scholarly journals Disease Ionomics: Understanding the Role of Ions in Complex Disease

2020 ◽  
Vol 21 (22) ◽  
pp. 8646
Author(s):  
Yan Zhang ◽  
Yinzhen Xu ◽  
Lin Zheng
Keyword(s):  
Complex Disease ◽  
Dynamic Network ◽  
Complex Diseases ◽  
Living Organism ◽  
Future Trends ◽  
Pathological Conditions ◽  
Systematic Understanding ◽  
Elemental Profiling ◽  
Made In

Ionomics is a novel multidisciplinary field that uses advanced techniques to investigate the composition and distribution of all minerals and trace elements in a living organism and their variations under diverse physiological and pathological conditions. It involves both high-throughput elemental profiling technologies and bioinformatic methods, providing opportunities to study the molecular mechanism underlying the metabolism, homeostasis, and cross-talk of these elements. While much effort has been made in exploring the ionomic traits relating to plant physiology and nutrition, the use of ionomics in the research of serious diseases is still in progress. In recent years, a number of ionomic studies have been carried out for a variety of complex diseases, which offer theoretical and practical insights into the etiology, early diagnosis, prognosis, and therapy of them. This review aims to give an overview of recent applications of ionomics in the study of complex diseases and discuss the latest advances and future trends in this area. Overall, disease ionomics may provide substantial information for systematic understanding of the properties of the elements and the dynamic network of elements involved in the onset and development of diseases.

scholarly journals Cap analysis of gene expression (CAGE) sequencing reveals alternative promoter usage in complex disease

2021 ◽  
Author(s):  
Sonal Dahale ◽  
Jorge Ruiz-Orera ◽  
Jan Silhavy ◽  
Norbert Hubner ◽  
Sebastiaan van Heesch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Complex Disease ◽  
Complex Diseases ◽  
Alternative Promoter ◽  
Brown Norway ◽  
Specific Gene ◽  
Insulin Receptor Gene ◽  
Promoter Usage ◽  
Cap Analysis

The role of alternative promoter usage in tissue specific gene expression has been well established, however, its role in complex diseases is poorly understood. We performed cap analysis of gene expression (CAGE) tag sequencing from the left ventricle (LV) of a rat model of hypertension, the spontaneously hypertensive rat (SHR), and a normotensive strain, the Brown Norway (BN) to understand role of alternative promoter usage in complex disease. We identified 26,560 CAGE-defined transcription start sites (TSS) in the rat LV, including 1,970 novel cardiac TSS resulting in new transcripts. We identified 27 genes with alternative promoter usage between SHR and BN which could lead to protein isoforms differing at the amino terminus between two strains. Additionally, we identified 475 promoter switching events where a shift in TSS usage was within 100bp between SHR and BN, altering length of the 5 prime UTR. Genomic variants located in the shifting promoter regions showed significant allelic imbalance in F1 crosses, confirming promoter shift. We found that the insulin receptor gene (Insr) showed a switch in promoter usage between SHR and BN in heart and liver. The Insr promoter shift was significantly associated with insulin levels and blood pressure within a panel of BXH/HXB recombinant inbred (RI) rat strains. This suggests that the hyperinsulinemia due to insulin resistance might lead to hypertension in SHR. Our study provides a preliminary evidence of alternative promoter usage in complex diseases.

scholarly journals Iron Metabolism in Obesity and Metabolic Syndrome

2020 ◽  
Vol 21 (15) ◽  
pp. 5529
Author(s):  
Álvaro González-Domínguez ◽  
Francisco M. Visiedo-García ◽  
Jesús Domínguez-Riscart ◽  
Raúl González-Domínguez ◽  
Rosa M. Mateos ◽  
...  
Keyword(s):  
Childhood Obesity ◽  
Iron Metabolism ◽  
Fenton Reaction ◽  
Iron Homeostasis ◽  
Living Organism ◽  
Nutritional Disorder ◽  
Nonalcoholic Fatty Liver ◽  
Pathological Conditions

Obesity is an excessive adipose tissue accumulation that may have detrimental effects on health. Particularly, childhood obesity has become one of the main public health problems in the 21st century, since its prevalence has widely increased in recent years. Childhood obesity is intimately related to the development of several comorbidities such as nonalcoholic fatty liver disease, dyslipidemia, type 2 diabetes mellitus, non-congenital cardiovascular disease, chronic inflammation and anemia, among others. Within this tangled interplay between these comorbidities and associated pathological conditions, obesity has been closely linked to important perturbations in iron metabolism. Iron is the second most abundant metal on Earth, but its bioavailability is hampered by its ability to form highly insoluble oxides, with iron deficiency being the most common nutritional disorder. Although every living organism requires iron, it may also cause toxic oxygen damage by generating oxygen free radicals through the Fenton reaction. Thus, iron homeostasis and metabolism must be tightly regulated in humans at every level (i.e., absorption, storage, transport, recycling). Dysregulation of any step involved in iron metabolism may lead to iron deficiencies and, eventually, to the anemic state related to obesity. In this review article, we summarize the existent evidence on the role of the most recently described components of iron metabolism and their alterations in obesity.

Immunomodulatory role of the extracellular matrix protein tenascin-C in neuroinflammation

2019 ◽  
Vol 47 (6) ◽  
pp. 1651-1660 ◽  
Author(s):  
Susanne Wiemann ◽  
Jacqueline Reinhard ◽  
Andreas Faissner
Keyword(s):  
Extracellular Matrix ◽  
Intracellular Signaling ◽  
Matrix Protein ◽  
Dynamic Network ◽  
Adaptor Proteins ◽  
Extracellular Matrix Protein ◽  
Tenascin C ◽  
Pathological Conditions ◽  
Main Components

The extracellular matrix (ECM) consists of a dynamic network of various macromolecules that are synthesized and released by surrounding cells into the intercellular space. Glycoproteins, proteoglycans and fibrillar proteins are main components of the ECM. In addition to general functions such as structure and stability, the ECM controls several cellular signaling pathways. In this context, ECM molecules have a profound influence on intracellular signaling as receptor-, adhesion- and adaptor-proteins. Due to its various functions, the ECM is essential in the healthy organism, but also under pathological conditions. ECM constituents are part of the glial scar, which is formed in several neurodegenerative diseases that are accompanied by the activation and infiltration of glia as well as immune cells. Remodeling of the ECM modulates the release of pro- and anti-inflammatory cytokines affecting the fate of immune, glial and neuronal cells. Tenascin-C is an ECM glycoprotein that is expressed during embryonic central nervous system (CNS) development. In adults it is present at lower levels but reappears under pathological conditions such as in brain tumors, following injury and in neurodegenerative disorders and is highly associated with glial reactivity as well as scar formation. As a key modulator of the immune response during neurodegeneration in the CNS, tenascin-C is highlighted in this mini-review.

scholarly journals Regulation of Nuclear Factor-kappaB Function by O-GlcNAcylation in Inflammation and Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Angela Rose Liu ◽  
Parameswaran Ramakrishnan
Keyword(s):  
Cell Proliferation ◽  
Posttranslational Modifications ◽  
Nuclear Factor Kappab ◽  
Nuclear Factor ◽  
Cancer Cell Proliferation ◽  
The Past ◽  
Pathological Conditions ◽  
Evolutionarily Conserved ◽  
Made In

Nuclear factor-kappaB (NF-κB) is a pleiotropic, evolutionarily conserved transcription factor family that plays a central role in regulating immune responses, inflammation, cell survival, and apoptosis. Great strides have been made in the past three decades to understand the role of NF-κB in physiological and pathological conditions. Carcinogenesis is associated with constitutive activation of NF-κB that promotes tumor cell proliferation, angiogenesis, and apoptosis evasion. NF-κB is ubiquitously expressed, however, its activity is under tight regulation by inhibitors of the pathway and through multiple posttranslational modifications. O-GlcNAcylation is a dynamic posttranslational modification that controls NF-κB-dependent transactivation. O-GlcNAcylation acts as a nutrient-dependent rheostat of cellular signaling. Increased uptake of glucose and glutamine by cancer cells enhances NF-κB O-GlcNAcylation. Growing evidence indicates that O-GlcNAcylation of NF-κB is a key molecular mechanism that regulates cancer cell proliferation, survival and metastasis and acts as link between inflammation and cancer. In this review, we are attempting to summarize the current understanding of the cohesive role of NF-κB O-GlcNAcylation in inflammation and cancer.

scholarly journals Complement synthesis in the injured kidney: does it have a role in immune complex glomerulonephritis?

1996 ◽  
Vol 7 (11) ◽  
pp. 2314-2319 ◽  
Author(s):  
S H Sacks ◽  
W Zhou ◽  
N S Sheerin
Keyword(s):  
Immune Complex ◽  
Complex Disease ◽  
Tissue Injury ◽  
Human Kidney ◽  
Current Evidence ◽  
Complement Components ◽  
Complement Component C3 ◽  
Injured Kidney ◽  
Made In

On pages 2428 to 2433 of this issue, Miyazaki et al. provide evidence that complement component C3 is synthesized within the glomeruli of patients with mesangial glomerulonephritis. Although it has been known for several years that cells isolated from the human kidney can synthesize a range of complement components, and that immune complex disease can increase the expression of these genes, it is only now that the link between intraglomerular synthesis of complement and human glomerulonephritis can be made. In view of the long interest in the role of complement in the pathogenesis of glomerulonephritis, this begs the question to what extent local complement synthesis may be involved in the generation of tissue injury. Given also the double-sided nature of complement-proinflammatory and protective-It remains to be seen if the roles of local and systemic complement differ in these respects. To weigh these questions, we examine the current evidence that connects local complement synthesis with renal injury, and ask what studies are needed to provide more definitive answers.

ASPECTS IN BUILDING A COMPANY WEB-SITE AND ITS ROLE FOR THE DEVELOPMENT OF BUSINESS

2018 ◽  
pp. 117-124
Author(s):  
Petar Halachev ◽  
Victoria Radeva ◽  
Albena Nikiforova ◽  
Miglena Veneva
Keyword(s):  
Life Cycle ◽  
Web Site ◽  
The Internet ◽  
A Company ◽  
The Web ◽  
Design Construction ◽  
Made In ◽  
Site Types

This report is dedicated to the role of the web site as an important tool for presenting business on the Internet. Classification of site types has been made in terms of their application in the business and the types of structures in their construction. The Models of the Life Cycle for designing business websites are analyzed and are outlined their strengths and weaknesses. The stages in the design, construction, commissioning, and maintenance of a business website are distinguished and the activities and requirements of each stage are specified.

Aboutness

2014 ◽  
Author(s):  
Stephen Yablo
Keyword(s):  
Subject Matter ◽  
Philosophy Of Language ◽  
Mental States ◽  
Library Science ◽  
Philosophical Methodology ◽  
Major Advance ◽  
Truth Conditions ◽  
Ways Of Being ◽  
Made In

Aboutness has been studied from any number of angles. Brentano made it the defining feature of the mental. Phenomenologists try to pin down the aboutness features of particular mental states. Materialists sometimes claim to have grounded aboutness in natural regularities. Attempts have even been made, in library science and information theory, to operationalize the notion. However, it has played no real role in philosophical semantics, which is surprising. This is the first book to examine through a philosophical lens the role of subject matter in meaning. A long-standing tradition sees meaning as truth conditions, to be specified by listing the scenarios in which a sentence is true. Nothing is said about the principle of selection—about what in a scenario gets it onto the list. Subject matter is the missing link here. A sentence is true because of how matters stand where its subject matter is concerned. This book maintains that this is not just a feature of subject matter, but its essence. One indicates what a sentence is about by mapping out logical space according to its changing ways of being true or false. The notion of content that results—directed content—is brought to bear on a range of philosophical topics, including ontology, verisimilitude, knowledge, loose talk, assertive content, and philosophical methodology. The book represents a major advance in semantics and the philosophy of language.

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Number Of Genes ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
Genetic And Environmental Factors ◽  
Made In

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

Variations in Mineral/heavy metals profiling and preventive role of trichomes in Peach Fruits treated with CaC2

2020 ◽  
Vol 23 ◽  
Author(s):  
Muhammad Irfan ◽  
Safdar Abbas ◽  
Beenish Jehan Azhar ◽  
Shakeel Ahmad ◽  
Hafsa Muhammad ◽  
...  
Keyword(s):  
Heavy Metals ◽  
Nutritional Value ◽  
Fine Powder ◽  
Calcium Carbide ◽  
Control Group ◽  
Tandem Accelerator ◽  
Health Promoting ◽  
Elemental Profiling

Background: Phytonutrients in peach fruits have health promoting antioxidants against various chronic diseases. However, there is no extensive data to show the nutritional values of Local peach cultivars after post-harvest treatments. Objective: Mainly this study was objective to determine the effect of calcium carbide on nutritional value and quality of fruits of Pakistani peach cultivars. Methods: The peach fruits were collected from three different peach orchids of KPK and the fruits were divided into 4 groups while 5th group was collected from local fruit shop. Each experimental group was treated with different concentration of calcium carbide whereas control group was not treated. The peel and pulp samples were oven dried and ground to fine powder separately. The elemental compositions were determined using Particle Induced X-ray emission and Pelletron Tandem Accelerator. Result: Sixteen elements were identified in peach fruits and the elements were Al, P, S, Cl, K, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, and Se. In peel, concentration of some elements increased or decreased after treatment with CaC2 while in pulp the conc. of nearly all detected elements was increased in treated samples. We found significantly high amount of heavy metals traces including As, Se, Co, Si, and P in peach fruits treated with CaC2. Interestingly, the presence of trichomes in peach skin prevents the transfer of these heavy metals deep into the pulp which was also verified by the elemental profiling of nectarines. Conclusion: Conclusively, the artificial ripening with CaC2 changed the nutritional value of peach fruits that has higher health risks if consume with the peel. According to our best knowledge, this is the first report that highlights the effects of CaC2 which deteriorate the nutritional value of peach fruits in Pakistan.

Biomarkers for Early Detection of Colitis-associated Colorectal Cancer - Current Concepts, Future Trends

2020 ◽  
Vol 22 (1) ◽  
pp. 137-145
Author(s):  
Tomasz Mackiewicz ◽  
Aleksander Sowa ◽  
Jakub Fichna
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Cancer Development ◽  
Sporadic Colorectal Cancer ◽  
Future Trends ◽  
Significant Progress ◽  
Current Standard ◽  
Risk Of Cancer ◽  
Histological Testing ◽  
Made In

: Colitis-associated colorectal cancer (CAC) remains a critical complication of ulcerative colitis (UC) with mortality of approximately 15%, which makes early CAC diagnosis crucial. The current standard of surveillance, with repetitive colonoscopies and histological testing of biopsied mucosa samples is burdensome and expensive, and therefore less invasive methods and reliable biomarkers are needed. Significant progress has been made thanks to continuous extensive research in this field, however no clinically relevant biomarker has been established so far. This review of the current literature presents the genetic and molecular differences between CAC and sporadic colorectal cancer and covers progress made in the early detection of CAC carcinogenesis. It focuses on biomarkers under development, which can be easily tested in samples of body fluids or breath and, once made clinically available, will help to differentiate between progressors (UC patients who will develop dysplasia) from non-progressors and enable early intervention to decrease the risk of cancer development.

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