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    DJ-1 as a Therapeutic Target Against Cancer.
    Adv Exp Med Biol 2017 ;1037:203-222
    Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
    DJ-1 is a gene involved in various cellular processes, including transcriptional regulation, oxidative stress response, fertilization, mitochondrial regulation, inflammatory and fibrogenic niche formation, and glycation damage prevention. Although a disease-associated genetic study within the past decade has demonstrated that the mutation of DJ-1 is associated with autosomal early-onset Parkinson's disease, increasing evidence suggests that DJ-1 also plays a critical role in tumor development and progression. In this review, we provide an overview of current knowledge concerning the role and the mechanism of DJ-1 in cancer and also discuss the possibility of DJ-1 as a therapeutic target against cancer. Read More

    Therapeutic Activities of DJ-1 and Its Binding Compounds Against Neurodegenerative Diseases.
    Adv Exp Med Biol 2017 ;1037:187-202
    Laboratory of Pharmacology and Neurobiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga, Japan.
    Parkinson's disease (PD) is a progressive neurodegenerative disorder that is primarily characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway. Loss-of-function mutations in the gene encoding PARK7/DJ-1 were identified in familial PD. Wild-type DJ-1 acts as an oxidative stress sensor in neural cells. Read More

    The Role of the Antioxidant Protein DJ-1 in Type 2 Diabetes Mellitus.
    Adv Exp Med Biol 2017 ;1037:173-186
    Institute of Metabolic Physiology, Department of Biology, Heinrich Heine University, D-40225, Düsseldorf, Germany.
    Type 2 diabetes mellitus (T2DM) is a worldwide escalating health disorder resulting from insulin resistance and functional loss of insulin-producing beta cells that finally cause chronically elevated blood glucose concentrations. Here we review the role of ubiquitously expressed antioxidant protein DJ-1 in the pathogenesis of T2DM. In beta cells, DJ-1 protects against oxidative stress, endoplasmic reticulum stress, and streptozotocin- and cytokine-induced stress and preserves beta cell viability and insulin secretion. Read More

    DJ-1 as a Biomarker of Parkinson's Disease.
    Adv Exp Med Biol 2017 ;1037:149-171
    Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1-3 Miyakodani, Tatara, Kyotanabe, Kyoto, 610-0394, Japan.
    Parkinson's disease is a progressive, age-related, neurodegenerative disorder, and oxidative stress is an important mediator in its pathogenesis. DJ-1 has been identified as a causative gene of a familial form of Parkinson's disease, PARK7, and plays a significant role in antioxidative defense, protecting cells from oxidative stress. A cysteine residue of DJ-1 at position 106 (Cys-106) is preferentially oxidized under oxidative stress. Read More

    Protein Repair from Glycation by Glyoxals by the DJ-1 Family Maillard Deglycases.
    Adv Exp Med Biol 2017 ;1037:133-147
    Stress Molecules, Institut Jacques Monod, Université Paris 7, UMR 7592, 15 rue Hélène Brion, 75013, Paris, France.
    DJ-1 and its prokaryotic homologs, Hsp31, YhbO and YajL from Escherichia coli and PfpI from Pyrococcus furiosus, repair proteins from glycation by glyoxals (R-CO-CHO), which constitute their major glycating agents. Glycation is a non-enzymatic covalent reaction discovered by Louis Camille Maillard in 1912, between reactive carbonyls (reducing sugars and glyoxals) and amino acids (cysteine, arginine and lysine), which inactivates proteins. By degrading Maillard adducts formed between carbonyls and thiols or amino groups, the DJ-1 family Maillard deglycases prevent the formation of the so-called advanced glycation end products (AGEs) that arise from Maillard adducts after dehydrations, oxidations and rearrangements. Read More

    Regulation of Signal Transduction by DJ-1.
    Adv Exp Med Biol 2017 ;1037:97-131
    Center for Neurodegenerative and Neuroimmunologic Diseases, Department of Neurology, Rutgers - Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA.
    The ability of DJ-1 to modulate signal transduction has significant effects on how the cell regulates normal processes such as growth, senescence, apoptosis, and autophagy to adapt to changing environmental stimuli and stresses. Perturbations of DJ-1 levels or function can disrupt the equilibrium of homeostatic signaling networks and set off cascades that play a role in the pathogenesis of conditions such as cancer and Parkinson's disease.DJ-1 plays a major role in various pathways. Read More

    Transcriptional Regulation of DJ-1.
    Adv Exp Med Biol 2017 ;1037:89-95
    Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, 060-0812, Japan.
    DJ-1 is an oncogene and also a causative gene for familial Parkinson's disease. DJ-1 has various functions, and the oxidative status of a cysteine residue at position 106 (C106) is crucial for determination of the activation level of DJ-1.DJ-1 binds to many proteins, including various transcription factors, and acts as a coactivator or corepressor for regulating their target genes without direct binding to DNA, thereby affecting various cell functions. Read More

    The Multifaceted Roles of DJ-1 as an Antioxidant.
    Adv Exp Med Biol 2017 ;1037:67-87
    School of Natural Sciences, Griffith University, Nathan, QLD, 4111, Australia.
    The DJ-1 protein was originally linked with Parkinson's disease and is now known to have antioxidant functions. The protein has three redox-sensitive cysteine residues, which are involved in its dimerisation and functional properties. A mildly oxidised form of DJ-1 is the most active form and protects cells from oxidative stress conditions. Read More

    Role of DJ-1 in Fertilization.
    Adv Exp Med Biol 2017 ;1037:61-66
    Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science, Peking University Health Science Center, Beijing, 100191, China.
    Neither a sperm nor an egg can develop into an individual alone. Only when the sperm and egg bind and fuse, which is known as fertilization, can they acquire the ability of developing into new individuals. DJ-1 was reported to be involved in the process of fertilization. Read More

    Expression of DJ-1 in Cancer Cells: Its Correlation with Clinical Significance.
    Adv Exp Med Biol 2017 ;1037:45-59
    Department of Pathology, Kyoundo Hospital, Sasaki Institute, 101-0062 2-2 Kandasurugadai, Chiyoda-ku, Tokyo, Japan.
    Upregulation of DJ-1 mRNA is commonly observed in various human cancers such as ductal carcinoma of the breast, non-small cell carcinoma of the lung, pancreatic duct adenocarcinoma, urinary transitional cell carcinoma, and gynecologic carcinoma. At the protein level, intensity and intracellular localization of DJ-1 expression is varied, and the DJ-1 protein regulates cancer progression, clinical aggressiveness, differentiation, cancer cell morphology, and drug sensitivity. Thus, DJ-1 plays a critical role in cancer. Read More

    Expression of DJ-1 in Neurodegenerative Disorders.
    Adv Exp Med Biol 2017 ;1037:25-43
    Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, 1, Wakefield Street, WC1N 1PJ, London, UK.
    In 2003, autosomal recessive loss-of-function mutations were identified in PARK7 gene that caused early-onset Parkinson's disease (PD). The PARK7 gene encodes a conserved protein termed DJ-1. DJ-1 is a ubiquitous protein, and within the brain, it is present in the nucleus and cytoplasm of both neuronal and glial cells. Read More

    Structural Biology of the DJ-1 Superfamily.
    Adv Exp Med Biol 2017 ;1037:5-24
    Department of Biochemistry and the Redox Biology Center, University of Nebraska, Lincoln, NE, 68588, USA.
    The DJ-1 (also called the DJ-1/PfpI, ThiJ/PfpI, or DJ-1/ThiJ/PfpI) superfamily is a structural and functional diverse group of proteins that are present in most organisms. Many of these proteins remain poorly characterized at the biochemical level, but include some known chaperones, proteases, and various stress response proteins that remain mechanistically mysterious. This chapter outlines what is known from a structural perspective about the cellular and biochemical functions of many of these proteins from distinct clades of the superfamily in several organisms. Read More

    Adv Exp Med Biol 2017 ;1037:1-4
    Faculty of Agriculture, Hokkaido University, Kita 9, Nishi 9, Kita-ku, Sapporo, 060-8589, Japan.
    The DJ-1 gene is an oncogene and also causative gene for a familial form of Parkinson disease. Although exits of cancer and neurodegenerative diseases, including Parkinson disease, are completely opposite, there are some common points of view between both diseases, including growth and death signaling pathways, and oxidative stresses affect the onset and pathogenesis of both cancer and neurodegenerative diseases. DJ-1 has versatile functions and plays a role in protection against oxidative stress. Read More

    Cancer Stem Cells in Head and Neck Carcinomas: Identification and Possible Therapeutic Implications.
    Adv Exp Med Biol 2017 Nov 15. Epub 2017 Nov 15.
    Institute for Cellular and Molecular Medicine (ICMM), Department of Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
    The recurrence and/or lack of response of certain tumors to radio- and chemotherapy has been attributed to a small subpopulation of cells termed cancer stem cells (CSCs). CSCs have been identified in many tumors (including solid and hematological tumors). CSCs are characterized by their capacity for self-renewal, their ability to introduce heterogeneity within a tumor mass and its metastases, genomic instability, and their insensitivity to both radiation and chemotherapy. Read More

    Contrasting Views on the Role of Mesenchymal Stromal/Stem Cells in Tumour Growth: A Systematic Review of Experimental Design.
    Adv Exp Med Biol 2017 Nov 15. Epub 2017 Nov 15.
    Institute for Cellular and Molecular Medicine, Department of Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
    The effect of mesenchymal stromal/stem cells (MSCs) on tumour growth remains controversial. Experimental evidence supports both an inhibitory and a stimulatory effect. We have assessed factors responsible for the contrasting effects of MSCs on tumour growth by doing a meta-analysis of existing literature between 2000 and May 2017. Read More

    The Role of Reactive Oxygen Species in Adipogenic Differentiation.
    Adv Exp Med Biol 2017 Nov 15. Epub 2017 Nov 15.
    Department of Immunology and Institute for Cellular and Molecular Medicine; SAMRC Extramural Unit for Stem Cell Research and Therapy; Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
    Interest in reactive oxygen species and adipocyte differentiation/adipose tissue function is steadily increasing. This is due in part to a search for alternative avenues for combating obesity, which results from the excess accumulation of adipose tissue. Obesity is a major risk factor for complex disorders such as cancer, type 2 diabetes, and cardiovascular diseases. Read More

    P2Y11 Receptors: Properties, Distribution and Functions.
    Adv Exp Med Biol 2017 Sep 27. Epub 2017 Sep 27.
    Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, UK.
    The P2Y11 receptor is a G protein-coupled receptor that is stimulated by endogenous purine nucleotides, particularly ATP. Amongst P2Y receptors it has several unique properties; (1) it is the only human P2Y receptor gene that contains an intron in the coding sequence; (2) the gene does not appear to be present in the rodent genome; (3) it couples to stimulation of both phospholipase C and adenylyl cyclase. Its absence in mice and rats, along with a limited range of selective pharmacological tools, has hampered the development of our knowledge and understanding of its properties and functions. Read More

    The Future of CRISPR Applications in the Lab, the Clinic and Society.
    Adv Exp Med Biol 2017 ;1016:157-178
    Department of Clinical Medicine, St. James' Hospital, Dublin, Ireland, James's Street, Dublin 8, Dublin, Leinster, D08 NHY1, Ireland.
    CRISPR (clustered regularly interspaced short palindromic repeats) has emerged as one of the premiere biological tools of the century. Even more so than older genome editing techniques such as TALENs and ZFNs, CRISPR provides speed and ease-of-use heretofore unheard of in agriculture, the environment and human health. The ability to map the function of virtually every component of the genome in a scalable, multiplexed manner is unprecedented. Read More

    CRISPR in the Retina: Evaluation of Future Potential.
    Adv Exp Med Biol 2017 ;1016:147-155
    Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
    Clustered regularly interspaced short palindromic repeats (CRISPR) has been gaining widespread attention for its ability for targeted genome surgery. In treating inherited retinal degenerations, gene therapies have had varied results; the ones effective in restoring eye sight are limited by transiency in its effect. Genome surgery, however, is a solution that could potentially provide the eye with permanent healthy cells. Read More

    Target Discovery for Precision Medicine Using High-Throughput Genome Engineering.
    Adv Exp Med Biol 2017 ;1016:123-145
    New York Genome Center, 101 Avenue of the Americas, New York, NY, 10013, USA.
    Over the past few years, programmable RNA-guided nucleases such as the CRISPR/Cas9 system have ushered in a new era of precision genome editing in diverse model systems and in human cells. Functional screens using large libraries of RNA guides can interrogate a large hypothesis space to pinpoint particular genes and genetic elements involved in fundamental biological processes and disease-relevant phenotypes. Here, we review recent high-throughput CRISPR screens (e. Read More

    CRISPR: From Prokaryotic Immune Systems to Plant Genome Editing Tools.
    Adv Exp Med Biol 2017 ;1016:101-120
    C4 Rice Center, Genetics and Biotechnology Department, International Rice Research Institute, DAPO 7777, Manila, 1301, Philippines.
    The clustered regularly interspaced short palindromic repeats (CRISPR) system is a prokaryotic adaptive immune system that has the ability to identify specific locations on the bacteriophage (phage) genome to create breaks in it, and internalize the phage genome fragments in its own genome as CRISPR arrays for memory-dependent resistance. Although CRISPR has been used in the dairy industry for a long time, it recently gained importance in the field of genome editing because of its ability to precisely target locations in a genome. This system has further been modified to locate and target any region of a genome of choice due to modifications in the components of the system. Read More

    Genome Editing to Study Ca(2+) Homeostasis in Zebrafish Cone Photoreceptors.
    Adv Exp Med Biol 2017 ;1016:91-100
    Departments of Biochemistry and Ophthalmology, University of Washington, UW Medicine, 750 Republican St, Box 358058, Seattle, WA, 98109, USA.
    Photoreceptors are specialized sensory neurons with unique biological features. Phototransduction is well understood due in part to the exclusive expression and function of the molecular components of this cascade. Many other processes are less well understood, but also extremely important for understanding photoreceptor function and for treating disease. Read More

    A Transgenic Core Facility's Experience in Genome Editing Revolution.
    Adv Exp Med Biol 2017 ;1016:75-90
    Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC7007, Cincinnati, OH, 45229, USA.
    The use of animal models, particularly rodents, has been immensely important to nearly all aspects of biomedical research, from basic science exploration to translational discoveries into clinical applications. The transgenic core facility that provides animal model production, preservation, and recovery services has been fundamental to the success of research efforts using animals. Recent advances in genome editing technologies, especially the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) enzyme system, have transformed the tedious animal model production into a simple and effective procedure. Read More

    From Reductionism to Holism: Toward a More Complete View of Development Through Genome Engineering.
    Adv Exp Med Biol 2017 ;1016:45-74
    Department of Biochemistry and Molecular Biophysics and Systems Biology, Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, 612 West 130th Street, 9th Floor, New York, NY, 10027, USA.
    Paradigm shifts in science are often coupled to technological advances. New techniques offer new roads of discovery; but, more than this, they shape the way scientists approach questions. Developmental biology exemplifies this idea both in its past and present. Read More

    Combining Engineered Nucleases with Adeno-associated Viral Vectors for Therapeutic Gene Editing.
    Adv Exp Med Biol 2017 ;1016:29-42
    Department of Bioengineering, University of California, Berkeley, 203 Stanley Hall, UC Berkeley, Berkeley, CA, 94720, USA.
    With the recent advent of several generations of targeted DNA nucleases, most recently CRISPR/Cas9, genome editing has become broadly accessible across the biomedical community. Importantly, the capacity of these nucleases to modify specific genomic loci associated with human disease could render new classes of genetic disease, including autosomal dominant or even idiopathic disease, accessible to gene therapy. In parallel, the emergence of adeno-associated virus (AAV) as a clinically important vector raises the possibility of integrating these two technologies towards the development of gene editing therapies. Read More

    Viral Vectors, Engineered Cells and the CRISPR Revolution.
    Adv Exp Med Biol 2017 ;1016:3-27
    Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
    Over the past few decades the ability to edit human cells has revolutionized modern biology and medicine. With advances in genome editing methodologies, gene delivery and cell-based therapeutics targeted at treatment of genetic disease have become a reality that will become more and more essential in clinical practice. Modifying specific mutations in eukaryotic cells using CRISPR-Cas systems derived from prokaryotic immune systems has allowed for precision in correcting various disease mutations. Read More

    Gene and Cell Therapy for β-Thalassemia and Sickle Cell Disease with Induced Pluripotent Stem Cells (iPSCs): The Next Frontier.
    Adv Exp Med Biol 2017 ;1013:219-240
    Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1044A, New York, NY, 10029, USA.
    In recent years, breakthroughs in human pluripotent stem cell (hPSC) research, namely cellular reprogramming and the emergence of sophisticated genetic engineering technologies, have opened new frontiers for cell and gene therapy. The prospect of using hPSCs, either autologous or histocompatible, as targets of genetic modification and their differentiated progeny as cell products for transplantation, presents a new paradigm of regenerative medicine of potential tremendous value for the treatment of blood disorders, including beta-thalassemia (BT) and sickle cell disease (SCD). Despite advances at a remarkable pace and great promise, many roadblocks remain before clinical translation can be realistically considered. Read More

    Genome Editing for the β-Hemoglobinopathies.
    Adv Exp Med Biol 2017 ;1013:203-217
    Department of Pediatrics, Stanford University, Lorry Lokey Stem Cell Research Building MC5462, 1291 Welch Rd, Stanford, CA, 94305, USA.
    The β-hemoglobinopathies are diverse set of disorders caused by mutations in the β-globin (HBB) gene. Because HBB protein is a critical component (along with α-globin, heme, and iron) of hemoglobin, the molecule essential for oxygen delivery to tissues, mutations in HBB can result in lethal diseases or diseases with multi-organ dysfunction. HBB mutations can be roughly divided into two categories: those that cause a dysfunctional protein (such as sickle cell disease but also including varied diseases caused by high-affinity hemoglobins, low-affinity hemoglobins, and methemoglobinemia) and those that cause the insufficient production of HBB protein (β-thalassemia). Read More

    Reactivation of Fetal Hemoglobin for Treating β-Thalassemia and Sickle Cell Disease.
    Adv Exp Med Biol 2017 ;1013:177-202
    G Carl Huber Professor and Chair Cell and Developmental Biology, University of Michigan, 109 Zina Pitcher Place, 3035 BSRB, Ann Arbor, MI, 48109, USA.
    Reactivation of fetal hemoglobin (HbF) in adult hematopoietic cells has the potential for great clinical benefit in patients bearing deleterious mutations in the β-globin gene, such as β-thalassemia and sickle cell disease (SCD), since increasing the production of HbF can compensate for underproduction of β-globin chains (in β-thalassemia) and it can also disrupt sickle hemoglobin polymerization (in SCD). Thus for the past few decades, concerted efforts have been made to identify an effective way to induce the synthesis of HbF in adult erythroid cells for potential therapeutic relief from the effects of these β-globinopathies. Chemical inducers of HbF as well as a number of transcription factors that are able to reactivate HbF synthesis in vitro and in vivo in adult erythroid cells have been identified. Read More

    Gene Addition Strategies for β-Thalassemia and Sickle Cell Anemia.
    Adv Exp Med Biol 2017 ;1013:155-176
    Division of Hematology-Oncology, Department of Pediatrics, Weill Cornell Medical College, 515 E. 71st St., S702, Box 284, New York, NY, 10021, USA.
    Beta-thalassemia and sickle cell anemia are two of the most common diseases related to the hemoglobin protein. In these diseases, the beta-globin gene is mutated, causing severe anemia and ineffective erythropoiesis. Patients can additionally present with a number of life-threatening co-morbidities, such as stroke or spontaneous fractures. Read More

    Alternative Donor/Unrelated Donor Transplants for the β-Thalassemia and Sickle Cell Disease.
    Adv Exp Med Biol 2017 ;1013:123-153
    Molecular and Clinical Hematology Branch, National Institutes of Health, National Heart, Lung and Blood Institute, 9000 Rockville Pike, Bldg 10 9N112, Bethesda, MD, 20892, USA.
    Considerable progress with respect to donor source has been achieved in allogeneic stem cell transplant for patients with hemoglobin disorders, with matched sibling donors in the 1980s, matched unrelated donors and cord blood sources in the 1990s, and haploidentical donors in the 2000s. Many studies have solidified hematopoietic progenitors from matched sibling marrow, cord blood, or mobilized peripheral blood as the best source-with the lowest graft rejection and graft versus host disease (GvHD), and highest disease-free survival rates. For patients without HLA-matched sibling donors, but who are otherwise eligible for transplant, fully allelic matched unrelated donor (8/8 HLA-A, B, C, DRB1) appears to be the next best option, though an ongoing study in patients with sickle cell disease will provide data that are currently lacking. Read More

    Allogeneic/Matched Related Transplantation for β-Thalassemia and Sickle Cell Anemia.
    Adv Exp Med Biol 2017 ;1013:89-122
    Pediatric Hematology Department, Referral Thalassemia Center, La Timone, Marseille, France.
    Allogeneic hematopoietic stem cell transplantation (HSCT) can cure single gene disorders such as thalassemia and sickle cell anemia (SCA). These non-malignant diseases have in common severe hemolytic anemia and high proliferative bone marrow, requiring frequent transfusions. The risk of rejection is high and graft-vs-host disease is not desirable. Read More

    Current Standards of Care and Long Term Outcomes for Thalassemia and Sickle Cell Disease.
    Adv Exp Med Biol 2017 ;1013:59-87
    Hematology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45220, USA.
    Thalassemia and sickle cell disease (SCD) are disorders of hemoglobin that affect millions of people worldwide. The carrier states for these diseases arose as common, balanced polymorphisms during human history because they afforded protection against severe forms of malaria. These complex, multisystem diseases are reviewed here with a focus on current standards of clinical management and recent research findings. Read More

    Genetic Basis and Genetic Modifiers of β-Thalassemia and Sickle Cell Disease.
    Adv Exp Med Biol 2017 ;1013:27-57
    Sickle Cell Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Building 10, Room 6S241 MSC 1589, 10 Center Dr., Bethesda, MD, 20892-1589, USA.
    β-thalassemia and sickle cell disease (SCD) are prototypical Mendelian single gene disorders, both caused by mutations affecting the adult β-globin gene. Despite the apparent genetic simplicity, both disorders display a remarkable spectrum of phenotypic severity and share two major genetic modifiers-α-globin genotype and innate ability to produce fetal hemoglobin (HbF, α2γ2).This article provides an overview of the genetic basis for SCD and β-thalassemia, and genetic modifiers identified through phenotype correlation studies. Read More

    Clinical Features of β-Thalassemia and Sickle Cell Disease.
    Adv Exp Med Biol 2017 ;1013:1-26
    Division of Hematology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 11027, Cincinnati, OH, 45229, USA.
    Sickle cell disease (SCD) and β-thalassemia are among the most common inherited diseases, affecting millions of persons globally. It is estimated that 5-7% of the world's population is a carrier of a significant hemoglobin variant. Without early diagnosis followed by initiation of preventative and therapeutic care, both SCD and β-thalassemia result in significant morbidity and early mortality. Read More

    Dose Quantification in UV Phototherapy.
    Adv Exp Med Biol 2017 ;996:349-360
    Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Gray Laboratory, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford, OX3 7DQ, UK.
    Ultraviolet light has long been used to alleviate a number of skin conditions, and its efficacy is well known. However, over-exposure to ultraviolet radiation has a number of detrimental effects and thus it is vital to maintain a dose to skin within the therapeutic window. To maximise treatment gain whilst circumventing potential side-effects of over-exposure requires accurate determination of irradiance and skin-dose. Read More

    UV Driven Tanning Salons: Danger on Main Street.
    Adv Exp Med Biol 2017 ;996:335-346
    Centre de Recherche en Cancérologie de Lyon, Univ Lyon, Université Claude Bernard Lyon 1, INSERM1052, CNRS 5286, Centre Léon Bérard, 28 rue Laënnec, Cedex 08, 69373, Lyon, France.
    Appearing in the early 1980s, at a time when UVA was considered as relatively safe, the tanning industry has substantially developed in occidental countries, especially in Northern European countries. In Europe, the erythemally-weighted irradiance of a modern sunbed should not exceed 0.3 W/m(2), equivalent to an UV index of 12, i. Read More

    Safety and Efficacy of Phototherapy in the Management of Eczema.
    Adv Exp Med Biol 2017 ;996:319-331
    Department of Specialized, Diagnostic and Experimental Medicine, Division of Dermatology, University of Bologna, via Massarenti 1, 40138, Bologna, Italy.
    Atopic Dermatitis (AD), a common skin disease, can occur in patients of all age, gender and ethnicity. It is an inflammatory affection, characterized by chronic and highly debilitating behavior. First-line interventions against AD include environmental measures and topical emollients, corticosteroids or calcineurin inhibitors. Read More

    From UV Protection to Protection in the Whole Spectral Range of the Solar Radiation: New Aspects of Sunscreen Development.
    Adv Exp Med Biol 2017 ;996:311-318
    Center of Experimental and Applied Cutaneous Physiology, Department of Dermatology, Venerology and Allergology, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany.
    Sunscreens have been constantly improving in the past few years. Today, they provide an efficient protection not only in the UVB but also in the UVA spectral region of the solar radiation. Recently it could be demonstrated that 50% of all free radicals induced in the skin due to solar radiation are formed in the visible and infrared spectral region. Read More

    Ultraviolet Irradiation of Blood: "The Cure That Time Forgot"?
    Adv Exp Med Biol 2017 ;996:295-309
    Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
    Ultraviolet blood irradiation (UBI) was extensively used in the 1940s and 1950s to treat many diseases including septicemia, pneumonia, tuberculosis, arthritis, asthma and even poliomyelitis. The early studies were carried out by several physicians in USA and published in the American Journal of Surgery. However with the development of antibiotics, UBI use declined and it has now been called "the cure that time forgot". Read More

    Phototherapy of Psoriasis, a Chronic Inflammatory Skin Disease.
    Adv Exp Med Biol 2017 ;996:287-294
    Department of Dermatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
    Phototherapy is an effective treatment modality for several skin diseases which has been in use from the era of the Egyptians. Insight into its mode of action has gradually accumulated over the past decades. A crucial biological effect of ultraviolet radiation is the induction of apoptosis in T lymphocytes and in keratinocytes in the epidermis. Read More

    Phototherapy in Atopic Dermatitis.
    Adv Exp Med Biol 2017 ;996:279-286
    Dermatology Department, University General Hospital of Valencia, Av. Tres Cruces n°2, 46014, Valencia, Spain.
    Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. Currently management of AD includes avoidance of triggering factors, skin care aiming to compensate the skin barrier defects, anti-inflammatory therapy (mostly topical corticosteroids and topical calcineurin inhibitors). When these first-line approaches are unsuccessful, systemic treatment or phototherapy ought to be carried out as next line of defence. Read More

    UV Disinfection of Wastewater and Combined Sewer Overflows.
    Adv Exp Med Biol 2017 ;996:267-275
    Division of Environmental Engineering and Energy Systems, Department of Civil Engineering, University of Toronto, 35 St. George Street, Toronto, ON, M5S 1A4, Canada.
    Municipal wastewater contains bacteria, viruses, and other pathogens that adversely affect the environment, human health, and economic activity. One way to mitigate these effects is a final disinfection step using ultraviolet light (UVL). The advantages of UVL disinfection, when compared to the more traditional chlorine, include no chlorinated by-products, no chemical residual, and relatively compact size. Read More

    Role of Ultraviolet Disinfection in the Prevention of Surgical Site Infections.
    Adv Exp Med Biol 2017 ;996:255-266
    Xenex Disinfection Services, LLC, San Antonio, TX, USA.
    The role of the environment in surgical site infections is surprisingly understudied. UV disinfection holds promise for reducing the level of contamination in operating rooms and thereby lowering the risk of infection for patients. Issues such as the frequency, amount and locations for UV disinfection to have an impact on the risk of surgical site infection are recently emerging in the literature. Read More

    UV Induced Mutagenicity in Water: Causes, Detection, Identification and Prevention.
    Adv Exp Med Biol 2017 ;996:241-253
    KWR Watercycle Research Institute, P O Box 1072, 3430 BB, Nieuwegein, The Netherlands.
    At first it seemed that UV processes for disinfection and advanced oxidation were "harmless", as they didn't involve the addition of "dangerous" chemicals nor seemed to result in the formation of toxic byproducts. However, recently it has become clear that also during UV processes mutagentic/genotoxic byproducts may be formed. It was found that these are nitrogen containing aromatic compounds, which are formed by the reaction of photolysis products of nitrate with (photolysis products of) natural organic matter. Read More

    Biofilms: Microbial Strategies for Surviving UV Exposure.
    Adv Exp Med Biol 2017 ;996:233-239
    Department of Bioengineering, iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001, Lisboa, Portugal.
    Biofilm communities are an ingenious form of protection of microbial cells which have been evolving for billion of years. In general, ultraviolet (UV) radiation presents poor penetration in the matrix of biofilms and only the first few top layers of microbial cells are exposed to its deleterious effects. For further protection against UV radiation, exposed cells can produce specialized compounds such as mycosporine-like amino acids and carotenoid pigments. Read More

    Vitamin D, Cardiovascular Disease and Risk Factors.
    Adv Exp Med Biol 2017 ;996:221-230
    Research Centre for Prevention and Health, Capital Region of Denmark, Glostrup Hospital, Nordre Ringvej 57, DK-2600, Glostrup, Denmark.
    Observational studies have suggested a possible protective role of vitamin D on the cardiovascular system. The available evidence does not support either cardiovascular benefits or harms of vitamin D supplementation. This chapter provides an overview and discussion of the current knowledge of vitamin D effects from a cardiovascular health perspective. Read More

    Impact of UV Radiation on Genome Stability and Human Health.
    Adv Exp Med Biol 2017 ;996:207-219
    Department of Botany, UGC Centre of Advanced Studies, The University of Burdwan, Golapbag Campus, Burdwan, West Bengal, 713104, India.
    Gradual depletion of the atmospheric ozone layer during the past few years has increased the incidence of solar UV radiation specifically the UV-C on earth's surface is one of the major environmental concerns because of the harmful effects of this radiation in all forms of life. The solar UV radiation including the harmful wavelength range of UV-B (280-320 nm) represents a significant climatic stress for both animals and plants, causing damage to the fundamental biomolecules such as DNA, proteins and lipids, thus activating genotoxic stress and induces genome instability. When DNA absorbs UV-B light, energy from the photon causes covalent linkages to form between adjacent pyrimidine bases, creating photoproducts, primarily cyclobutane pyrimidine dimers (CPDs) and pyrimidine-6,4-pyrimidinone photoproduct (6,4PPs). Read More

    Vitamin D and Type 2 Diabetes Mellitus.
    Adv Exp Med Biol 2017 ;996:193-205
    Endocrinology Consultant, Ain Wazein Medical Village, Lebanon- Mount of Lebanon-Shouf Area, Lebanon, PA, Lebanon.
    Type 2 diabetes mellitus (T2DM) has become a significant global health care problem and its reported incidence is increasing at an alarming rate. Despite the improvement in therapy and development of new drugs, treatment still remains insufficient especially due to the associated side effects of most available drugs. Efforts are continuing toward disease prevention and search for safer drugs. Read More

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