Saving hearts through basic research

Despite the recent advances in molecular medicine and health care, cardiovascular diseases are still the leading cause of morbidity and mortality throughout the world. In 2006, nearly every other death in Germany resulted from disease of the circulatory system, and congenital heart diseases are thought to account for a high number of stillbirths and spontaneous abortions. Remarkable progress in basic research over the past decades has improved our understanding of the molecular mechanisms that govern a cardiac fate and has helped to establish cell‐based therapeutic approaches to improve the course of cardiovascular diseases. Birth Defects Research (Part C) 87:273–283, 2009. © 2009 Wiley‐Liss, Inc.     

Amyloid toxicity and platelet‐activating factor signaling

Amyloidosis is the accumulation of insoluble proteinaceous aggregates in vivo and is implicated in many neurodegenerative diseases, including Alzheimer's, Huntington's, and Parkinson's diseases. This article briefly reviews the current knowledge of amyloid aggregate toxicity and inflammatory signaling in the nervous system. In particular, we focus our attention on the role of platelet‐activating factor (PAF) as mediator of amyloid cytotoxicity. J. Cell. Physiol. 228: 1143–1148, 2013. © 2012 Wiley Periodicals, Inc.     

Immunologic aspects of human colostrum and milk—A misinterpretation

Interpretations of the demographic impact of Western diseases are frequently clouded by a failure to appreciate the complex nature of immune responses. It is commonly assumed that epidemic diseases are generally characterized by both transplacental and lacteal transmission of maternal antibodies. This is not, however, the case for viral diseases, such as measles, smallpox, and influenza–-all of which reached epidemic proportions during the post-Columbian era. In this paper I review the nature of the immune response for viral diseases, with emphasis upon measles, a disease that contributed heavily to the demise of native peoples. © 1994 Wiley-Liss, Inc.     

Gene regulatory networks in embryonic stem cells and brain development

Embryonic stem cells (ESCs) are endowed with the ability to generate multiple cell lineages and carry great therapeutic potentials in regenerative medicine. Future application of ESCs in human health and diseases will embark on the delineation of molecular mechanisms that define the biology of ESCs. Here, we discuss how the finite ESC components mediate the intriguing task of brain development and exhibit biomedical potentials to cure diverse neurological disorders. Birth Defects Research (Part C) 87:182–191, 2009. © 2009 Wiley‐Liss, Inc.     

Cover Picture: Biotechnology Journal 1/2013

Cover illustration Special issue: Methods and Advances Progress in biotechnology research relies heavily on innovative ideas and approaches. Every year, Biotechnology Journal publishes a “Methods and Advances” Special Issue, which covers the latest cutting-edge research and breakthrough technologies. For this issue's cover, we chose a design featuring 12 light bulbs, representing the 12 months of the year, each with state-of-the-art research. Image credits: ©Kletr, ©Natis, ©Sarunyu_foto, ©Scanrail, ©Sergey Niven, ©Thaut Images, ©Yahia LOUKKAL, all from Fotolia.com.     

Can flies help humans treat neurodegenerative diseases?

Neurodegenerative diseases are becoming increasingly common as life expectancy increases. Recent years have seen tremendous progress in the identification of genes that cause these diseases. While mutations have been found and cellular processes defined that are altered in the disease state, the identification of treatments and cures has proven more elusive. The process of finding drugs and therapies to treat human diseases can be slow, expensive and frustrating. Can model organisms such as Drosophila speed the process of finding cures and treatments for human neurodegenerative diseases? We pose three questions, (1) can one mimic the essential features of human diseases in an organism like Drosophila, (2) can one cure a model organisms of human disease and (3) will these efforts accelerate the identification of useful therapies for testing in mice and ultimately humans? Here we focus on the use of Drosophila to identify potential treatments for neurodegenerative diseases such as Huntington's and we discuss how well these therapies translate into mammalian systems. BioEssays 26:485–496, 2004. © 2004 Wiley Periodicals, Inc.     

Noncoding RNAs and chronic inflammation: Micro‐managing the fire within

Inflammatory responses are essential for the clearance of pathogens and the repair of injured tissues; however, if these responses are not properly controlled chronic inflammation can occur. Chronic inflammation is now recognized as a contributing factor to many age‐associated diseases including metabolic disorders, arthritis, neurodegeneration, and cardiovascular disease. Due to the connection between chronic inflammation and these diseases, it is essential to understand underlying mechanisms behind this process. In this review, factors that contribute to chronic inflammation are discussed. Further, we emphasize the emerging roles of microRNAs (miRNAs) and other noncoding RNAs (ncRNA) in regulating chronic inflammatory states, making them important future diagnostic markers and therapeutic targets. Copyright Line: © 2015 The Authors BioEssays Published by Wiley‐VCH Verlag GmbH & Co. KGaA.     

Biochemical Engineering Sciences

Cover illustration Special Issue: Biochemical Engineering Sciences. This Special Issue is a collection of the latest research in biochemical engineering science presented at the 9^th ESBES Conference in Istanbul, Turkey, in 2012. The cover illustrates the development in biochemical engineering science by showing symbols for several biochemical engineering subdisciplines, such as process engineering, strain and drug design, and material science, linked by covalent bonds in a hypothetical biological molecule. Images: © JarnoM, © Amelie Olivier, © teracreonte, © ermess, © by-studio, © Sergey Nivens, all from Fotolia.com.     

Brain-specific Diseases

Cover illustration: Brain-specific diseases. Within a decade the prevalence of neurodegenerative conditions such as stroke and Alzheimer's disease among the elderly in industrialized nations is predicted to increase dramatically. This special issue of Biotechnology Journal has been edited by Nektarios Tavernarakis from the Institute of Molecular Biology and Biotechnology, Crete, Greece, and features papers and reviews about e.g. a nanobiotech biosensor for catecholamine, huntingtin antibodies, amyotrophic lateral sclerosis and much more. Image © PhotoDisc/Getty Images     

Systemic effects of Wnt signaling

Wnt signaling plays a key role in several physiological and pathological aspects. Even if Wnt signal was first described more than 20 years ago, its role in systemic effects, such as angiogenesis and vascular disorders, bone biology, autoimmune diseases, neurological diseases, and neoplastic disorders, was only recently emerged through the use of animal and in vitro models. Moreover, Wnt signaling inhibitors, such as DKK‐1, may be advantageously considered targets for the treatment of several diseases, including osteoporosis, vascular diseases, inflammatory diseases, neurological diseases, and cancer. Nevertheless, further studies are required to provide a complete understanding of this complex signaling pathway, and especially of its role in human diseases, considering the possible advantageous effects of Wnt signaling inhibitors on the progression of disease conditions. J. Cell. Physiol. 228: 1428–1432, 2013. © 2013 Wiley Periodicals, Inc.     

Biological Stereoselectivity of Atropisomeric Natural Products and Drugs

Selected examples of natural product and drug atropisomers that exhibit stereoselectivity towards receptor and enzyme targets are reviewed. The atropisomeric preference of the receptors and enzyme binding domains makes these agents attractive molecules for drug development in the treatment of various diseases. Included are commonly recognized atropisomers containing a chiral biaryl axis along with some less common examples of atropisomers without a biaryl axis. The biological targets include: antiapoptotic proteins; bacteria; microtubules; kinases; vasopressin receptors; a G‐protein coupled receptor related to obesity; monocarboxylate transporters; tachykinin NK₁‐receptors; cyclooxygenase‐1 and squalene synthase. Chirality 25:265–274, 2013. © 2013 Wiley Periodicals, Inc.     

Structural and functional analyses of human tryptophan 2,3‐dioxygenase

Tryptophan 2,3‐dioxygenase (TDO), one of the two key enzymes in the kynurenine pathway, catalyzes the indole ring cleavage at the C2‐C3 bond of l ‐tryptophan. This is a rate‐limiting step in the regulation of tryptophan concentration in vivo, and is thus important in drug discovery for cancer and immune diseases. Here, we report the crystal structure of human TDO (hTDO) without the heme cofactor to 2.90 Å resolution. The overall fold and the tertiary assembly of hTDO into a tetramer, as well as the active site architecture, are well conserved and similar to the structures of known orthologues. Kinetic and mutational studies confirmed that eight residues play critical roles in l ‐tryptophan oxidation. Proteins 2014; 82:3210–3216. © 2014 Wiley Periodicals, Inc.     

mTOR signaling for biological control and cancer

Mammalian target of rapamycin (mTOR) is a major intersection that connects signals from the extracellular milieu to corresponding changes in intracellular processes. When abnormally regulated, the mTOR signaling pathway is implicated in a wide spectrum of cancers, neurological diseases, and proliferative disorders. Therefore, pharmacological agents that restore the regulatory balance of the mTOR pathway could be beneficial for a great number of diseases. This review summarizes current understanding of mTOR signaling and some unanswered questions in the field. We describe the composition of the mTOR complexes, upstream signals that activate mTOR, and physiological processes that mTOR regulates. We also discuss the role of mTOR and its downstream effectors in cancer, obesity and diabetes, and autism. J. Cell. Physiol. 228: 1658–1664, 2013. © 2013 Wiley Periodicals, Inc.     

Stem Cell Therapy: A New Therapeutic Option for Cardiovascular Diseases

Cardiovascular diseases are known as one of major causes of morbidity and mortality worldwide. Despite the many advancement in therapies are associated with cardiovascular diseases, it seems that finding of new therapeutic option is necessary. Cell therapy is one of attractive therapeutic platforms for treatment of a variety of diseases such as cardiovascular diseases. Among of various types of cell therapy, stem cell therapy has been emerged as an effective therapeutic approach in this area. Stem cells divided into multipotent stem cells and pluripotent stem cells. A large number studies indicated that utilization of each of them are associated with a variety of advantages and disadvantages. Multiple lines evidence indicated that stem cell therapy could be used as suitable therapeutic approach for treatment of cardiovascular diseases. Many clinical trials have been performed for assessing efficiency of stem cell therapies in human. However, stem cell therapy are associated with some challenges, but, it seems resolving of them could contribute to using of them as effective therapeutic approach for patients who suffering from cardiovascular diseases. In the current review, we summarized current therapeutic strategies based on stem cells for cardiovascular diseases. J. Cell. Biochem. 119: 95–104, 2018. © 2017 Wiley Periodicals, Inc.     

Folate action in nervous system development and disease

The vitamin folic acid has been recognized as a crucial environmental factor for nervous system development. From the early fetal stages of the formation of the presumptive spinal cord and brain to the maturation and maintenance of the nervous system during infancy and childhood, folate levels and its supplementation have been considered influential in the clinical outcome of infants and children affected by neurological diseases. Despite the vast epidemiological information recorded on folate function and neural tube defects, neural development and neurodegenerative diseases, the mechanisms of folate action in the developing neural tissue have remained elusive. Here we compiled studies that argue for a unique role for folate in nervous system development and function and its consequences to neural disease and repair. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 391–402, 2018     

Cartilage acidic protein 1, a new member of the beta‐propeller protein family with amyloid propensity

Cartilage acidic protein1 (CRTAC1) is an extracellular matrix protein of chondrogenic tissue in humans and its presence in bacteria indicate it is of ancient origin. Structural modeling of piscine CRTAC1 reveals it belongs to the large family of beta‐propeller proteins that in mammals have been associated with diseases, including amyloid diseases such as Alzheimer's. In order to characterize the structure/function evolution of this new member of the beta‐propeller family we exploited the unique characteristics of piscine duplicate genes Crtac1a and Crtac1b and compared their structural and biochemical modifications with human recombinant CRTAC1. We demonstrate that CRTAC1 has a beta‐propeller structure that has been conserved during evolution and easily forms high molecular weight thermo‐stable aggregates. We reveal for the first time the propensity of CRTAC1 to form amyloid‐like structures, and hypothesize that the aggregating property of CRTAC1 may be related to its disease‐association. We further contribute to the general understating of CRTAC1's and beta‐propeller family evolution and function. Proteins 2017; 85:242–255. © 2016 Wiley Periodicals, Inc.     

Reciprocal modulation between TH17 and other helper T cell lineages

T helper 17 (TH17) cells have well‐described roles in autoimmune disease. However, TH17 is not stable in some physiological or pathological courses. Also, TH17 cells can reciprocally modulate and convert into other helper T cell subpopulations. The fully exploring the reciprocal regulatory effects and its immunoregulatory mechanisms are becoming interesting topics in the immunological study. In this review, we summarized reciprocal modulation pattern between TH17 cell and other helper T cell subpopulations in the mouse model of autoimmune diseases and human diseases. J. Cell. Physiol. 226: 8–13, 2010. © 2010 Wiley‐Liss, Inc.     

Protease inhibitors: A panacea?

With the increasing evidence of protease involvement in several diseases, novel strategies for drug development involve the use of protease inhibitors (PIs). The local balance between protease inhibitors and proteases is an important determinant of the occurrence and progression of a particular disease. Hence, enzymes and their cognate inhibitors are finding their applications as diagnostic and prognostic markers. PIs are widely implicated for their use in host defense against infection, tissue repair and matrix production, blood coagulation, cancer, and they are, therefore, the current focus as therapeutic alternatives for major diseases such as AIDS and Alzheimer's diseases. This review is a brief summary of the varied role of protein protease inhibitors in controlling the activity of aberrant enzymes in several diseases afflicting mankind today. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:270–277, 2010; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.20335     

Mitochondria and Aging

Cover illustration: Mitochondria and Aging, a special issue edited by Professor Heinz D. Osiewacz (Frankfurt, Germany), devoted to aging research and the involvement of mitochondria “from models to humans”. Depicted are a 3D section of a human cell with mitochondria shown in red (© NIH, see http://ghr.nlm.nih.gov/handbook/illustrations/cellmitochondria) and from top to bottom: micrograph of mitochondria from the model organism Podospora anserina (© C. Scheckhuber, see p. 781), hand with pill (© Photodisc Inc.) and the worm Caenorhabditis elegans with typical senescent morphology (© B. Braeckman, see p. 803).     

Role of FGFs/FGFRs in skeletal development and bone regeneration

Fibroblast growth factor (FGF)/FGF (FGFR) signaling is an important pathway involved in skeletal development. Missense mutations in FGFs and FGFRs were found clinically to cause multiple congenital skeleton diseases including chondrodysplasia, craniosynostosis, syndromes with dysregulated phosphate metabolism. FGFs/FGFRs also have crucial roles in bone fracture repair and bone regeneration. Understanding the molecular mechanisms for the role of FGFs/FGFRs in the regulation of skeletal development, genetic skeletal diseases, and fracture healing will ultimately lead to better treatment of skeleton diseases caused by mutations of FGFs/FGFRs and fracture. This review summarizes the major findings on the role of FGF signaling in skeletal development, genetic skeletal diseases and bone healing, and discusses issues that remain to be resolved in applying FGF signaling‐related measures to promote bone healing. This review has also provided a perspective view on future work for exploring the roles and action mechanisms of FGF signaling in skeletal development, genetic skeletal diseases, and fracture healing. J. Cell. Physiol. 227: 3731–3743, 2012. © 2012 Wiley Periodicals, Inc.