, post-genomic technologies are producing large-scale datasets of many types, and these pose new challenges for knowledge integration. This review first examines the structure and content of the three genomic databases, and then draws from them and other resources to examine the ways knowledge from the literature, genome, and post-genomic experiments is stored, integrated, and disseminated. To better understand the impact of post-genomic technologies, 20 collections of post-genomic data were analyzed relative to a set of 243 previously uncharacterized genes. The results indicate that post-genomic technologies are providing rich new information for nearly all yeast genes, but data from these experiments is scattered across many Web sites and the results from these experiments are poorly integrated with other forms of yeast knowledge. Goals for the next generation of databases are set forth which could lead to better access to yeast knowledge for yeast researchers and the entire scientific community. Electronic Publication     

Methodological advances in the discovery of protein and peptide disease markers

The quest for biomarkers has seen a renaissance due to the application of newly developed separation methodologies and advances in biomolecular mass spectrometry. It can be argued that each disease influences the physiology of an organism and that these changes should be measurable. Many diagnostic and therapeutic decisions are supported by measurable biochemical or cellular changes in plasma, serum or urine but it is unquestionable that there is a great lack in better markers for early disease detection and prevention. In this review we cover recent developments in the areas of separation science, sample preparation and mass spectrometry as applied to biomarker discovery. We focus, in particular, on the use of LC-MS and SELDI-TOF-MS as two approaches that have seen an upswing in recent years. While validation of newly discovered biomarkers or biomarker patterns and their introduction into diagnostic practice will be a long process, it is our believe that many future diagnostic tests will be based on markers discovered through novel profiling technologies as those outlined in this article.