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Sample records for exosomes current perspectives

  1. Proteomic profiling of exosomes: Current perspectives

    DEFF Research Database (Denmark)

    Simpson, Richard J; Jensen, Søren S; Lim, Justin W E

    2008-01-01

    distinct subsets of proteins that may be linked to cell-type associated functions. The secretion of exosomes by tumor cells and their implication in the transport and propagation of infectious cargo such as prions and retroviruses such as HIV suggest their participation in pathological situations...

  2. Exosomes in Critical Illness.

    Science.gov (United States)

    Terrasini, Nora; Lionetti, Vincenzo

    2017-06-01

    Exosomes are small, cell-released vesicles (40-100 nm in size) with the potential to transfer proteins, lipids, small RNAs, messenger RNAs, or DNA between cells via interstitial fluids. Due to their role in tissue homeostasis, exosomes have emerged as a new type of therapeutic and diagnostic (theranostic) tool in the noninvasive assessment of organ response to injury or treatment and in the development of reliable organ-protective intensive therapy. Our review provides current insights into the role of exosomes in the personalized management of injury and repair responses in critical illness. Data were obtained from a PubMed search of the most recent medical literature, including the PubMed "related articles" search methodology. Articles considered include original articles, review articles and conference proceedings. A detailed review of scientific, peer-reviewed data was performed. Relevant pre-clinical and clinical studies were included and summarized. Current scientific evidence is focused on the following: 1) Frontiers in the management of critical illness; 2) Biogenesis, characterization, and function of circulating exosomes; 3) The role of exosomes in acute lung injury; 4) The role of exosomes in acute cardiac injury; 5) The role of exosomes in acute kidney injury; 6) The role of exosomes in sepsis; 7) Limitations of exosome isolation protocols; and 8) Perspectives in the theranostic use of exosomes. Circulating levels of exosomes are associated with the onset and clinical course of critical illness. Exosomes released from cells with different phenotypes exert different functions in order to protect tissue and preserve organ function. Therefore, multifunctional exosomes with combined diagnostic and therapeutic functions show great promise in terms of personalized nanomedicine for patient-specific diagnosis and treatment of critical illness.

  3. Perspective Insights of Exosomes in Neurodegenerative Diseases: A Critical Appraisal

    Directory of Open Access Journals (Sweden)

    Arif Tasleem Jan

    2017-09-01

    Full Text Available Exosomes are small membranous entities of endocytic origin. Their production by a wide variety of cells in eukaryotes implicates their roles in the execution of essential processes, especially cellular communication. Exosomes are secreted under both physiological and pathophysiological conditions, and their actions on neighboring and distant cells lead to the modulations of cellular behaviors. They also assist in the delivery of disease causing entities, such as prions, α-syn, and tau, and thus, facilitate spread to non-effected regions and accelerate the progressions of neurodegenerative diseases. The characterization of exosomes, provides information on aberrant processes, and thus, exosome analysis has many clinical applications. Because they are associated with the transport of different cellular entities across the blood-brain barrier (BBB, exosomes might be useful for delivering drugs and other therapeutic molecules to brain. Herein, we review roles played by exosomes in different neurodegenerative diseases, and the possibilities of using them as diagnostic biomarkers of disease progression, drug delivery vehicles and in gene therapy.

  4. Perspective Insights of Exosomes in Neurodegenerative Diseases: A Critical Appraisal

    Science.gov (United States)

    Jan, Arif Tasleem; Malik, Mudasir A.; Rahman, Safikur; Yeo, Hye R.; Lee, Eun J.; Abdullah, Tasduq S.; Choi, Inho

    2017-01-01

    Exosomes are small membranous entities of endocytic origin. Their production by a wide variety of cells in eukaryotes implicates their roles in the execution of essential processes, especially cellular communication. Exosomes are secreted under both physiological and pathophysiological conditions, and their actions on neighboring and distant cells lead to the modulations of cellular behaviors. They also assist in the delivery of disease causing entities, such as prions, α-syn, and tau, and thus, facilitate spread to non-effected regions and accelerate the progressions of neurodegenerative diseases. The characterization of exosomes, provides information on aberrant processes, and thus, exosome analysis has many clinical applications. Because they are associated with the transport of different cellular entities across the blood-brain barrier (BBB), exosomes might be useful for delivering drugs and other therapeutic molecules to brain. Herein, we review roles played by exosomes in different neurodegenerative diseases, and the possibilities of using them as diagnostic biomarkers of disease progression, drug delivery vehicles and in gene therapy. PMID:29033828

  5. Hyperemesis gravidarum: current perspectives

    Science.gov (United States)

    McCarthy, Fergus P; Lutomski, Jennifer E; Greene, Richard A

    2014-01-01

    Hyperemesis gravidarum is a complex condition with a multifactorial etiology characterized by severe intractable nausea and vomiting. Despite a high prevalence, studies exploring underlying etiology and treatments are limited. We performed a literature review, focusing on articles published over the last 10 years, to examine current perspectives and recent developments in hyperemesis gravidarum. PMID:25125986

  6. Sustainable winegrowing: current perspectives

    Directory of Open Access Journals (Sweden)

    Mariani A

    2015-05-01

    Full Text Available Angela Mariani,1 Antonella Vastola2 1Department of Economic and Legal Studies, University Parthenope, Naples, 2School of Agricultural, Forestry, Food and Environmental Sciences, University of Basilicata, Potenza, Italy Abstract: The winegrowing sector worldwide is strongly committed to improving environmental and social sustainability. The aim of this work, based on a literature review, is to highlight current sustainability perspectives and the related main issues. There is a broad consensus that the challenge to achieve a greater spread of sustainable practices is to enhance environmental and social sustainability while maintaining economic viability. From the producers' point of view, the priority is to bridge the still substantial knowledge gaps in terms of perceived environmental benefits, economic benefits, and costs. Thus, an increased research effort focusing on the costs and benefits of different winegrowing practices and technical assistance with implementation might support their diffusion. Moreover, targeted marketing strategies are needed to: enhance consumers' involvement and their attitude toward sustainable wine; improve understanding and use of sustainable labels and claims; and raise awareness of some environmental credentials of wine packaging, mainly with reference to lightweight glass bottles. Keywords: winegrower, sustainability, wine, consumer, marketing strategies

  7. Atypical depression: current perspectives

    Directory of Open Access Journals (Sweden)

    Łojko D

    2017-09-01

    Full Text Available Dorota Łojko,1 Janusz K Rybakowski1,2 1Department of Adult Psychiatry, 2Department of Child and Adolescent Psychiatry, Poznan University of Medical Sciences, Poznan, Poland Abstract: The history and present status of the definition, prevalence, neurobiology, and treatment of atypical depression (AD is presented. The concept of AD has evolved through the years, and currently, in Diagnostic and Statistical Manual of Mental Disorders (DSM, Fifth Edition, the specifier of depressive episode with atypical feature is present for both diagnostic groups, that is, depressive disorders and bipolar and related disorders. This specifier includes mood reactivity, hyperphagia, hypersomnia, leaden paralysis, and interpersonal rejection sensitivity. Prevalence rates of AD are variable, depending on the criteria, methodology, and settings. The results of epidemiological studies using DSM criteria suggest that 15%–29% of depressed patients have AD, and the results of clinical studies point to a prevalence of 18%–36%. A relationship of AD with bipolar depression, seasonal depression, and obesity has also been postulated. Pathogenic research has been mostly focused on distinguishing AD from melancholic depression. The differences have been found in biochemical studies in the areas of hypothalamic–pituitary–adrenal axis, inflammatory markers, and the leptin system, although the results obtained are frequently controversial. A number of findings concerning such differences have also been obtained using neuroimaging and neurophysiological and neuropsychological methods. An initial concept of AD as a preferentially monoamine oxidase inhibitor-responsive depression, although confirmed in some further studies, is of limited use nowadays. Currently, despite numerous drug trials, there are no comprehensive treatment guidelines for AD. We finalize the article by describing the future research perspectives for the definition, neurobiology, and treatment. A better

  8. Atypical depression: current perspectives

    Science.gov (United States)

    Łojko, Dorota; Rybakowski, Janusz K

    2017-01-01

    The history and present status of the definition, prevalence, neurobiology, and treatment of atypical depression (AD) is presented. The concept of AD has evolved through the years, and currently, in Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition, the specifier of depressive episode with atypical feature is present for both diagnostic groups, that is, depressive disorders and bipolar and related disorders. This specifier includes mood reactivity, hyperphagia, hypersomnia, leaden paralysis, and interpersonal rejection sensitivity. Prevalence rates of AD are variable, depending on the criteria, methodology, and settings. The results of epidemiological studies using DSM criteria suggest that 15%–29% of depressed patients have AD, and the results of clinical studies point to a prevalence of 18%–36%. A relationship of AD with bipolar depression, seasonal depression, and obesity has also been postulated. Pathogenic research has been mostly focused on distinguishing AD from melancholic depression. The differences have been found in biochemical studies in the areas of hypothalamic–pituitary–adrenal axis, inflammatory markers, and the leptin system, although the results obtained are frequently controversial. A number of findings concerning such differences have also been obtained using neuroimaging and neurophysiological and neuropsychological methods. An initial concept of AD as a preferentially monoamine oxidase inhibitor-responsive depression, although confirmed in some further studies, is of limited use nowadays. Currently, despite numerous drug trials, there are no comprehensive treatment guidelines for AD. We finalize the article by describing the future research perspectives for the definition, neurobiology, and treatment. A better specification of diagnostic criteria and description of clinical picture, a genome-wide association study of AD, and establishing updated treatment recommendations for this clinical phenomenon should be

  9. MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment.

    Science.gov (United States)

    Toh, Wei Seong; Lai, Ruenn Chai; Hui, James Hoi Po; Lim, Sai Kiang

    2017-07-01

    Mesenchymal stem cell (MSC) therapies have demonstrated efficacy in cartilage repair in animal and clinical studies. The efficacy of MSC-based therapies which was previously predicated on the chondrogenic potential of MSC is increasingly attributed to the paracrine secretion, particularly exosomes. Exosomes are thought to function primarily as intercellular communication vehicles to transfer bioactive lipids, nucleic acids (mRNAs and microRNAs) and proteins between cells to elicit biological responses in recipient cells. For MSC exosomes, many of these biological responses translated to a therapeutic outcome in injured or diseased cells. Here, we review the current understanding of MSC exosomes, discuss the possible mechanisms of action in cartilage repair within the context of the widely reported immunomodulatory and regenerative potency of MSC exosomes, and provide new perspectives for development of an off-the-shelf and cell-free MSC therapy for treatment of cartilage injuries and osteoarthritis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Post-translational modifications of exosomal proteins.

    Science.gov (United States)

    Moreno-Gonzalo, Olga; Villarroya-Beltri, Carolina; Sánchez-Madrid, Francisco

    2014-01-01

    Exosomes mediate intercellular communication and participate in many cell processes such as cancer progression, immune activation or evasion, and the spread of infection. Exosomes are small vesicles secreted to the extracellular environment through the release of intraluminal vesicles contained in multivesicular bodies (MVBs) upon the fusion of these MVBs with the plasma membrane. The composition of exosomes is not random, suggesting that the incorporation of cargo into them is a regulated process. However, the mechanisms that control the sorting of protein cargo into exosomes are currently elusive. Here, we review the post-translational modifications detected in exosomal proteins, and discuss their possible role in their specific sorting into exosomes.

  11. Goldenhar syndrome: current perspectives.

    Science.gov (United States)

    Bogusiak, Katarzyna; Puch, Aleksandra; Arkuszewski, Piotr

    2017-10-01

    Progress in medical branches that has taken place since the first child with Goldenhare syndrome (GS) had been described in 1952 by Maurice Goldenhar, facilitated better understanding of this congenital defect. It also gave new perspectives and the opportunity to achieve satisfactory treatment results, mainly due to development of surgical techniques. Based on the literature and own experience, we discussed the phenotype of presentation of GS, ethiopathogenesis, genetic counselling and treatment with particular emphasis on surgery correction of hemifacial microsomia. The spectrum of GS abnormalities ranges from mild to severe ones and include patients with barely noticeable facial asymmetry to very pronounced facial defect with more or less severe abnormalities of internal organs and/or skeleton. It is characterized most commonly by impaired development of eyes, ears, lips, tongue, palate, mandible, maxilla, zygomatic and orbital structures and deformations of the teeth structures. Ethiopathogenesis is multifactorial and dependent on genetic and environmental factors but there are still many unknowns about the syndrome which should be revealed. Patients with GS due to a large variety of abnormalities and different severity of symptoms pose a challenge for clinicians. All of this necessitate an individual approach to each single patient and involvement a team of specialists in treatment planning. It is a complex, long-lasting, multidisciplinary process and should be divided into stages, according to patient's age, as well as the extent and severity of observed abnormalities. Neonatologists and pediatricians are involved in care of these patients from the onset.

  12. Exosomes as immunotheranostic nanoparticles.

    Science.gov (United States)

    Natasha G; Gundogan, Buket; Tan, Aaron; Farhatnia, Yasmin; Wu, Woffles; Rajadas, Jayakumar; Seifalian, Alexander M

    2014-06-01

    Exosomes are small biological membrane vesicles that measure 30 to 100 nm in diameter. They are involved in a wide array of biological activities, such as cell-cell communication, signal transduction, transport of genetic materials, and modulation of immune response. Evidence indicates that they can be used as not only therapeutic agents targeted against disease but also diagnostic biomarkers for pathologic conditions. In this review, we endeavor to present exosomes as immunologic agents that can be used as pioneering cancer vaccines to prime the immune system and explicate their therapeutic and diagnostic capabilities. An extensive literature search for studies that involved the use of exosomes as immunotheranostic nanoparticles was conducted using PubMed, ISI Web of Knowledge, and Google Scholar. Clinical trials that involved exosomes were also compiled by searching the clinicaltrials.gov database. In its therapeutic facet of application, exosomes can be used as vehicles for drug or gene delivery. These biological vesicles have been found to have excellent host biodistribution and biocompatibility, issues often presented with gene delivery vehicles. Diagnostically, exosomes may prove to be useful biomarkers that are able to surpass current setbacks of modern diagnostic testing, which include invasive methods. Finally, current evidence has implied that the use of exosomes could form the basis for the development of future cell-free cancer vaccines. Exosomes have numerous functions, and their double-edged features make the scope of their clinical applications, as both a diagnostic and therapeutic tool, immense. Crown Copyright © 2014. Published by EM Inc USA. All rights reserved.

  13. Exosomes as nucleic acid nanocarriers.

    Science.gov (United States)

    van den Boorn, Jasper G; Dassler, Juliane; Coch, Christoph; Schlee, Martin; Hartmann, Gunther

    2013-03-01

    Exosomes are nano-sized vesicles produced naturally by many cell types. They are specifically loaded with nucleic acid cargo, dependent on the exosome-producing cell and its homeostatic state. As natural intercellular shuttles of miRNA, exosomes influence an array of developmental, physiological and pathological processes in the recipient cell or tissue to which they can be selectively targeted by their tetraspanin surface-domains. By a review of current research, we illustrate here why exosomes are ideal nanocarriers for use in the targeted in vivo delivery of nucleic acids. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Uterine sarcoma ? current perspectives

    OpenAIRE

    Benson C; Miah AB

    2017-01-01

    Charlotte Benson,1 Aisha B Miah1,2 1Sarcoma Unit, Royal Marsden Hospital, 2Department of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK Abstract: Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiom...

  15. Acquired hypofibrinogenemia: current perspectives

    Directory of Open Access Journals (Sweden)

    Besser MW

    2016-09-01

    Full Text Available Martin W Besser,1 Stephen G MacDonald2 1Department of Haematology, 2Department of Specialist Haemostasis, The Pathology Partnership, Addenbrooke’s Hospital, Cambridge, UK Abstract: Acquired hypofibrinogenemia is most frequently caused by hemodilution and consumption of clotting factors. The aggressive replacement of fibrinogen has become one of the core principles of modern management of massive hemorrhage. The best method for determining the patient’s fibrinogen level remains controversial, and particularly in acquired dysfibrinogenemia, could have major therapeutic implications depending on which quantification method is chosen. This review introduces the available laboratory and point-of-care methods and discusses the relative advantages and limitations. It also discusses current strategies for the correction of hypofibrinogenemia. Keywords: Clauss fibrinogen assay, fibrinogen antigen, viscoelastic testing, ­gravimetric fibrinogen assay, PT-derived fibrinogen, functional fibrinogen, direct oral anticoagulant, dysfibrinogenemia, afibrinogenemia

  16. Provoked vestibulodynia: current perspectives.

    Science.gov (United States)

    Henzell, Helen; Berzins, Karen; Langford, Jennifer P

    2017-01-01

    Provoked vestibulodynia (PVD) refers to vulvar pain of at least 3 months duration, localized to the vestibule, provoked by touch and sexual activity and occurring in the absence of a clear identifiable cause. The clinical spectrum ranges from mild with distressing discomfort through to severe and disabling pain. Current understanding is that PVD is one of many chronic pain conditions characterized by sensitization of peripheral and central nociceptive pathways, with pain arising due to dysfunctional neuronal activity in the absence of painful stimuli. Pathophysiology is not well understood but is likely a complex interplay of environmental, genetic, psychological and immune factors. Care is multidisciplinary and follows general principles of chronic pain management with the addition of specific therapy tailored to address pelvic floor overactivity, and sexual and relationship difficulties. More recently, the therapeutic use of placebo is gaining traction in chronic pain research and is a very promising adjunctive therapy. The majority of women with PVD are managed outside of tertiary clinic settings, and care depends on availability and affordability of specialized services; however, much can be done by the primary health provider. PVD is common, and highly treatable, especially with early intervention, but unfortunately, many clinicians are unaware of this condition, and the biggest hurdle for women accessing treatment is obtaining a diagnosis. With treatment, most women can expect significant improvement, often with fairly simple interventions, although some women will benefit from referral to specialized centers. The aims of this article are twofold: firstly, to summarize current literature concerning PVD pathophysiology and management; secondly, to provide a framework for clinicians unfamiliar with vulvar medicine to understand and manage PVD.

  17. Provoked vestibulodynia: current perspectives

    Directory of Open Access Journals (Sweden)

    Henzell H

    2017-09-01

    Full Text Available Helen Henzell,1,2 Karen Berzins,1,3 Jennifer P Langford4 1Melbourne Sexual Health Centre, Carlton, 2Action Centre, Family Planning Victoria, Melbourne, 3Dermatology/Vulval Conditions Clinic, Mercy Hospital for Women, Heidelberg, 4Clifton Hill Physiotherapy, Clifton Hill, VIC, Australia Abstract: Provoked vestibulodynia (PVD refers to vulvar pain of at least 3 months duration, localized to the vestibule, provoked by touch and sexual activity and occurring in the absence of a clear identifiable cause. The clinical spectrum ranges from mild with distressing discomfort through to severe and disabling pain. Current understanding is that PVD is one of many chronic pain conditions characterized by sensitization of peripheral and central nociceptive pathways, with pain arising due to dysfunctional neuronal activity in the absence of painful stimuli. Pathophysiology is not well understood but is likely a complex interplay of environmental, genetic, psychological and immune factors. Care is multidisciplinary and follows general principles of chronic pain management with the addition of specific therapy tailored to address pelvic floor overactivity, and sexual and relationship difficulties. More recently, the therapeutic use of placebo is gaining traction in chronic pain research and is a very promising adjunctive therapy. The majority of women with PVD are managed outside of tertiary clinic settings, and care depends on availability and affordability of specialized services; however, much can be done by the primary health provider. PVD is common, and highly treatable, especially with early intervention, but unfortunately, many clinicians are unaware of this condition, and the biggest hurdle for women accessing treatment is obtaining a diagnosis. With treatment, most women can expect significant improvement, often with fairly simple interventions, although some women will benefit from referral to specialized centers. The aims of this article are twofold

  18. Misophonia: current perspectives

    Directory of Open Access Journals (Sweden)

    Cavanna AE

    2015-08-01

    Full Text Available Andrea E Cavanna,1–3 Stefano Seri3,4 1Department of Neuropsychiatry, Birmingham and Solihull Mental Health NHS Foundation Trust and University of Birmingham, Birmingham, 2Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, 3School of Life and Health Sciences, Aston Brain Centre, Wellcome Trust Laboratory for MEG Studies, Aston University, 4Children’s Epilepsy Surgery Programme, The Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, UK Abstract: Misophonia is characterized by a negative reaction to a sound with a specific pattern and meaning to a given individual. In this paper, we review the clinical features of this relatively common yet underinvestigated condition, with focus on co-occurring neurodevelopmental disorders. Currently available data on the putative pathophysiology of the condition can inform our understanding and guide the diagnostic process and treatment approach. Tinnitus retraining therapy and cognitive behavior therapy have been proposed as the most effective treatment strategies for reducing symptoms; however, current treatment algorithms should be validated in large population studies. At the present stage, competing paradigms see misophonia as a physiological state potentially inducible in any subject, an idiopathic condition (which can present with comorbid psychiatric disorders, or a symptomatic manifestation of an underlying psychiatric disorder. Agreement on the use of standardized diagnostic criteria would be an important step forward in terms of both clinical practice and scientific inquiry. Areas for future research include phenomenology, epidemiology, modulating factors, neurophysiological underpinnings, and treatment trials. Keywords: misophonia, selective sound sensitivity syndrome, hyperacusis, neurodevelopmental disorders, Tourette syndrome, obsessive-compulsive spectrum

  19. Provoked vestibulodynia: current perspectives

    Science.gov (United States)

    Henzell, Helen; Berzins, Karen; Langford, Jennifer P

    2017-01-01

    Provoked vestibulodynia (PVD) refers to vulvar pain of at least 3 months duration, localized to the vestibule, provoked by touch and sexual activity and occurring in the absence of a clear identifiable cause. The clinical spectrum ranges from mild with distressing discomfort through to severe and disabling pain. Current understanding is that PVD is one of many chronic pain conditions characterized by sensitization of peripheral and central nociceptive pathways, with pain arising due to dysfunctional neuronal activity in the absence of painful stimuli. Pathophysiology is not well understood but is likely a complex interplay of environmental, genetic, psychological and immune factors. Care is multidisciplinary and follows general principles of chronic pain management with the addition of specific therapy tailored to address pelvic floor overactivity, and sexual and relationship difficulties. More recently, the therapeutic use of placebo is gaining traction in chronic pain research and is a very promising adjunctive therapy. The majority of women with PVD are managed outside of tertiary clinic settings, and care depends on availability and affordability of specialized services; however, much can be done by the primary health provider. PVD is common, and highly treatable, especially with early intervention, but unfortunately, many clinicians are unaware of this condition, and the biggest hurdle for women accessing treatment is obtaining a diagnosis. With treatment, most women can expect significant improvement, often with fairly simple interventions, although some women will benefit from referral to specialized centers. The aims of this article are twofold: firstly, to summarize current literature concerning PVD pathophysiology and management; secondly, to provide a framework for clinicians unfamiliar with vulvar medicine to understand and manage PVD. PMID:28979166

  20. Vaginal rejuvenation: current perspectives

    Directory of Open Access Journals (Sweden)

    Barbara G

    2017-07-01

    Full Text Available Giussy Barbara,1 Federica Facchin,2 Laura Buggio,3 Daniela Alberico,3 Maria Pina Frattaruolo,3 Alessandra Kustermann1 1Department of Obstetrics and Gynecology, Service for Sexual and Domestic Violence (SVSeD, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, 2Faculty of Psychology, Catholic University of Milan, 3Department of Obstetrics and Gynecology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy Abstract: Female genital cosmetic surgery includes several procedures aimed at reaching better female genital appearance and/or improved sexual functioning. Among these procedures, vaginal rejuvenation is considered as one of the most controversial genital cosmetic surgical interventions and involves a range of surgical procedures performed by gynecologists or plastic surgeons to decrease the average diameter of the vagina, mainly for sexual reasons. In this narrative review, vaginal rejuvenation outcomes are examined in order to clarify the current scenario of the different vaginal rejuvenation techniques, as well as their effectiveness and associated complications. Psychological and ethical issues linked to these procedures are also addressed. Keywords: vaginal rejuvenation, female genital cosmetic surgery, vaginoplasty 

  1. Adjustment disorder: current perspectives

    Directory of Open Access Journals (Sweden)

    Zelviene P

    2018-01-01

    Full Text Available Paulina Zelviene, Evaldas Kazlauskas Department of Clinical and Organizational Psychology, Vilnius University, Vilnius, Lithuania Abstract: Adjustment disorder (AjD is among the most often diagnosed mental disorders in clinical practice. This paper reviews current status of AjD research and discusses scientific and clinical issues associated with AjD. AjD has been included in diagnostic classifications for over 50 years. Still, the diagnostic criteria for AjD remain vague and cause difficulties to mental health professionals. Controversies in definition resulted in the lack of reliable and valid measures of AjD. Epidemiological data on prevalence of AjD is scarce and not reliable because prevalence data are biased by the diagnostic algorithm, which is usually developed for each study, as no established diagnostic standards for AjD are available. Considerable changes in the field of AjD could follow after the release of the 11th edition of International Classification of Diseases (ICD-11. A new AjD symptom profile was introduced in ICD-11 with 2 main symptoms as follows: 1 preoccupation and 2 failure to adapt. However, differences between the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and ICD-11 AjD diagnostic criteria could result in diverse research findings in the future. The best treatment approach for AjD remains unclear, and further treatment studies are needed to provide AjD treatment guidelines to clinicians. Keywords: adjustment disorder, review, diagnosis, prevalence, treatment, DSM, ICD

  2. Current perspectives on preeclampsia.

    Science.gov (United States)

    Roberts, J

    1994-01-01

    The early recognition of elevated blood pressure in pregnancy is still considered the most critical step in preventing the maternal and perinatal morbidity and mortality associated with preeclampsia-eclampsia. The recognition of hypertension is enhanced by an initial assessment of a women's risk for developing high blood pressure during pregnancy, correct blood pressure measurement, and early prenatal care. The care of the woman with hypertension preceding a pregnancy or during a previous pregnancy includes not only early prenatal care but also pre- or interconceptual care that might minimize the risk of further blood pressure elevation during pregnancy, as well as later in life. Tests to predict preeclampsia, such as the "roll" test and the use of the mean arterial pressure during midpregnancy, have been found to be invalid because of poor predictive validity. Relative increases in blood pressure during pregnancy are also no longer considered diagnostic for preeclampsia, however, consideration of relative increases is still "prudent" in assessing signs and symptoms of this disease. The development of preeclampsia is thought to occur very early in pregnancy as a result of imbalances between vasoconstrictive and vasodilatory factors, probably accompanying implantation and placentation. The use of aspirin to prevent the development of hypertension and preeclampsia is currently being studied because it has been shown to shift the balance toward the metabolism of the vasodilatory prostaglandin, prostacycline. At this time, aspirin is only advised for women at high risk for developing preeclampsia. Calcium may also be a preventative mineral, and a diet that is adequate during pregnancy is advised.

  3. [Exosome: Trojan horse in immunotherapy].

    Science.gov (United States)

    Mou, Dan-Lei; Jia, Zhan-Sheng; Bai, Xue-Fan

    2005-04-01

    Exosomes are small membrane-bound vesicles that are secreted by a multitude of eukaryocytes as a consequence of fusion of multivesicular bodies with the plasma membrane. Exosomes can play critical roles in different physiological processes depending on their origins. Exosomes secreted from professional antigen-presenting cells are enriched in MHC class I and II complexes, costimulatory molecules, hsp 70 and hsp 90 chaperones, therefore exosomes, like Trojan horse, are of importance of immunoregulation in vivo and in vitro. The review will present current trends of research on the fundamental properties, production and purification of exosomes, and will focus on their implementation in cancer and virus immunotherapy as a novel cell-free peptide-based vaccine.

  4. Stem cell-derived exosomes: A promising strategy for fracture healing.

    Science.gov (United States)

    Hao, Zi-Chen; Lu, Jun; Wang, Shan-Zheng; Wu, Hao; Zhang, Yun-Tong; Xu, Shuo-Gui

    2017-10-01

    To describe the biological characteristics of exosomes and to summarize the current status of stem cell-derived exosomes on fracture healing. Meanwhile, future challenges, limitations and perspectives are also discussed. Search and analyze the related articles in pubmed database through the multi-combination of keywords like "stem cells","exosomes","bone regeneration" and "fracture healing". Stem cell-derived exosome therapy for fracture healing has been enjoying popularity and is drawing increasing attention. This strategy helps to promote proliferation and migration of cells, as well as osteogenesis and angiogenesis, in the process of bone formation. Although the exact mechanisms remain elusive, exosomal miRNAs seem to play vital roles. Future studies are required to solve multiple problems before clinical application, including comprehensive and thorough understanding of exosomes, the exact roles of exosomes in regulating bone formation, and the optimal source, dose and frequency of treatment, as well as technical and safety issues. Moreover, studies based on fracture models of large animals are could offer guidance and are in demand. © 2017 John Wiley & Sons Ltd.

  5. Internet gaming addiction: current perspectives

    Directory of Open Access Journals (Sweden)

    Kuss DJ

    2013-11-01

    Full Text Available Daria J KussPsychology Research and Behavior Management, Birmingham City University, Birmingham, UKAbstract: In the 2000s, online games became popular, while studies of Internet gaming addiction emerged, outlining the negative consequences of excessive gaming, its prevalence, and associated risk factors. The establishment of specialized treatment centers in South-East Asia, the US, and Europe reflects the growing need for professional help. It is argued that only by understanding the appeal of Internet gaming, its context, and neurobiologic correlates can the phenomenon of Internet gaming addiction be understood comprehensively. The aim of this review is to provide an insight into current perspectives on Internet gaming addiction using a holistic approach, taking into consideration the mass appeal of online games, the context of Internet gaming addiction, and associated neuroimaging findings, as well as the current diagnostic framework adopted by the American Psychiatric Association. The cited research indicates that the individual's context is a significant factor that marks the dividing line between excessive gaming and gaming addiction, and the game context can gain particular importance for players, depending on their life situation and gaming preferences. Moreover, the cultural context is significant because it embeds the gamer in a community with shared beliefs and practices, endowing their gaming with particular meaning. The cited neuroimaging studies indicate that Internet gaming addiction shares similarities with other addictions, including substance dependence, at the molecular, neurocircuitry, and behavioral levels. The findings provide support for the current perspective of understanding Internet gaming addiction from a disease framework. The benefits of an Internet gaming addiction diagnosis include reliability across research, destigmatization of individuals, development of efficacious treatments, and the creation of an incentive

  6. Internet gaming addiction: current perspectives

    Science.gov (United States)

    Kuss, Daria J

    2013-01-01

    In the 2000s, online games became popular, while studies of Internet gaming addiction emerged, outlining the negative consequences of excessive gaming, its prevalence, and associated risk factors. The establishment of specialized treatment centers in South-East Asia, the US, and Europe reflects the growing need for professional help. It is argued that only by understanding the appeal of Internet gaming, its context, and neurobiologic correlates can the phenomenon of Internet gaming addiction be understood comprehensively. The aim of this review is to provide an insight into current perspectives on Internet gaming addiction using a holistic approach, taking into consideration the mass appeal of online games, the context of Internet gaming addiction, and associated neuroimaging findings, as well as the current diagnostic framework adopted by the American Psychiatric Association. The cited research indicates that the individual’s context is a significant factor that marks the dividing line between excessive gaming and gaming addiction, and the game context can gain particular importance for players, depending on their life situation and gaming preferences. Moreover, the cultural context is significant because it embeds the gamer in a community with shared beliefs and practices, endowing their gaming with particular meaning. The cited neuroimaging studies indicate that Internet gaming addiction shares similarities with other addictions, including substance dependence, at the molecular, neurocircuitry, and behavioral levels. The findings provide support for the current perspective of understanding Internet gaming addiction from a disease framework. The benefits of an Internet gaming addiction diagnosis include reliability across research, destigmatization of individuals, development of efficacious treatments, and the creation of an incentive for public health care and insurance providers. The holistic approach adopted here not only highlights empirical research that

  7. Internet gaming addiction: current perspectives.

    Science.gov (United States)

    Kuss, Daria J

    2013-01-01

    In the 2000s, online games became popular, while studies of Internet gaming addiction emerged, outlining the negative consequences of excessive gaming, its prevalence, and associated risk factors. The establishment of specialized treatment centers in South-East Asia, the US, and Europe reflects the growing need for professional help. It is argued that only by understanding the appeal of Internet gaming, its context, and neurobiologic correlates can the phenomenon of Internet gaming addiction be understood comprehensively. The aim of this review is to provide an insight into current perspectives on Internet gaming addiction using a holistic approach, taking into consideration the mass appeal of online games, the context of Internet gaming addiction, and associated neuroimaging findings, as well as the current diagnostic framework adopted by the American Psychiatric Association. The cited research indicates that the individual's context is a significant factor that marks the dividing line between excessive gaming and gaming addiction, and the game context can gain particular importance for players, depending on their life situation and gaming preferences. Moreover, the cultural context is significant because it embeds the gamer in a community with shared beliefs and practices, endowing their gaming with particular meaning. The cited neuroimaging studies indicate that Internet gaming addiction shares similarities with other addictions, including substance dependence, at the molecular, neurocircuitry, and behavioral levels. The findings provide support for the current perspective of understanding Internet gaming addiction from a disease framework. The benefits of an Internet gaming addiction diagnosis include reliability across research, destigmatization of individuals, development of efficacious treatments, and the creation of an incentive for public health care and insurance providers. The holistic approach adopted here not only highlights empirical research that

  8. Biofield Science: Current Physics Perspectives.

    Science.gov (United States)

    Kafatos, Menas C; Chevalier, Gaétan; Chopra, Deepak; Hubacher, John; Kak, Subhash; Theise, Neil D

    2015-11-01

    This article briefly reviews the biofield hypothesis and its scientific literature. Evidence for the existence of the biofield now exists, and current theoretical foundations are now being developed. A review of the biofield and related topics from the perspective of physical science is needed to identify a common body of knowledge and evaluate possible underlying principles of origin of the biofield. The properties of such a field could be based on electromagnetic fields, coherent states, biophotons, quantum and quantum-like processes, and ultimately the quantum vacuum. Given this evidence, we intend to inquire and discuss how the existence of the biofield challenges reductionist approaches and presents its own challenges regarding the origin and source of the biofield, the specific evidence for its existence, its relation to biology, and last but not least, how it may inform an integrated understanding of consciousness and the living universe.

  9. Female pattern alopecia: current perspectives

    Directory of Open Access Journals (Sweden)

    Levy LL

    2013-08-01

    Full Text Available Lauren L Levy, Jason J Emer Department of Dermatology, Mount Sinai School of Medicine, New York, NY, USA Abstract: Hair loss is a commonly encountered problem in clinical practice, with men presenting with a distinctive pattern involving hairline recession and vertex balding (Norwood-Hamilton classification and women exhibiting diffuse hair thinning over the crown (increased part width and sparing of the frontal hairline (Ludwig classification. Female pattern hair loss has a strikingly overwhelming psychological effect; thus, successful treatments are necessary. Difficulty lies in successful treatment interventions, as only two medications – minoxidil and finasteride – are approved for the treatment of androgenetic alopecia, and these medications offer mediocre results, lack of a permanent cure, and potential complications. Hair transplantation is the only current successful permanent option, and it requires surgical procedures. Several other medical options, such as antiandrogens (eg, spironolactone, oral contraceptives, cyproterone, flutamide, dutasteride, prostaglandin analogs (eg, bimatoprost, latanoprost, and ketoconazole are reported to be beneficial. Laser and light therapies have also become popular despite the lack of a profound benefit. Management of expectations is crucial, and the aim of therapy, given the current therapeutic options, is to slow or stop disease progression with contentment despite patient expectations of permanent hair regrowth. This article reviews current perspectives on therapeutic options for female pattern hair loss. Keywords: androgenetic alopecia, female pattern hair loss, minoxidil, finasteride, antiandrogens, spironolactone

  10. Current perspectives on cognitive diversity

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    Andrea eBender

    2016-04-01

    Full Text Available To what extent is cognition influenced by a person’s cultural background? This question has remained controversial in large fields of the cognitive sciences, including cognitive psychology, and is also underexplored in anthropology. In this perspective article, findings from a recent wave of cross-cultural studies will be outlined with respect to three aspects of cognition: perception and categorization, number representation and counting, and explanatory frameworks and beliefs. Identifying similarities and differences between these domains allows for general conclusions regarding cognitive diversity and helps to highlight the importance of culturally shaped content for a comprehensive understanding of cognition.

  11. A Current Perspective on Photocatalysis

    Energy Technology Data Exchange (ETDEWEB)

    Fujita, E.; Muckerman, J.T.; Domen, K.

    2011-02-18

    of ChemSusChem is devoted to providing a current perspective on the field of photocatalysis. It contains invited papers from leading researchers in a wide range of important aspects of the field that address materials, photophysical, photochemical, and electrocatalysis issues. The area remains primarily the domain of basic research studies because progress toward the promise offered by the early work has (at least until recently) been slow, despite its significance having become increasingly recognized. The present collection of papers deals with new semiconductor photocatalysts, molecular catalysts for hydrogen production and water oxidation, dye-sensitized photoelectrochemical cells, and electrochemical CO{sub 2} reduction. Overall photochemical water splitting without any applied bias potential is achieved in several systems, especially under UV irradiation. Further advances are also achieved in a few semiconductor systems, such as GaZn oxynitrides or two-step (so-called 'Z-scheme') systems to produce H{sub 2} and O{sub 2} without any sacrificial reagent under visible irradiation. When band gaps of semiconductors are narrowed to absorb more visible light for greater efficiency, or when band positions are not suitable for carrying out one-electron redox processes, multielectron catalysts are required to promote proton-coupled electron transfer reactions in producing solar fuels. In homogeneous photocatalysis systems, sacrificial reagents are typically used to investigate the catalytic activity, detailed kinetics, and mechanisms of a half reaction. Photoelectrolysis systems with immobilized catalysts (metals, metal oxides, or molecular catalysts) on electrodes can separate oxidized products, such as O{sub 2}, and reduced products, such as H{sub 2}, CO, CH{sub 3}OH, and others, by means of proton- or hydroxide-conducting membranes. The following paragraphs briefly summarize these contributions. In the area of UV-driven water splitting, Townsend et al

  12. Prospects for exosomes in immunotherapy of cancer

    Science.gov (United States)

    Mignot, G; Roux, S; Thery, Clotilde; Ségura, Elodie; Zitvogel, L

    2006-01-01

    Exosomes are nanometer sized membrane vesicles invaginating from multivesicular bodies and secreted from epithelial and hematopoietic cells. They were first described “in vitro” but vesicles with the hallmarks of exosomes are present in vivo in germinal centers and biological fluids. Their protein and lipid composition are unique and could account for their expanding functions such as eradication of obsolete proteins, antigen presentation or “Trojan horses” for viruses or prions. Exosome secretion could be a regulated process participating in the transfer of molecules inbetween immune cells. Despite numerous questions pertaining to their biological relevance, the potential of dendritic cell derived-exosomes as cell-free cancer vaccines is currently being assessed. This review will summarize the composition and formation of exosomes, preclinical data, Phase I trials and optimization protocols for improving their immunogenicity in tumor bearing patients. PMID:16796806

  13. Preventing dance injuries: current perspectives

    Science.gov (United States)

    Russell, Jeffrey A

    2013-01-01

    Dancers are clearly athletes in the degree to which sophisticated physical capacities are required to perform at a high level. The standard complement of athletic attributes – muscular strength and endurance, anaerobic and aerobic energy utilization, speed, agility, coordination, motor control, and psychological readiness – all are essential to dance performance. In dance, as in any athletic activity, injuries are prevalent. This paper presents the research background of dance injuries, characteristics that distinguish dance and dancers from traditional sports and athletes, and research-based perspectives into how dance injuries can be reduced or prevented, including the factors of physical training, nutrition and rest, flooring, dancing en pointe, and specialized health care access for dancers. The review concludes by offering five essential components for those involved with caring for dancers that, when properly applied, will assist them in decreasing the likelihood of dance-related injury and ensuring that dancers receive optimum attention from the health care profession: (1) screening; (2) physical training; (3) nutrition and rest; (4) specialized dance health care; and (5) becoming acquainted with the nature of dance and dancers. PMID:24379726

  14. Preventing dance injuries: current perspectives

    Directory of Open Access Journals (Sweden)

    Russell JA

    2013-09-01

    Full Text Available Jeffrey A Russell Division of Athletic Training, School of Applied Health Sciences and Wellness, Ohio University, Athens, OH, USA Abstract: Dancers are clearly athletes in the degree to which sophisticated physical capacities are required to perform at a high level. The standard complement of athletic attributes – muscular strength and endurance, anaerobic and aerobic energy utilization, speed, agility, coordination, motor control, and psychological readiness – all are essential to dance performance. In dance, as in any athletic activity, injuries are prevalent. This paper presents the research background of dance injuries, characteristics that distinguish dance and dancers from traditional sports and athletes, and research-based perspectives into how dance injuries can be reduced or prevented, including the factors of physical training, nutrition and rest, flooring, dancing en pointe, and specialized health care access for dancers. The review concludes by offering five essential components for those involved with caring for dancers that, when properly applied, will assist them in decreasing the likelihood of dance-related injury and ensuring that dancers receive optimum attention from the health care profession: (1 screening; (2 physical training; (3 nutrition and rest; (4 specialized dance health care; and (5 becoming acquainted with the nature of dance and dancers. Keywords: dance, injuries, injury prevention, fitness, wellness, health

  15. Adolescent idiopathic scoliosis: current perspectives

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    Miyanji F

    2014-01-01

    Full Text Available Firoz MiyanjiBritish Columbia Children's Hospital, Vancouver, BC, CanadaAbstract: Adolescent idiopathic scoliosis (AIS remains a common and potentially severe musculoskeletal disorder. Although its etiology is largely unknown, ongoing research endeavors continue to improve our understanding of its potential origin and its natural history. Advances in understanding its true three-dimensional nature have sought to improve classification and management strategies. This review will attempt to highlight and give an overview of the current concepts in adolescent idiopathic scoliosis.Keywords: AIS, current, natural history, management strategies

  16. Contralateral prophylactic mastectomy: current perspectives

    Directory of Open Access Journals (Sweden)

    Yao K

    2016-06-01

    Full Text Available Katharine Yao,1 Mark Sisco,2 Isabelle Bedrosian3 1Division of Surgical Oncology, Department of Surgery, 2Division of Plastic Surgery, Department of Surgery, NorthShore University HealthSystem, Evanston, IL, 3Department of Surgery, MD Anderson Cancer Center, Houston, TX, USA Abstract: There has been an increasing trend in the use of contralateral prophylactic mastectomy (CPM in the United States among women diagnosed with unilateral breast cancer, particularly young women. Approximately one-third of women ,40 years old are undergoing CPM in the US. Most studies have shown that the CPM trend is mainly patient-driven, which reflects a changing environment for newly diagnosed breast cancer patients. The most common reason that women choose CPM is based on misperceptions about CPM’s effect on survival and overestimation of their contralateral breast cancer (CBC risk. No prospective studies have shown survival benefit to CPM, and the CBC rate for most women is low at 10 years. Fear of recurrence is also a big driver of CPM decisions. Nonetheless, studies have shown that women are mostly satisfied with undergoing CPM, but complications and subsequent surgeries with reconstruction have been associated with dissatisfaction with CPM. Studies on surgeon’s perspectives on CPM are sparse but show that the most common reasons surgeons discuss CPM with patients is because of a suspicious family history or for a patient who is a confirmed BRCA mutation carrier. Studies on the cost–effectiveness of CPM have been conflicting and are highly dependent on patient’s quality of life after CPM. Most recent guidelines for CPM are contradictory. Future areas of research include the development of interventions to better inform patients about CPM, modification of the guidelines to form a more consistent statement, longer term studies on CBC risk and CPM’s effect on survival, and prospective studies that track the psychosocial effects of CPM on body image and

  17. Botrytized wines – current perspectives

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    Magyar I

    2016-10-01

    Full Text Available Ildikó Magyar, János Soós Department of Oenology, Institute of Viticulture and Oenology, Szent István University, Budapest, Hungary Abstract: Botrytized wines are wine specialties made of overripe grapes infected by Botrytis cinerea with the form “noble rot”. Due to the particular characteristics of the noble rotted grape, these wines (eg, Tokaji Aszú, Sauternes, Trockenbeerenauslese types, etc have many characteristic features, including higher or lower residual sugar content and unique aroma composition. The technology, biochemistry, and special characteristics of botrytized wines have been researched for a long time. This review outlines the main directions of the current studies, giving a brief overview on the recent findings. Beside the traditional wine types, noble rot is increasingly utilized in making newer sweet wine styles and straw (passito wines, which generates a series of new interesting experimental results. The fungus–grape interactions during the noble rot, the induced botrytization, the microbial communities of botrytized wines, and the volatile compounds having key roles in the distinct aroma of these wine styles are being focused on in the current studies in this field. Keywords: Botrytis, noble rot, sweet wines, passito wine, aroma

  18. Collagen cross linking: Current perspectives

    Directory of Open Access Journals (Sweden)

    Srinivas K Rao

    2013-01-01

    Full Text Available Keratoconus is a common ectatic disorder occurring in more than 1 in 1,000 individuals. The condition typically starts in adolescence and early adulthood. It is a disease with an uncertain cause and its progression is unpredictable, but in extreme cases, vision deteriorates and can require corneal transplant surgery. Corneal collagen cross-linking (CCL with riboflavin (C3R is a recent treatment option that can enhance the rigidity of the cornea and prevent disease progression. Since its inception, the procedure has evolved with newer instrumentation, surgical techniques, and is also now performed for expanded indications other than keratoconus. With increasing experience, newer guidelines regarding optimization of patient selection, the spectrum of complications and their management, and combination procedures are being described. This article in conjunction with the others in this issue, will try and explore the uses of collagen cross-linking (CXL in its current form.

  19. Arsenic and diabetes: current perspectives.

    Science.gov (United States)

    Huang, Chun Fa; Chen, Ya Wen; Yang, Ching Yao; Tsai, Keh Sung; Yang, Rong Sen; Liu, Shing Hwa

    2011-09-01

    Arsenic is a naturally occurring toxic metalloid of global concern. Many studies have indicated a dose-response relationship between accumulative arsenic exposure and the prevalence of diabetes mellitus (DM) in arseniasis-endemic areas in Taiwan and Bangladesh, where arsenic exposure occurs through drinking water. Epidemiological researches have suggested that the characteristics of arsenic-induced DM observed in arseniasis-endemic areas in Taiwan and Mexico are similar to those of non-insulin-dependent DM (Type 2 DM). These studies analyzed the association between high and chronic exposure to inorganic arsenic in drinking water and the development of DM, but the effect of exposure to low to moderate levels of inorganic arsenic on the risk of DM is unclear. Navas-Acien et al. recently proposed that a positive association existed between total urine arsenic and the prevalence of Type 2 DM in people exposed to low to moderate levels of arsenic. However, the diabetogenic role played by arsenic is still debated upon. An increase in the prevalence of DM has been observed among residents of highly arsenic-contaminated areas, whereas the findings from community-based and occupational studies in low-arsenic-exposure areas have been inconsistent. Recently, a population-based cross-sectional study showed that the current findings did not support an association between arsenic exposure from drinking water at levels less than 300 μg/L and a significantly increased risk of DM. Moreover, although the precise mechanisms for the arsenic-induced diabetogenic effect are still largely undefined, recent in vitro experimental studies indicated that inorganic arsenic or its metabolites impair insulin-dependent glucose uptake or glucose-stimulated insulin secretion. Nevertheless, the dose, the form of arsenic used, and the experimental duration in the in vivo studies varied greatly, leading to conflicting results and ambiguous interpretation of these data with respect to human exposure

  20. Arsenic and diabetes: Current perspectives

    Directory of Open Access Journals (Sweden)

    Chun Fa Huang

    2011-09-01

    Full Text Available Arsenic is a naturally occurring toxic metalloid of global concern. Many studies have indicated a dose–response relationship between accumulative arsenic exposure and the prevalence of diabetes mellitus (DM in arseniasis-endemic areas in Taiwan and Bangladesh, where arsenic exposure occurs through drinking water. Epidemiological researches have suggested that the characteristics of arsenic-induced DM observed in arseniasis-endemic areas in Taiwan and Mexico are similar to those of non-insulin-dependent DM (Type 2 DM. These studies analyzed the association between high and chronic exposure to inorganic arsenic in drinking water and the development of DM, but the effect of exposure to low to moderate levels of inorganic arsenic on the risk of DM is unclear. Navas-Acien et al. recently proposed that a positive association existed between total urine arsenic and the prevalence of Type 2 DM in people exposed to low to moderate levels of arsenic. However, the diabetogenic role played by arsenic is still debated upon. An increase in the prevalence of DM has been observed among residents of highly arsenic-contaminated areas, whereas the findings from community-based and occupational studies in low-arsenic-exposure areas have been inconsistent. Recently, a population-based cross-sectional study showed that the current findings did not support an association between arsenic exposure from drinking water at levels less than 300 μg/L and a significantly increased risk of DM. Moreover, although the precise mechanisms for the arsenic-induced diabetogenic effect are still largely undefined, recent in vitro experimental studies indicated that inorganic arsenic or its metabolites impair insulin-dependent glucose uptake or glucose-stimulated insulin secretion. Nevertheless, the dose, the form of arsenic used, and the experimental duration in the in vivo studies varied greatly, leading to conflicting results and ambiguous interpretation of these data with

  1. Current Perspectives in Cardiac Laterality

    Directory of Open Access Journals (Sweden)

    Marina Campione

    2016-12-01

    Full Text Available The heart is the first organ to break symmetry in the developing embryo and onset of dextral looping is the first indication of this event. Looping is a complex process that progresses concomitantly to cardiac chamber differentiation and ultimately leads to the alignment of the cardiac regions in their final topology. Generation of cardiac asymmetry is crucial to ensuring proper form and consequent functionality of the heart, and therefore it is a highly regulated process. It has long been known that molecular left/right signals originate far before morphological asymmetry and therefore can direct it. The use of several animal models has led to the characterization of a complex regulatory network, which invariably converges on the Tgf-β signaling molecule Nodal and its downstream target, the homeobox transcription factor Pitx2. Here, we review current data on the cellular and molecular bases of cardiac looping and laterality, and discuss the contribution of Nodal and Pitx2 to these processes. A special emphasis will be given to the morphogenetic role of Pitx2 and to its modulation of transcriptional and functional properties, which have also linked laterality to atrial fibrillation.

  2. Longitudinal sleeve gastrectomy: current perspectives

    Directory of Open Access Journals (Sweden)

    Soricelli E

    2014-05-01

    Full Text Available Emanuele Soricelli, Giovanni Casella, Giorgio Di Rocco, Adriano Redler, Nicola BassoDepartment of Surgical Sciences, Policlinico Umberto I, Sapienza, University of Rome, ItalyAbstract: Since the early 2000s, laparoscopic sleeve gastrectomy has increasingly gained consensus in bariatric surgery, thanks to good to excellent results in terms of weight loss and comorbidity resolution, and to simpler technical aspects than in Roux-en-Y gastric bypass and biliopancreatic diversion. In yearly consensus summits, surgical indications, technical details, and management of complications, together with continuous update of data concerning clinical outcome, have been debated on the basis of increasing collective experience. In experimental studies and clinical trials, the pathophysiological mechanisms of weight loss and remission of cardiometabolic comorbidities subsequent to sleeve gastrectomy have been extensively discussed. The aim of this paper is to offer a review of state of the art laparoscopic sleeve gastrectomy and to focus attention on the currently most debated topics and future prospects of this procedure.Keywords: sleeve gastrectomy, type 2 diabetes mellitus, gastroesophageal reflux disease, revisional, quality of life

  3. Uterine sarcoma – current perspectives

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    Benson C

    2017-08-01

    Full Text Available Charlotte Benson,1 Aisha B Miah1,2 1Sarcoma Unit, Royal Marsden Hospital, 2Department of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK Abstract: Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiomyosarcoma is the most common sarcoma, but other subtypes include endometrial stromal sarcoma (low grade and high grade, undifferentiated uterine sarcoma and adenosarcoma. Clinical trials have shown no definite survival benefit of adjuvant radiotherapy or chemotherapy and have been hampered by the rarity and heterogeneity of these disease types. There is a role of adjuvant treatment in carefully selected cases following multidisciplinary discussion at sarcoma reference centers. In patients with metastatic disease, systemic chemotherapy can then be considered. There is activity of a number of agents, including doxorubicin, trabectedin, gemcitabine-based chemotherapy, eribulin and pazopanib. Patients should be considered for clinical trial entry where possible. Close international collaboration is important to allow progress in this group of diseases. Keywords: sarcoma, leiomyosarcoma, endometrial stromal sarcoma, undifferentiated uterine sarcoma, leiomyoma

  4. Selective laser trabeculoplasty: current perspectives

    Directory of Open Access Journals (Sweden)

    Leahy KE

    2015-05-01

    Full Text Available Kate E Leahy,1 Andrew JR White1–3 1Westmead Hospital, Westmead, NSW, Australia; 2Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Sydney, NSW, Australia; 3Save Sight Institute, University of Sydney, Sydney, NSW, Australia Abstract: Selective laser trabeculoplasty (SLT has been used in the treatment of glaucoma for just over a decade. Here, we review the current literature in terms of suggested mechanism, efficacy, method of treatment, predictors of success, adverse events, repeatability, and cost of SLT. The exact mechanism by which SLT lowers intraocular pressure (IOP remains unknown although circumstantial evidence has come in many forms in relation to structural alteration; oxidative stress and inflammatory responses; tight junction integrity; proliferative responses; and microbubble formation. SLT is as effective as argon laser trabeculoplasty and medications in reducing IOP in glaucoma and ocular hypertension. The treatment is not uniformly effective in all eyes, and its IOP-lowering effect decreases over time. High pretreatment IOP is the strongest predictor of success; however, significant pressure reduction has also been shown in normal-tension glaucoma and in patients already taking multiple antiglaucoma drops. Mild, transient adverse effects are common. Transient IOP spikes usually resolve quickly with or without antiglaucoma treatment but may be problematic in pigmented angles. The limited available evidence suggests SLT is repeatable and cost-effective for the treatment of glaucoma and ocular hypertension. Keywords: glaucoma, SLT, ocular hypertension, intraocular pressure

  5. Recurrent pregnancy loss: current perspectives

    Directory of Open Access Journals (Sweden)

    El Hachem H

    2017-05-01

    Full Text Available Hady El Hachem,1,2 Vincent Crepaux,3 Pascale May-Panloup,4 Philippe Descamps,3 Guillaume Legendre,3 Pierre-Emmanuel Bouet3 1Department of Reproductive Medicine, Ovo Clinic, Montréal, QC, Canada; 2Department of Obstetrics and Gynecology, University of Montreal, Montréal, QC, Canada; 3Department of Obstetrics and Gynecology, Angers University Hopsital, Angers, France; 4Department of Reproductive Biology, Angers University Hospital, Angers, France Abstract: Recurrent pregnancy loss is an important reproductive health issue, affecting 2%–5% of couples. Common established causes include uterine anomalies, antiphospholipid syndrome, hormonal and metabolic disorders, and cytogenetic abnormalities. Other etiologies have been proposed but are still considered controversial, such as chronic endometritis, inherited thrombophilias, luteal phase deficiency, and high sperm DNA fragmentation levels. Over the years, evidence-based treatments such as surgical correction of uterine anomalies or aspirin and heparin for antiphospholipid syndrome have improved the outcomes for couples with recurrent pregnancy loss. However, almost half of the cases remain unexplained and are empirically treated using progesterone supplementation, anticoagulation, and/or immunomodulatory treatments. Regardless of the cause, the long-term prognosis of couples with recurrent pregnancy loss is good, and most eventually achieve a healthy live birth. However, multiple pregnancy losses can have a significant psychological toll on affected couples, and many efforts are being made to improve treatments and decrease the time needed to achieve a successful pregnancy. This article reviews the established and controversial etiologies, and the recommended therapeutic strategies, with a special focus on unexplained recurrent pregnancy losses and the empiric treatments used nowadays. It also discusses the current role of preimplantation genetic testing in the management of recurrent pregnancy

  6. Frontotemporal lobar degeneration: current perspectives

    Directory of Open Access Journals (Sweden)

    Riedl L

    2014-02-01

    inhibitors to reduce behavioral disturbances. No large-scale or high-quality studies have been conducted to determine the efficacy of non-pharmacological treatment approaches in FTLD. In view of the limited treatment options, caregiver education and support is currently the most important component of the clinical management. Keywords: review, frontotemporal dementia, frontotemporal lobar degeneration

  7. Placental exosomes in normal and complicated pregnancy.

    Science.gov (United States)

    Mitchell, Murray D; Peiris, Hassendrini N; Kobayashi, Miharu; Koh, Yong Q; Duncombe, Gregory; Illanes, Sebastian E; Rice, Gregory E; Salomon, Carlos

    2015-10-01

    While there is considerable contemporary interest in elucidating the role of placenta-derived extracellular vesicles in normal and complicated pregnancies and their utility as biomarkers and therapeutic interventions, progress in the field is hindered by a lack of standardized extracellular vesicle taxonomy and isolation protocols. The term "extracellular vesicle" is nonspecific and refers to all membrane-bound vesicles from nanometer to micrometer diameters and of different biogenic origins. To meaningfully ascribe biological function and/or diagnostic and therapeutic utility to extracellular vesicles, and in particular exosomes, greater specificity and vesicle characterization is required. The current literature relating to exosome biology must be interpreted in this context. Exosomes are a subtype of extracellular vesicle that are specifically defined by an endosomal biogenesis and particle size (40-120 nm) and density (1.13-1.19 g/mL(-1)). Exosomes are specifically package with signaling molecules (including protein, messenger RNA, microRNA, and noncoding RNA) and are released by exocytosis into biofluid compartments. Exosomes regulate the activity of both proximal and distal target cells, including translational activity, angiogenesis, proliferation, metabolism, and apoptosis. As such, exosomal signaling represents an integral pathway mediating intercellular communication. During pregnancy, the placenta releases exosomes into the maternal circulation from as early as 6 weeks of gestation. Release is regulated by factors that include both oxygen tension and glucose concentration and correlates with placental mass and perfusion. The concentration of placenta-derived exosomes in maternal plasma increases progressively during gestation. Exosomes isolated from maternal plasma are bioactive in vitro and are incorporated into target cells by endocytosis. While the functional significance of placental exosomes in pregnancy remains to be fully elucidated, available

  8. Exosomes and Cardiovascular Protection.

    Science.gov (United States)

    Davidson, Sean M; Takov, Kaloyan; Yellon, Derek M

    2017-02-01

    Most, if not all, cells of the cardiovascular system secrete small, lipid bilayer vesicles called exosomes. Despite technical challenges in their purification and analysis, exosomes from various sources have been shown to be powerfully cardioprotective. Indeed, it is possible that much of the so-called "paracrine" benefit in cardiovascular function obtained by stem cell therapy can be replicated by the injection of exosomes produced by stem cells. However, exosomes purified from plasma appear to be just as capable of activating cardioprotective pathways. We discuss the potential roles of endogenous exosomes in the cardiovascular system, how this is perturbed in cardiovascular disease, and evaluate their potential as therapeutic agents to protect the heart.

  9. Exosomes: Mechanisms of Uptake

    Directory of Open Access Journals (Sweden)

    Kelly J. McKelvey

    2015-07-01

    Full Text Available Exosomes are 30–100 nm microvesicles which contain complex cellular signals of RNA, protein and lipids. Because of this, exosomes are implicated as having limitless therapeutic potential for the treatment of cancer, pregnancy complications, infections, and autoimmune diseases. To date we know a considerable amount about exosome biogenesis and secretion, but there is a paucity of data regarding the uptake of exosomes by immune and non-immune cell types (e.g., cancer cells and the internal signalling pathways by which these exosomes elicit a cellular response. Answering these questions is of paramount importance.

  10. Exosomes: Mechanisms of Uptake

    Directory of Open Access Journals (Sweden)

    Kelly J. McKelvey

    2015-07-01

    Full Text Available Exosomes are 30–100 nm microvesicles which contain complex cellular signals of RNA, protein and lipids. Because of this, exosomes are implicated as having limitless therapeutic potential for the treatment of cancer, pregnancy complications, infections, and autoimmune diseases. To date we know a considerable amount about exosome biogenesis and secretion, but there is a paucity of data regarding the uptake of exosomes by immune and non- immune cell types (e.g., cancer cells and the internal signalling pathways by which these exosomes elicit a cellular response. Answering these questions is of para‐ mount importance.

  11. Exosomes: the ideal nanovectors for biodelivery.

    Science.gov (United States)

    Fais, Stefano; Logozzi, Mariantonia; Lugini, Luana; Federici, Cristina; Azzarito, Tommaso; Zarovni, Natasa; Chiesi, Antonio

    2013-01-01

    Nanomedicine aims to exploit the improved and often novel physical, chemical, and biological properties of materials at the nanometric scale, possibly with the highest level of biomimetism, an approach that simulates what occurs in nature. Although extracellularly released vesicles include both microvesicles (MVs) and exosomes, only exosomes have the size that may be considered suitable for potential use in nanomedicine. In fact, recent reports have shown that exosomes are able to interact with target cells within an organ or at a distance using different mechanisms. Much is yet to be understood about exosomes, and currently, we are looking at the visible top of an iceberg, with most of what we have to understand on these nanovesicles still under the sea. In fact, we know that exosomes released by normal cells always trigger positive effects, whereas those released by cells in pathological condition, such as tumor or infected cells, may induce undesired, dangerous, and mostly unknown effects, but we cannot exclude the possibility that exosomes may also be detrimental for the body in normal conditions. However, whether we consider extracellular vesicles as a whole, thus including MVs, it appears that even in normal conditions, extracellular vesicles may lead to unwanted effects, depending on gender and age. This review aims to critically emphasize existing data in the literature that support the possible roles of exosomes in both diagnostic and therapeutic scopes.

  12. Functional Roles and Therapeutic Applications of Exosomes in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Laura Santangelo

    2017-01-01

    Full Text Available Exosomes are important in intercellular communication. They assure the horizontal transfer of specific functional contents (i.e., proteins, lipids, RNA molecules, and circulating DNA from donor to recipient cells. Notably, tumor-derived exosomes (TDEs appear to be an important vehicle of specific signals in cancer, impacting on tumor growth and metastasis. Recent researches point to the characterization of exosomes in Hepatocellular Carcinoma (HCC, the major adult liver malignancy. In this review, we summarize current findings on HCC exosomes, focusing on the identification of noncoding RNAs as exosome-enriched functional regulators and new potential biomarkers. The great potential of exosomes in future HCC diagnostic and therapeutic approaches is underlined.

  13. Hypoplastic left heart syndrome: current perspectives

    OpenAIRE

    Greenleaf, Christopher E.; Urencio, J. Miguel; Salazar, Jorge D.; Dodge-Khatami, Ali

    2016-01-01

    Since the first successful intervention for hypoplastic left heart syndrome (HLHS) was undertaken by Norwood in 1983, there have been many advancements in the pre-, intra-, and postoperative care of these children for a diagnosis that just 25 years ago was almost certainly a fatal one. This paper aims to describe the most recent trends and perspectives on the treatment of HLHS. In particular, we will discuss the five current options for HLHS, including Norwood stage I as the beginning to 3-st...

  14. Exosomes in the Pathology of Neurodegenerative Diseases.

    Science.gov (United States)

    Howitt, Jason; Hill, Andrew F

    2016-12-23

    More than 30 years ago, two unexpected findings were discovered that challenged conventional thinking in biology. The first was the identification of a misfolded protein with transmissible properties associated with a group of neurodegenerative diseases known as transmissible spongiform encephalopathies. The second was the discovery of a new pathway used for the extracellular release of biomolecules, including extracellular vesicles called exosomes. Two decades later, the convergence of these pathways was shown when exosomes were found to play a significant role in both the transmission and propagation of protein aggregates in disease. Recent research has now revealed that the majority of proteins involved in neurodegenerative diseases are transported in exosomes, and that external stresses due to age-related impairment of protein quality control mechanisms can promote the transcellular flux of these proteins in exosomes. Significantly, exosomes provide an environment that can induce the conformational conversion of native proteins into aggregates that can be transmitted to otherwise aggregate-free cells in the brain. Here we review the current roles of exosomes in the pathology of neurodegenerative diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Hypoplastic left heart syndrome: current perspectives

    Science.gov (United States)

    Greenleaf, Christopher E.; Urencio, J. Miguel; Salazar, Jorge D.

    2016-01-01

    Since the first successful intervention for hypoplastic left heart syndrome (HLHS) was undertaken by Norwood in 1983, there have been many advancements in the pre-, intra-, and postoperative care of these children for a diagnosis that just 25 years ago was almost certainly a fatal one. This paper aims to describe the most recent trends and perspectives on the treatment of HLHS. In particular, we will discuss the five current options for HLHS, including Norwood stage I as the beginning to 3-stage palliation, transplant, true hybrid, hybrid-bridge-to-Norwood, and compassionate care. PMID:27709095

  16. Exosomes participate in the carcinogenesis and the malignant behavior of gastric cancer.

    Science.gov (United States)

    Yan, Yunmeng; Fu, Guangzhen; Ye, Yafei; Ming, Liang

    2017-05-01

    In order to summarize the role of exosomes in invasion and metastasis in gastric cancer (GC). Exosomes are vesicles of endocytic origin ranging from 30 to 100 nm in size; they are composed of a lipid bilayer and contain DNA, mRNA, miRNA, circular RNA and multiple proteins. Recently, increasing evidence shows that exosomes play a crucial role in the tumorigenesis of GC. In this review, we focus on the latest findings on GC exosomes, mainly summarizing their role in invasion and metastasis in GC. Then, exosomes? potential functions as novel diagnostic and therapeutic biomarkers for GC are briefly discussed. At last, we prospect the clinical application perspective of exosomes in GC. Exosomes play a vital role in gastric cancer carcinogenesis and metastasis.

  17. Circulating osteocyte-derived exosomes contain miRNAs which are enriched in exosomes from MLO-Y4 cells.

    Science.gov (United States)

    Sato, Mari; Suzuki, Tomohide; Kawano, Mitsuoki; Tamura, Masato

    2017-02-01

    Signaling molecules produced by osteocytes have been proposed to serve as soluble factors that contribute to bone remodeling, as well as to homeostasis of other organs. However, to the best of our knowledge, there are currently no studies investigating the role of osteocyte-secreted exosomes. In the present study, ablation of osteocytes in mice [osteocyte-less (OL)] was used to examine the microRNA (miRNA) levels of plasma-circulating exosomes. In order to investigate the function of osteocyte-secreted exosomes, exosomes derived from MLO-Y4 cells were extracted and their miRNA expression levels were examined using miRNA array analysis and deep sequencing. Comparison of miRNA expression levels between plasma exosomes from OL mouse plasma and MLO-Y4-derived exosomes revealed that decreases in the number of miRNAs from exosomes circulating in the OL mouse plasma may be caused by a decrease in secretion of exosomes from osteocytes. These results suggest that osteocytes secrete exosomes containing characterized miRNAs and then circulate in the blood, and may thus transfer their components, including miRNAs, to recipient cells where they function as signaling molecules in other organs and/or tissues to regulate biological responses.

  18. Therapeutic Uses of Exosomes

    Directory of Open Access Journals (Sweden)

    Zacharias E. Suntres

    2013-01-01

    Full Text Available Exosomes are membrane vesicles with a diameter of 40–100 nm that are secreted by many cell types into the extracellular milieu. Exosomes are found in cell culture supernatants and in different biological fluids and are known to be secreted by most cell types under normal and pathological conditions. Considerable research is focusing on the exploitation of exosomes in biological fluids for biomarkers in the diagnosis of disease. More recently, exosomes are being exploited for their therapeutic potential. Exosomes derived from dendritic cells, tumor cells, and malignant effusions demonstrate immunomodulatory functions and are able to present antigens to T-cells and stimulate antigen-specific T-cell responses. Exosomes have also been examined for their therapeutic potential in the treatment of infections such as toxoplasmosis, diphtheria, tuberculosis and atypical severe acute respiratory syndrome as well as autoimmune diseases. Attempts to find practical applications for exosomes continue to expand with the role of exosomes as a drug delivery system for the treatment of autoimmune/inflammatory diseases and cancers.

  19. Primordial Germ Cells: Current Knowledge and Perspectives

    Directory of Open Access Journals (Sweden)

    Aleksandar Nikolic

    2016-01-01

    Full Text Available Infertility is a condition that occurs very frequently and understanding what defines normal fertility is crucial to helping patients. Causes of infertility are numerous and the treatment often does not lead to desired pregnancy especially when there is a lack of functional gametes. In humans, the primordial germ cell (PGC is the primary undifferentiated stem cell type that will differentiate towards gametes: spermatozoa or oocytes. With the development of stem cell biology and differentiation protocols, PGC can be obtained from pluripotent stem cells providing a new therapeutic possibility to treat infertile couples. Recent studies demonstrated that viable mouse pups could be obtained from in vitro differentiated stem cells suggesting that translation of these results to human is closer. Therefore, the aim of this review is to summarize current knowledge about PGC indicating the perspective of their use in both research and medical application for the treatment of infertility.

  20. Neurobiology of Consciousness: Current Research and Perspectives

    Directory of Open Access Journals (Sweden)

    Płonka Beata

    2015-12-01

    Full Text Available Scientific, objective approach to consciousness has allowed to obtain some experimental data concerning brain activity, ignoring, however, the longstanding philosophical tradition. Spectacular development of neuroscience which has been observed recently made this dissonance particularly noticeable. The paper addresses the main problems of discrepancy between neurobiological research and philosophical perspective. Current opinions concerning neural correlates and models of consciousness are discussed, as well as the problems of working memory, attention, self, and disorders of consciousness. A new neurobiological approach to describe brain function in terms of brain connectivity (so-called connectome is also presented. Finally, the need to introduce at least some aspects of philosophical approach directly into neurobiological research of consciousness is postulated.

  1. Maggot debridement therapy: the current perspectives

    Directory of Open Access Journals (Sweden)

    Naik G

    2017-10-01

    Full Text Available Gurudutt Naik, Keith G Harding Welsh Wound Innovation Centre, Cardiff University, Cardiff, UK Abstract: Chronic wounds remain a challenge to most healthcare systems worldwide despite the technological advances we have seen to date. Many chronic non-healing wounds require alternative approaches, in addition to standard conventional therapies. Maggot debridement therapy (MDT or the use of maggots to treat wounds is one such therapy that has been in use for centuries. We conducted a review of articles published in PubMed, NICE evidence documents, and linked literature with the aim of providing a brief perspective on the evolution of MDT, and the context in which maggot therapy is currently used along with evidence behind such methods. Keywords: wound healing, maggot debridement therapy, debridement, Lucilia sericata, chronic disease, larva

  2. Optimal management of genital herpes: current perspectives.

    Science.gov (United States)

    Sauerbrei, Andreas

    2016-01-01

    As one of the most common sexually transmitted diseases, genital herpes is a global medical problem with significant physical and psychological morbidity. Genital herpes is caused by herpes simplex virus type 1 or type 2 and can manifest as primary and/or recurrent infection. This manuscript provides an overview about the fundamental knowledge on the virus, its epidemiology, and infection. Furthermore, the current possibilities of antiviral therapeutic interventions and laboratory diagnosis of genital herpes as well as the present situation and perspectives for the treatment by novel antivirals and prevention of disease by vaccination are presented. Since the medical management of patients with genital herpes simplex virus infection is often unsatisfactory, this review aims at all physicians and health professionals who are involved in the care of patients with genital herpes. The information provided would help to improve the counseling of affected patients and to optimize the diagnosis, treatment, and prevention of this particular disease.

  3. Diabetes & coronary heart disease: current perspectives.

    Science.gov (United States)

    Ali, Mohammed K; Narayan, K M Venkat; Tandon, Nikhil

    2010-11-01

    Coronary heart disease (CHD) is currently the leading cause of death worldwide and together with diabetes, poses a serious health threat, particularly in the Indian Asian population. Risk factor management has evolved considerably with the continued emergence of new and thought-provoking evidence. The stream of laboratory- and population-based research findings as well as unresolved controversies may pose dilemmas and conflicting impulses in most clinicians, and even in our more well-informed patients. As results of the most recent clinical trials on glycaemic control for macrovascular risk reduction are woven into concrete clinical practice guidelines, this paper seeks to sort through unwieldy evidence, keeping these findings in perspective, to deliver a clearer message for the context of South Asia and cardio-metabolic risk management.

  4. The roles and implications of exosomes in sarcoma

    Science.gov (United States)

    Min, Li; Shen, Jacson; Tu, Chongqi; Hornicek, Francis; Duan, Zhenfeng

    2016-01-01

    Better diagnostic biomarkers and therapeutic options are still necessary for patients with sarcomas due to the current limitations of diagnosis and treatment. Exosomes are small extracellular membrane vesicles that are released by various cells and are found in most body fluids. Tumor-derived exosomes have been proven to mediate tumorigenesis, intercellular communication, microenvironment modulation, and metastasis in different cancers, including in sarcomas. Recently, exosomes have been considered as potential biomarkers for sarcoma diagnosis, prognosis, and possible targets for sarcoma therapy. Moreover, due to their specific cell-tropism and bioavailability, exosomes can also be engineered as vehicles for drug delivery. In this review, we discuss recent advances in the roles of tumor-derived exosomes in sarcoma and their potential clinical applications. PMID:27342745

  5. Exergaming and obesity in youth: current perspectives

    Directory of Open Access Journals (Sweden)

    Zeng N

    2016-08-01

    Full Text Available Nan Zeng, Zan Gao College of Education and Human Development, School of Kinesiology, University of Minnesota, Minneapolis, MN, USA Abstract: Although exergaming has been used as a physical activity modality among various populations, the evidence regarding its effectiveness on health-related outcomes in overweight/obese individuals remains unclear. The current study systematically reviewed literature and summarized findings of exergame-based interventions in overweight/obese populations with the goal of clarifying the current perspectives on exergaming and obesity. The initial search yielded 202 articles from six databases; 12 studies were included after evaluating for inclusion criteria and removing duplicates. Among these studies, seven were randomized controlled trials, two were control trials, and three were comparison studies. Overall, exergaming has the potential to attenuate weight gain and shows promise when used for physical activity and physical fitness promotion. Further, exergame play is positively associated with psychological well-being, but its effects on physiological outcomes are inconclusive. Finally, effects of exergaming on energy intake are not clear. Existing evidence supports that exergaming may elicit some health benefits in people who are overweight or/and obese. The limited number of available randomized controlled trials, however, restrict the ability to draw a conclusion that exergaming can trigger a change in all health-related outcomes. More research is warranted to make definitive conclusions regarding the effects of exergaming on health-related outcomes in such populations. Keywords: active video game, weight loss, children and adolescents, systematic review

  6. Exercise after breast cancer treatment: current perspectives

    Directory of Open Access Journals (Sweden)

    Dieli-Conwright CM

    2015-10-01

    Full Text Available Christina M Dieli-Conwright, Breanna Z Orozco Division of Biokinesiology and Physical Therapy, Women's Health and Exercise Laboratory, University of Southern California, Los Angeles, CA, USA Abstract: Over the past 2 decades, great strides have been made in the field of exercise-oncology research, particularly with breast cancer. This area of research is particularly important since there are >2.8 million breast cancer survivors who are in need of an intervention that can offset treatment-related side effects. Noticeable reductions in physical fitness (ie, cardiopulmonary fitness and muscular strength, negative changes in body composition (ie, increase in body mass, decrease in lean body mass, and increase in fat mass, increased fatigue, depression, or anxiety are some of the common side effects of cancer treatments that negatively impact overall quality of life and increase the risk for the development of comorbidities. Exercise plays a vital role in improving cardiopulmonary function, psychological events, muscular strength, and endurance in breast cancer survivors, and thus should be considered as a key factor of lifestyle intervention to reverse negative treatment-related side effects. The purpose of this review is to address current perspectives on the benefits of aerobic and resistance exercise after breast cancer treatments. This review is focused on the well-established benefits of exercise on physical and emotional well-being, bone health, lymphedema management, and the postulated benefits of exercise on risk reduction for recurrence of breast cancer. Keywords: breast cancer, exercise, physical well-being

  7. Biogas production: current state and perspectives.

    Science.gov (United States)

    Weiland, Peter

    2010-01-01

    Anaerobic digestion of energy crops, residues, and wastes is of increasing interest in order to reduce the greenhouse gas emissions and to facilitate a sustainable development of energy supply. Production of biogas provides a versatile carrier of renewable energy, as methane can be used for replacement of fossil fuels in both heat and power generation and as a vehicle fuel. For biogas production, various process types are applied which can be classified in wet and dry fermentation systems. Most often applied are wet digester systems using vertical stirred tank digester with different stirrer types dependent on the origin of the feedstock. Biogas is mainly utilized in engine-based combined heat and power plants, whereas microgas turbines and fuel cells are expensive alternatives which need further development work for reducing the costs and increasing their reliability. Gas upgrading and utilization as renewable vehicle fuel or injection into the natural gas grid is of increasing interest because the gas can be used in a more efficient way. The digestate from anaerobic fermentation is a valuable fertilizer due to the increased availability of nitrogen and the better short-term fertilization effect. Anaerobic treatment minimizes the survival of pathogens which is important for using the digested residue as fertilizer. This paper reviews the current state and perspectives of biogas production, including the biochemical parameters and feedstocks which influence the efficiency and reliability of the microbial conversion and gas yield.

  8. NK cell-released exosomes

    OpenAIRE

    Fais, Stefano

    2013-01-01

    We have recently reported that human natural killer (NK) cells release exosomes that express both NK-cell markers and cytotoxic molecules. Similar results were obtained with circulating exosomes from human healthy donors. Both NK-cell derived and circulating exosomes exerted a full functional activity and killed both tumor and activated immune cells. These findings indicate that NK-cell derived exosomes might constitute a new promising therapeutic tool.

  9. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Lijuan [Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Wang, Yingjie [Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Internal Medicine of Traditional Chinese Medicine, Shuguang Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Pan, Yaohua; Zhang, Lan [Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Shen, Chengxing [Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University, Shanghai (China); Qin, Gangjian [Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 (United States); Ashraf, Muhammad [Pathology and Lab Med, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Weintraub, Neal [Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Ma, Genshan, E-mail: magenshan@hotmail.com [Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Tang, Yaoliang, E-mail: tangyg@ucmail.uc.edu [Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States)

    2013-02-15

    Highlights: ► Cardiac progenitor-derived (CPC) Exosomes protect H9C2 from apoptosis in vitro. ► CPC-exosomes protect cardiomyoyctes from MI/R induced apoptosis in vivo. ► CPC-exosomes were taken up by H9C2 with high efficiency using PKH26 labeling. ► miR-451, one of GATA4-responsive miRNA cluster, is enriched in CPC-exosomes. -- Abstract: Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation invitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (p < 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.

  10. Managing hyperthyroidism in pregnancy: current perspectives

    Science.gov (United States)

    Andersen, Stine Linding; Laurberg, Peter

    2016-01-01

    Hyperthyroidism in women who are of childbearing age is predominantly of autoimmune origin and caused by Graves’ disease. The physiological changes in the maternal immune system during a pregnancy may influence the development of this and other autoimmune diseases. Furthermore, pregnancy-associated physiological changes influence the synthesis and metabolism of thyroid hormones and challenge the interpretation of thyroid function tests in pregnancy. Thyroid hormones are crucial regulators of early development and play an important role in the maintenance of a normal pregnancy and in the development of the fetus, particularly the fetal brain. Untreated or inadequately treated hyperthyroidism is associated with pregnancy complications and may even program the fetus to long-term development of disease. Thus, hyperthyroidism in pregnant women should be carefully managed and controlled, and proper management involves different medical specialties. The treatment of choice in pregnancy is antithyroid drugs (ATDs). These drugs are effective in the control of maternal hyperthyroidism, but they all cross the placenta, and so need careful management and control during the second half of pregnancy considering the risk of fetal hyper- or hypothyroidism. An important aspect in the early pregnancy is that the predominant side effect to the use of ATDs in weeks 6–10 of pregnancy is birth defects that may develop after exposure to available types of ATDs and may be severe. This review focuses on four current perspectives in the management of overt hyperthyroidism in pregnancy, including the etiology and incidence of the disease, how the diagnosis is made, the consequences of untreated or inadequately treated disease, and finally how to treat overt hyperthyroidism in pregnancy. PMID:27698567

  11. Semiconductor plasmonic nanolasers: current status and perspectives.

    Science.gov (United States)

    Gwo, Shangjr; Shih, Chih-Kang

    2016-08-01

    Scaling down semiconductor lasers in all three dimensions holds the key to the development of compact, low-threshold, and ultrafast coherent light sources, as well as integrated optoelectronic and plasmonic circuits. However, the minimum size of conventional semiconductor lasers utilizing dielectric cavity resonators (photonic cavities) is limited by the diffraction limit. To date, surface plasmon amplification by stimulated emission of radiation (spaser)-based plasmonic nanolaser is the only photon and plasmon-emitting device capable of this remarkable feat. Specifically, it has been experimentally demonstrated that the use of plasmonic cavities based on metal-insulator-semiconductor (MIS) nanostructures can indeed break the diffraction limit in all three dimensions. In this review, we present an updated overview of the current status for plasmonic nanolasers using the MIS configuration and other related metal-cladded semiconductor microlasers. In particular, by using composition-varied indium gallium nitride/gallium nitride core-shell nanorods, it is possible to realize all-color, single-mode nanolasers in the full visible wavelength range with ultralow continuous-wave (CW) lasing thresholds. The lasing action in these subdiffraction plasmonic cavities is achieved via a unique auto-tuning mechanism based on the property of weak size dependence inherent in plasmonic nanolasers. As for the choice of metals in the plasmonic structures, epitaxial silver films and giant colloidal silver crystals have been shown to be the superior constituent materials for plasmonic cavities due to their low plasmonic losses in the visible and near-infrared (NIR) spectral regions. In this review, we also provide some perspectives on the challenges and opportunities in this exciting new research frontier.

  12. Managing hyperthyroidism in pregnancy: current perspectives

    Directory of Open Access Journals (Sweden)

    Andersen SL

    2016-09-01

    Full Text Available Stine Linding Andersen,1,2 Peter Laurberg1,3,† 1Department of Endocrinology, Aalborg University Hospital, 2Department of Clinical Biochemistry, Aalborg University Hospital, 3Department of Clinical Medicine, Aalborg University, Aalborg, Denmark †Peter Laurberg passed away on June 20, 2016 Abstract: Hyperthyroidism in women who are of childbearing age is predominantly of autoimmune origin and caused by Graves’ disease. The physiological changes in the maternal immune system during a pregnancy may influence the development of this and other autoimmune diseases. Furthermore, pregnancy-associated physiological changes influence the synthesis and metabolism of thyroid hormones and challenge the interpretation of thyroid function tests in pregnancy. Thyroid hormones are crucial regulators of early development and play an important role in the maintenance of a normal pregnancy and in the development of the fetus, particularly the fetal brain. Untreated or inadequately treated hyperthyroidism is associated with pregnancy complications and may even program the fetus to long-term development of disease. Thus, hyperthyroidism in pregnant women should be carefully managed and controlled, and proper management involves different medical specialties. The treatment of choice in pregnancy is antithyroid drugs (ATDs. These drugs are effective in the control of maternal hyperthyroidism, but they all cross the placenta, and so need careful management and control during the second half of pregnancy considering the risk of fetal hyper- or hypothyroidism. An important aspect in the early pregnancy is that the predominant side effect to the use of ATDs in weeks 6–10 of pregnancy is birth defects that may develop after exposure to available types of ATDs and may be severe. This review focuses on four current perspectives in the management of overt hyperthyroidism in pregnancy, including the etiology and incidence of the disease, how the diagnosis is made, the

  13. Managing hyperthyroidism in pregnancy: current perspectives.

    Science.gov (United States)

    Andersen, Stine Linding; Laurberg, Peter

    2016-01-01

    Hyperthyroidism in women who are of childbearing age is predominantly of autoimmune origin and caused by Graves' disease. The physiological changes in the maternal immune system during a pregnancy may influence the development of this and other autoimmune diseases. Furthermore, pregnancy-associated physiological changes influence the synthesis and metabolism of thyroid hormones and challenge the interpretation of thyroid function tests in pregnancy. Thyroid hormones are crucial regulators of early development and play an important role in the maintenance of a normal pregnancy and in the development of the fetus, particularly the fetal brain. Untreated or inadequately treated hyperthyroidism is associated with pregnancy complications and may even program the fetus to long-term development of disease. Thus, hyperthyroidism in pregnant women should be carefully managed and controlled, and proper management involves different medical specialties. The treatment of choice in pregnancy is antithyroid drugs (ATDs). These drugs are effective in the control of maternal hyperthyroidism, but they all cross the placenta, and so need careful management and control during the second half of pregnancy considering the risk of fetal hyper- or hypothyroidism. An important aspect in the early pregnancy is that the predominant side effect to the use of ATDs in weeks 6-10 of pregnancy is birth defects that may develop after exposure to available types of ATDs and may be severe. This review focuses on four current perspectives in the management of overt hyperthyroidism in pregnancy, including the etiology and incidence of the disease, how the diagnosis is made, the consequences of untreated or inadequately treated disease, and finally how to treat overt hyperthyroidism in pregnancy.

  14. Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery.

    Directory of Open Access Journals (Sweden)

    Costanza Emanueli

    Full Text Available Exosome nanoparticles carry a composite cargo, including microRNAs (miRs. Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG surgery, we investigated if: 1 exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2 circulating exosomes and exosomal cardiac miRs correlate with cardiac troponin (cTn, the current "gold standard" surrogate biomarker of myocardial damage.The concentration of exosome-sized nanoparticles was determined in serial plasma samples. Cardiac-expressed (miR-1, miR-24, miR-133a/b, miR-208a/b, miR-210, non-cardiovascular (miR-122 and quality control miRs were measured in whole plasma and in plasma exosomes. Linear regression analyses were employed to establish the extent to which the circulating individual miRs, exosomes and exosomal cardiac miR correlated with cTn-I. Cardiac-expressed miRs and the nanoparticle number increased in the plasma on completion of surgery for up to 48 hours. The exosomal concentration of cardiac miRs also increased after CABG. Cardiac miRs in the whole plasma did not correlate significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs.The plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers in cardiac patients.

  15. Exosomes: Nanoparticulate tools for RNA interference and drug delivery.

    Science.gov (United States)

    Shahabipour, Fahimeh; Barati, Nastaran; Johnston, Thomas P; Derosa, Giuseppe; Maffioli, Pamela; Sahebkar, Amirhossein

    2017-07-01

    Exosomes are naturally occurring extracellular vesicles released by most mammalian cells in all body fluids. Exosomes are known as key mediators in cell-cell communication and facilitate the transfer of genetic and biochemical information between distant cells. Structurally, exosomes are composed of lipids, proteins, and also several types of RNAs which enable these vesicles to serve as important disease biomarkers. Moreover, exosomes have emerged as novel drug and gene delivery tools owing to their multiple advantages over conventional delivery systems. Recently, increasing attention has been focused on exosomes for the delivery of drugs, including therapeutic recombinant proteins, to various target tissues. Exosomes are also promising vehicles for the delivery of microRNAs and small interfering RNAs, which is usually hampered by rapid degradation of these RNAs, as well as inefficient tissue specificity of currently available delivery strategies. This review highlights the most recent accomplishments and trends in the use of exosomes for the delivery of drugs and therapeutic RNA molecules. © 2017 Wiley Periodicals, Inc.

  16. Exosomes as a liquid biopsy for lung cancer.

    Science.gov (United States)

    Cui, Shaohua; Cheng, Zhuoan; Qin, Wenxin; Jiang, Liyan

    2018-02-01

    In lung cancer and other malignancies, the so-called "liquid biopsy" is quickly moving into clinical practice. Its full potential has not yet been fully identified, but the "liquid biopsy" is no longer a promise but has become a reality that allows for better treatment selection and monitoring of lung cancer. This emerging field has significant potential to make up for the limitations of the traditional tissue-derived biomaterials. Exosomes are spherical nano-sized vesicles with a diameter of 40-100 nm and a density of 1.13-1.19 g/ml. In both physiological and pathological conditions, exosomes can be released by different cell types, including immune cells, stem cells and tumor cells. These small molecules may serve as promising biomarkers in lung cancer "liquid biopsy" as they can be easily obtained from most body fluids. In addition, the lipid bilayer of exosomes allows for stable cargoes which are relatively hard to degrade. Furthermore, the composition of exosomes reflects that of their parental cells, suggesting that exosomes are potential surrogates of the original cells and, therefore, are useful for understanding cell biology. Previous studies have demonstrated that exosomes play important roles in cell-to-cell communication. Moreover, tumor-derived exosomes are evolved in tumor-specific biological process, including tumor proliferation and progression. Recently, a growing number of studies has focused on exosomal cargo and their use in lung cancer genesis and progression. In addition, their utility as lung cancer diagnostic, prognostic and predictive biomarkers have also been studied. The current review primarily summaries lung cancer-related exosomal biomarkers that have recently been identified and discusses their potential in clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Exosomes from Osteosarcoma and normal osteoblast differ in proteomic cargo and immunomodulatory effects on T cells.

    Science.gov (United States)

    Troyer, Ryan M; Ruby, Carl E; Goodall, Cheri P; Yang, Liping; Maier, Claudia S; Albarqi, Hassan A; Brady, Jacqueline V; Bathke, Kallan; Taratula, Oleh; Mourich, Dan; Bracha, Shay

    2017-09-15

    Canine osteosarcoma (OSA) is the most common cancer of the appendicular skeleton and is associated with high metastatic rate to the lungs and poor prognosis. Recent studies have shown the impact of malignant-derived exosomes on immune cells and the facilitation of immune evasion. In the current study, we have characterized the proteomic profile of exosomes derived from healthy osteoblasts and osteosarcoma cell lines. We investigated the direct impact of these exosomes on healthy T cells. Proteomic cargo of the malignant exosomes was markedly different from osteoblastic exosomes and contained immunosuppressive proteins including TGF-β, α fetoprotein and heat shock proteins. OSA exosomes directly attenuated the rate of T cell proliferation, increased a regulatory (FoxP3+) CD4+ phenotype and diminished the expression of the activation marker CD25+ on CD8+ cells. Exosomes of osteoblasts also demonstrated a direct impact on T cells, but to a lesser degree. Osteosarcoma-derived exosomes compared to normal osteoblasts contain an immunomodulatory cargo, which reduced the rate of T cell proliferation and promoted T regulatory phenotype. Osteoblast-derived exosomes can also reduce T cell activity, but to lesser degree compared to OSA exosomes and without promoting a T regulatory phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Ethical Perspectives on the Current Controversy Regarding Openness in Adoption.

    Science.gov (United States)

    Tavis, Timothy M.

    This paper outlines current changes in American adoption practice and the controversies surrounding these changes. It includes a discussion of the role that neo-Kantian and utilitarian perspectives have played in American adoption policy and practice, and offers an alternative, the communitarian perspective, described by Sandel (1984). Adoption…

  19. Urinary Exosomes: The Potential for Biomarker Utility, Intercellular Signaling and Therapeutics in Urological Malignancy.

    Science.gov (United States)

    Franzen, Carrie A; Blackwell, Robert H; Foreman, Kimberly E; Kuo, Paul C; Flanigan, Robert C; Gupta, Gopal N

    2016-05-01

    Exosomes are small secreted vesicles that contain proteins, mRNA and miRNA with the potential to alter signaling pathways in recipient cells. While exosome research has flourished, few publications have specifically considered the role of genitourinary cancer shed exosomes in urine, their implication in disease progression and their usefulness as noninvasive biomarkers. In this review we examined the current literature on the role of exosomes in intercellular communication and as biomarkers, and their potential as delivery vehicles for therapeutic applications in bladder, prostate and renal cancer. We searched PubMed® and Google® with the key words prostate cancer, bladder cancer, kidney cancer, exosomes, microvesicles and urine. Relevant articles, including original research studies and reviews, were selected based on contents. A review of this literature was generated. Cancer exosomes can be isolated from urine using various techniques. Cancer cells have been found to secrete more exosomes than normal cells. These exosomes have a role in cellular communication by interacting with and depositing their cargo in target cells. Bladder, prostate and renal cancer exosomes have been shown to enhance migration, invasion and angiogenesis. These exosomes have also been shown to increase proliferation, confer drug resistance and promote immune evasion. Urinary exosomes can be isolated from bladder, kidney and prostate cancer. They serve as a potential reservoir for biomarker identification. Exosomes also have potential for therapeutics as siRNA or pharmacological agents can be loaded into exosomes. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  20. Augmented reality in dentistry: a current perspective.

    Science.gov (United States)

    Kwon, Ho-Beom; Park, Young-Seok; Han, Jung-Suk

    2018-02-21

    Augmentation reality technology offers virtual information in addition to that of the real environment and thus opens new possibilities in various fields. The medical applications of augmentation reality are generally concentrated on surgery types, including neurosurgery, laparoscopic surgery and plastic surgery. Augmentation reality technology is also widely used in medical education and training. In dentistry, oral and maxillofacial surgery is the primary area of use, where dental implant placement and orthognathic surgery are the most frequent applications. Recent technological advancements are enabling new applications of restorative dentistry, orthodontics and endodontics. This review briefly summarizes the history, definitions, features, and components of augmented reality technology and discusses its applications and future perspectives in dentistry.

  1. The biology, function and clinical implications of exosomes in lung cancer.

    Science.gov (United States)

    Zhou, Li; Lv, Tangfeng; Zhang, Qun; Zhu, Qingqing; Zhan, Ping; Zhu, Suhua; Zhang, Jianya; Song, Yong

    2017-10-28

    Exosomes are 30-100 nm small membrane vesicles of endocytic origin that are secreted by all types of cells, and can also be found in various body fluids. Increasing evidence implicates that exosomes confer stability and can deliver their cargos such as proteins and nucleic acids to specific cell types, which subsequently serve as important messengers and carriers in lung carcinogenesis. Here, we describe the biogenesis and components of exosomes mainly in lung cancer, we summarize their function in lung carcinogenesis (epithelial mesenchymal transition, oncogenic cell transformation, angiogenesis, metastasis and immune response in tumor microenvironment), and importantly we focus on the clinical potential of exosomes as biomarkers and therapeutics in lung cancer. In addition, we also discuss current challenges that might impede the clinical use of exosomes. Further studies on the functional roles of exosomes in lung cancer requires thorough research. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Characterization of human thymic exosomes

    OpenAIRE

    Gabriel Skogberg; Judith Gudmundsdottir; Sjoerd van der Post; Kerstin Sandström; Sören Bruhn; Mikael Benson; Lucia Mincheva-Nilsson; Vladimir Baranov; Esbjörn Telemo; Olov Ekwall

    2013-01-01

    Exosomes are nanosized membrane-bound vesicles that are released by various cell types and are capable of carrying proteins, lipids and RNAs which can be delivered to recipient cells. Exosomes play a role in intercellular communication and have been described to mediate immunologic information. In this article we report the first isolation and characterization of exosomes from human thymic tissue. Using electron microscopy, particle size determination, density gradient measurement, flow cytom...

  3. Targeting the nuclear RNA exosome

    DEFF Research Database (Denmark)

    Meola, Nicola; Jensen, Torben Heick

    2017-01-01

    Centrally positioned in nuclear RNA metabolism, the exosome deals with virtually all transcript types. This 3'-5' exo- and endo-nucleolytic degradation machine is guided to its RNA targets by adaptor proteins that enable substrate recognition. Recently, the discovery of the 'Poly(A) tail exosome...... targeting (PAXT)' connection as an exosome adaptor to human nuclear polyadenylated transcripts has relighted the interest of poly(A) binding proteins (PABPs) in both RNA productive and destructive processes....

  4. Chromoplast differentiation: current status and perspectives.

    Science.gov (United States)

    Egea, Isabel; Barsan, Cristina; Bian, Wanping; Purgatto, Eduardo; Latché, Alain; Chervin, Christian; Bouzayen, Mondher; Pech, Jean-Claude

    2010-10-01

    Chromoplasts are carotenoid-accumulating plastids conferring color to many flowers and fruits as well as to some tubers and roots. Chromoplast differentiation proceeds from preexisting plastids, most often chloroplasts. One of the most prominent changes is remodeling of the internal membrane system associated with the formation of carotenoid-accumulating structures. During the differentiation process the plastid genome is essentially stable and transcriptional activity is restricted. The buildup of the chromoplast for specific metabolic characteristics is essentially dependent upon the transcriptional activity of the nucleus. Important progress has been made in terms of mediation of the chloroplast-to-chromoplast transition with the discovery of the crucial role of the Or gene. In this article we review recent developments in the structural, biochemical and molecular aspects of chromoplast differentiation and also consider the reverse differentiation of chromoplasts into chloroplast-like structures during the regreening process occurring in some fruit. Future perspectives toward a full understanding of chromoplast differentiation include in-depth knowledge of the changes occurring in the plastidial proteome during chromoplastogenesis, elucidation of the role of hormones and the search for signals that govern the dialog between the nuclear and the chromoplastic genome.

  5. Ethnozoology in Brazil: current status and perspectives

    Directory of Open Access Journals (Sweden)

    Alves Rômulo RN

    2011-07-01

    Full Text Available Abstract Ancient connections between animals and human are seen in cultures throughout the world in multiple forms of interaction with the local fauna that form the core of Ethnozoology. Historically, ethnozoological publications grew out of studies undertaken in academic areas such as zoology, human ecology, sociology and anthropology - reflecting the interdisciplinary character of this discipline. The rich fauna and cultural diversity found in Brazil, with many different species of animals being used for an extremely wide diversity of purposes by Amerindian societies (as well as the descendents of the original European colonists and African slaves, presents an excellent backdrop for examining the relationships that exist between humans and other animals. This work presents a historical view of ethnozoological research in Brazil and examines its evolution, tendencies, and future perspectives. In summary, literature researches indicated that ethnozoology experienced significant advances in recent years in Brazil, although from a qualitative point of view improvement is still needed in terms of methodological procedures, taxonomic precision, and the use of quantitative techniques. A wide range of methodologies and theories are available in different areas of learning that can be put to good use in ethnozoological approaches if the right questions are asked. The challenges to studying ethnozoology in Brazil are not insignificant, and the tendencies described in the present study may aid in defining research strategies that will maintain the quantitative growth observed in the recent years but likewise foster needed qualitative improvements.

  6. Pathogenesis of ovarian cancer: current perspectives | Chesang ...

    African Journals Online (AJOL)

    Objective: To present a review of current knowledge of the pathogenesis of ovarian cancer and its clinical implications. Data Source: Extensive literature search was conducted to identify relevant studies. Study Selection: Studies in the English language about or related to pathogenesis of ovarian cancer were selected.

  7. Current perspectives on the evolution of birds

    NARCIS (Netherlands)

    Ericson, P.G.P.

    2008-01-01

    The paper summarizes the current understanding of the evolution and diversification of birds. New insights into this field have mainly come from two fundamentally different, but complementary sources of information: the many newly discovered Mesozoic bird fossils and the wealth of genetic analyses

  8. An innovative method for exosome quantification and size measurement.

    Science.gov (United States)

    Mehdiani, Arash; Maier, Anatol; Pinto, Antonio; Barth, Mareike; Akhyari, Payam; Lichtenberg, Artur

    2015-01-17

    Although the biological importance of exosomes has recently gained an increasing amount of scientific and clinical attention, much is still unknown about their complex pathways, their bioavailability and their diverse functions in health and disease. Current work focuses on the presence and the behavior of exosomes (in vitro as well as in vivo) in the context of different human disorders, especially in the fields of oncology, gynecology and cardiology. Unfortunately, neither a consensus regarding a gold standard for exosome isolation exists, nor is there an agreement on such a method for their quantitative analysis. As there are many methods for the purification of exosomes and also many possibilities for their quantitative and qualitative analysis, it is difficult to determine a combination of methods for the ideal approach. Here, we demonstrate nanoparticle tracking analysis (NTA), a semi-automated method for the characterization of exosomes after isolation from human plasma by ultracentrifugation. The presented results show that this approach for isolation, as well as the determination of the average number and size of exosomes, delivers reproducible and valid data, as confirmed by other methods, such as scanning electron microscopy (SEM).

  9. Exosomes are fingerprints of originating cells: potential biomarkers for ovarian cancer

    Directory of Open Access Journals (Sweden)

    Kobayashi M

    2015-03-01

    Full Text Available Miharu Kobayashi, Gregory E Rice, Jorge Tapia, Murray D Mitchell, Carlos Salomon Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. Abstract: The past decade has seen an extraordinary explosion of research in the field of extracellular vesicles, especially in a specific type of extracellular vesicles originating from endosomal compartments, called exosomes. Exosomes are a specific subtype of secreted vesicles that are defined as small (~30–120 nm but very stable membrane vesicles that are released from a wide range of cells, including normal and cancer cells. As the content of exosomes is cell type specific, it is believed that they are a "fingerprint" of the releasing cell and its metabolic status. We hypothesized that the exosomes and their specific exosomal content (eg, microribonucleic acid represent a precious biomedical tool and may be used as biomarkers for the diagnosis and prognosis of malignant tumors. In addition, exosomes may modify the phenotype of the parent and/or target cell by transferring pro-oncogenic molecules to induce cancerous phenotype of recipient cells and contribute to the formation of the premetastatic niche. The mechanism involved in these phenomena remains unclear; however, inclusion of signaling mediators into exosomes or exosome release may reduce their intracellular bioavailability in the parent cell, thereby altering cell phenotype and their metastatic potential. The aim of this review therefore is to analyze the biogenesis and role of exosomes from tumor cells, focusing primarily on ovarian cancer. Ovarian cancer is the most lethal gynecologic cancer, and an effective early diagnosis has the potential to improve patient survival. Ovarian cancer currently lacks a reliable method for early detection, however, exosomes have received great attention as potential biomarkers and mediators

  10. The RNA Exosome and RNA Exosome-linked Disease.

    Science.gov (United States)

    Morton, Derrick J; Kuiper, Emily G; Jones, Stephanie K; Leung, Sara W; Corbett, Anita H; Fasken, Milo B

    2017-11-01

    The RNA exosome is an evolutionarily conserved, ribonuclease complex that is critical for both processing and degradation of a variety of RNAs. Cofactors that associate with the RNA exosome likely dictate substrate specificity for this complex. Recently, mutations in genes encoding both structural subunits of the RNA exosome and its cofactors have been linked to human disease. Mutations in the RNA exosome genes EXOSC3 and EXOSC8 cause pontocerebellar hypoplasia type 1b (PCH1b) and type 1c (PCH1c), respectively, which are similar autosomal recessive, neurodegenerative diseases. Mutations in the RNA exosome gene EXOSC2 cause a distinct syndrome with various tissue-specific phenotypes including retinitis pigmentosa and mild intellectual disability. Mutations in genes that encode RNA exosome cofactors also cause tissue-specific diseases with complex phenotypes. How mutations in these genes give rise to distinct, tissue-specific diseases is not clear. In this review, we discuss the role of the RNA exosome complex and its cofactors in human disease, consider the amino acid changes that have been implicated in disease, and speculate on the mechanisms by which exosome gene mutations could underlie dysfunction and disease. Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  11. Current Issues in Teacher Education: History, Perspectives, and Implications

    Science.gov (United States)

    Lassonde, Cynthia A.; Michael, Robert J.; Rivera-Wilson, Jerusalem

    2008-01-01

    In this edited volume by experts in the field of teacher education, Current Issues in Teacher Education combines forces from the United States and Canada to present and discuss positions on current topics and concerns in the field of teacher education. It provides an overview and multiple perspectives of issues rather than one authority's position…

  12. Current perspective in agnogenic myeloid metaplasia.

    Science.gov (United States)

    Tefferi, A; Silverstein, M N

    1996-09-01

    Agnogenic myeloid metaplasia (AMM) carries the worst prognosis among the chronic myeloproliferative disorders. Substantial bone marrow fibrosis, extramedullary hematopoiesis, anemia and hepatosplenomegaly are the characteristic features of the disease. AMM is currently incurable and the available treatment agents are mostly palliative and do not prolong life. Two pathogenetic processes are responsible for the impaired hematopoiesis and the clinical manifestations. The primary disease process is a clonal hematopoietic stem cell disorder which results in chronic myeloproliferation and atypical megakaryocytic hyperplasia. The secondary process of bone marrow fibrosis is the result of non-clonal fibroblastic proliferation and hyperactivity induced by growth factors abnormally shed from clonal megakaryocytes. Therefore, experimental treatment strategies may be directed towards either one or both of these disease processes. This report summarizes the current management options and new therapeutic endeavours.

  13. Psychodiagnosis of the Adolescent: Current Perspectives

    OpenAIRE

    Oliveira, Frank de Souza; Centro Universitário de Maringá - UniCesumar; Morais, Izabel Cristina de; Centro Universitário de Maringá - UniCesumar; Greinert, Bruna Rafaele Milhorini; Centro Universitário de Maringá - UniCesumar; Milani, Rute Grossi; Centro Universitário de Maringá - UniCesumar

    2015-01-01

    Adolescence is culturally known as a critical phase in life, characterized by physical, social and emotional changes. These complex transformations, proper to human development, make possible the passage through a period of psychological instability. |Many adolescents require professional help during this phase. Current research characterizes the psychodiagnosis process with adolescents within the psychoanalytic paradigm. A survey was conducted on registers in electronic and library data base...

  14. Research in Humans: Current Perspectives in Brazil

    OpenAIRE

    Célia Alcantara Cunha Lima

    2016-01-01

    This work addressed the norms of ethics for human experimentation in Brazil, operationalized by the National Research Ethics Commission (CONEP) of the National Health Council (CNS). It analyzed international principles of bioethics as a theoretical framework for the Brazilian regulation. National and international publications were reviewed, by Capes periodicals, relating to historical ethical infractions, such as reflection to the current day. It analyzed the law (PL) 200/2015 of the Senate,...

  15. Research in Humans: Current Perspectives in Brazil

    Directory of Open Access Journals (Sweden)

    Célia Alcantara Cunha Lima

    2016-10-01

    Full Text Available This work addressed the norms of ethics for human experimentation in Brazil, operationalized by the National Research Ethics Commission (CONEP of the National Health Council (CNS. It analyzed international principles of bioethics as a theoretical framework for the Brazilian regulation. National and international publications were reviewed, by Capes periodicals, relating to historical ethical infractions, such as reflection to the current day. It analyzed the law (PL 200/2015 of the Senate, which proposes flexibilities in Brazilian legislation and concluded that the requested changes should be discussed in depth by bioethicists, scientists and Brazilian lawyers with extended discussion to society.

  16. Biomarkers in pancreatic adenocarcinoma: current perspectives

    Directory of Open Access Journals (Sweden)

    Swords DS

    2016-12-01

    Full Text Available Douglas S Swords, Matthew A Firpo, Courtney L Scaife, Sean J Mulvihill Department of Surgery, University of Utah Health Sciences, Salt Lake City, UT, USA Abstract: Pancreatic ductal adenocarcinoma (PDAC has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9, which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA, CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC. Keywords: pancreatic cancer, biomarkers, screening, CA 19-9, CEA

  17. Non Pharmacological Cognitive Enhancers - Current Perspectives.

    Science.gov (United States)

    Sachdeva, Ankur; Kumar, Kuldip; Anand, Kuljeet Singh

    2015-07-01

    Cognition refers to the mental processes involved in thinking, knowing, remembering, judging, and problem solving. Cognitive dysfunctions are an integral part of neuropsychiatric disorders as well as in healthy ageing. Cognitive Enhancers are molecules that help improve aspects of cognition like memory, intelligence, motivation, attention and concentration. Recently, Non Pharmacological Cognitive Enhancers have gained popularity as effective and safe alternative to various established drugs. Many of these Non Pharmacological Cognitive Enhancers seem to be more efficacious compared to currently available Pharmacological Cognitive Enhancers. This review describes and summarizes evidence on various Non Pharmacological Cognitive Enhancers such as physical exercise, sleep, meditation and yoga, spirituality, nutrients, computer training, brain stimulation, and music. We also discuss their role in ageing and different neuro-psychiatric disorders, and current status of Cochrane database recommendations. We searched the Pubmed database for the articles and reviews having the terms 'non pharmacological and cognitive' in the title, published from 2000 till 2014. A total of 11 results displayed, out of which 10 were relevant to the review. These were selected and reviewed. Appropriate cross-references within the articles along with Cochrane reviews were also considered and studied.

  18. Current pharmacotherapies for obesity: A practical perspective.

    Science.gov (United States)

    Golden, Angela

    2017-10-01

    To review the currently available pharmacotherapies for obesity management with a particular focus on the United States. Narrative review based on literature searches and the latest prescribing information (up to July 2017). Obesity pharmacotherapies may assist those individuals who have obesity, or overweight with comorbidities, who have failed to maintain weight loss with lifestyle modifications alone (caloric restriction and increased physical activity). Currently approved options in the United States include phentermine for short-term use and five obesity pharmacotherapies that can be used long-term (orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion, and liraglutide 3.0 mg). If the use of an obesity pharmacotherapy is indicated, treatment should be selected to provide the most appropriate option for each individual and their circumstances. Variables such as contraindications, individual comorbidities, patient choice, patient readiness to incorporate additional behavioral changes (e.g., alcohol prohibition), and cost should guide choices. Each of the obesity pharmacotherapies has advantages and disadvantages that can help guide treatment choice. Those receiving treatment may also have individual preferences based on factors such as administration route, frequency of dosing, and/or safety profile. In addition, some options may be particularly appropriate for patients with common obesity-related complications such as depression or diabetes. ©2017 American Association of Nurse Practitioners.

  19. Resolving sorting mechanisms into exosomes

    NARCIS (Netherlands)

    Stoorvogel, Willem

    2015-01-01

    The complexity of mechanisms driving protein sorting into exosomes is only beginning to emerge. In a paper recently published in Cell Research, Roucourt et al. report that trimming of heparan sulfate side chains of syndecans by endosomal heparanase facilitates sorting into exosomes by the formation

  20. Characterization of human thymic exosomes.

    Science.gov (United States)

    Skogberg, Gabriel; Gudmundsdottir, Judith; van der Post, Sjoerd; Sandström, Kerstin; Bruhn, Sören; Benson, Mikael; Mincheva-Nilsson, Lucia; Baranov, Vladimir; Telemo, Esbjörn; Ekwall, Olov

    2013-01-01

    Exosomes are nanosized membrane-bound vesicles that are released by various cell types and are capable of carrying proteins, lipids and RNAs which can be delivered to recipient cells. Exosomes play a role in intercellular communication and have been described to mediate immunologic information. In this article we report the first isolation and characterization of exosomes from human thymic tissue. Using electron microscopy, particle size determination, density gradient measurement, flow cytometry, proteomic analysis and microRNA profiling we describe the morphology, size, density, protein composition and microRNA content of human thymic exosomes. The thymic exosomes share characteristics with previously described exosomes such as antigen presentation molecules, but they also exhibit thymus specific features regarding surface markers, protein content and microRNA profile. Interestingly, thymic exosomes carry proteins that have a tissue restricted expression in the periphery which may suggest a role in T cell selection and the induction of central tolerance. We speculate that thymic exosomes may provide the means for intercellular information exchange necessary for negative selection and regulatory T cell formation of the developing thymocytes within the human thymic medulla.

  1. Characterization of human thymic exosomes.

    Directory of Open Access Journals (Sweden)

    Gabriel Skogberg

    Full Text Available Exosomes are nanosized membrane-bound vesicles that are released by various cell types and are capable of carrying proteins, lipids and RNAs which can be delivered to recipient cells. Exosomes play a role in intercellular communication and have been described to mediate immunologic information. In this article we report the first isolation and characterization of exosomes from human thymic tissue. Using electron microscopy, particle size determination, density gradient measurement, flow cytometry, proteomic analysis and microRNA profiling we describe the morphology, size, density, protein composition and microRNA content of human thymic exosomes. The thymic exosomes share characteristics with previously described exosomes such as antigen presentation molecules, but they also exhibit thymus specific features regarding surface markers, protein content and microRNA profile. Interestingly, thymic exosomes carry proteins that have a tissue restricted expression in the periphery which may suggest a role in T cell selection and the induction of central tolerance. We speculate that thymic exosomes may provide the means for intercellular information exchange necessary for negative selection and regulatory T cell formation of the developing thymocytes within the human thymic medulla.

  2. Simulation in bronchoscopy: current and future perspectives.

    Science.gov (United States)

    Nilsson, Philip Mørkeberg; Naur, Therese Maria Henriette; Clementsen, Paul Frost; Konge, Lars

    2017-01-01

    To provide an overview of current literature that informs how to approach simulation practice of bronchoscopy and discuss how findings from other simulation research can help inform the use of simulation in bronchoscopy training. We conducted a literature search on simulation training of bronchoscopy and divided relevant studies in three categories: 1) structuring simulation training in bronchoscopy, 2) assessment of competence in bronchoscopy training, and 3) development of cheap alternatives for bronchoscopy simulation. Bronchoscopy simulation is effective, and the training should be structured as distributed practice with mastery learning criteria (ie, training until a certain level of competence is achieved). Dyad practice (training in pairs) is possible and may increase utility of available simulators. Trainee performance should be assessed with assessment tools with established validity. Three-dimensional printing is a promising new technology opening possibilities for developing cheap simulators with innovative features.

  3. Management of liver hydatid cysts - Current perspectives.

    Science.gov (United States)

    Anand, S; Rajagopalan, S; Mohan, Raj

    2012-07-01

    Human hydatid disease or cystic echinococcosis (CE), caused by the larval form of cestode Echinococcus granulosus still continues to a common problem in health care environments as different as Europe/North America and resource poor countries of the South America and the East. The Liver is the most frequently parasatized organ in humans. While ultrasonography remains the main diagnostic tool, computed tomography and serology improve the accuracy of diagnosis in Liver hydatid cysts (LHC). Although surgery is the only modality applicable over the entire spectrum of the disease, systemic chemotherapy and percutaneous drainage have evolved as alternative therapies in the last three decades. Various laparoscopic techniques have also been described for safe and optimal management of this entity. In this paper, we review the current management procedures of LHC with particular emphasis on the evidence base and setting specific problems.

  4. Ketogenic diet in endocrine disorders: Current perspectives.

    Science.gov (United States)

    Gupta, L; Khandelwal, D; Kalra, S; Gupta, P; Dutta, D; Aggarwal, S

    2017-01-01

    Ketogenic diet (KD) is a high-fat, adequate-protein, and low-carbohydrate diet that leads to nutritional ketosis, long known for antiepileptic effects and has been used therapeutically to treat refractory epilepsy. This review attempts to summarize the evidence and clinical application of KD in diabetes, obesity, and other endocrine disorders. KD is usually animal protein based. An empiric vegetarian Indian variant of KD has been provided keeping in mind the Indian food habits. KD has beneficial effects on cardiac ischemic preconditioning, improves oxygenation in patients with respiratory failure, improves glycemic control in diabetics, is associated with significant weight loss, and has a beneficial impact on polycystic ovarian syndrome. Multivitamin supplementations are recommended with KD. Recently, ketones are being proposed as super-metabolic fuel; and KD is currently regarded as apt dietary therapy for "diabesity."

  5. Ketogenic diet in endocrine disorders: Current perspectives

    Directory of Open Access Journals (Sweden)

    L Gupta

    2017-01-01

    Full Text Available Ketogenic diet (KD is a high-fat, adequate-protein, and low-carbohydrate diet that leads to nutritional ketosis, long known for antiepileptic effects and has been used therapeutically to treat refractory epilepsy. This review attempts to summarize the evidence and clinical application of KD in diabetes, obesity, and other endocrine disorders. KD is usually animal protein based. An empiric vegetarian Indian variant of KD has been provided keeping in mind the Indian food habits. KD has beneficial effects on cardiac ischemic preconditioning, improves oxygenation in patients with respiratory failure, improves glycemic control in diabetics, is associated with significant weight loss, and has a beneficial impact on polycystic ovarian syndrome. Multivitamin supplementations are recommended with KD. Recently, ketones are being proposed as super-metabolic fuel; and KD is currently regarded as apt dietary therapy for “diabesity.”

  6. RICH upgrade: Current status and future perspectives

    CERN Document Server

    Pistone, A

    2016-01-01

    The LHCb experiment is dedicated to precision measurements of CP violation and rare decays of B hadrons at the Large Hadron Collider (LHC) at CERN (Geneva). The second long shutdown of the LHC is currently scheduled to begin in 2018. During this period the LHCb experiment with all its sub-detectors will be upgraded in order to run at an instantaneous luminosity of 2×10$^{33}$ cm$^{−2}$s$^{−1}$ and to read out data at a rate of 40MHz into a flexible software-based trigger. The Ring Imaging CHerenkov (RICH) system will require new photon detectors and modifications of the optics of the upstream detector. Tests of the prototype of the smallest constituent of the new RICH system have been performed during testbeam sessions at the Test Beam Facility SPS North Area (CERN) in Autumn 2014.

  7. Ketogenic diet in endocrine disorders: Current perspectives

    Science.gov (United States)

    Gupta, L; Khandelwal, D; Kalra, S; Gupta, P; Dutta, D; Aggarwal, S

    2017-01-01

    Ketogenic diet (KD) is a high-fat, adequate-protein, and low-carbohydrate diet that leads to nutritional ketosis, long known for antiepileptic effects and has been used therapeutically to treat refractory epilepsy. This review attempts to summarize the evidence and clinical application of KD in diabetes, obesity, and other endocrine disorders. KD is usually animal protein based. An empiric vegetarian Indian variant of KD has been provided keeping in mind the Indian food habits. KD has beneficial effects on cardiac ischemic preconditioning, improves oxygenation in patients with respiratory failure, improves glycemic control in diabetics, is associated with significant weight loss, and has a beneficial impact on polycystic ovarian syndrome. Multivitamin supplementations are recommended with KD. Recently, ketones are being proposed as super-metabolic fuel; and KD is currently regarded as apt dietary therapy for “diabesity.” PMID:29022562

  8. Vitamin D and asthma: current perspectives.

    Science.gov (United States)

    Jiao, Junfang; Castro, Mario

    2015-08-01

    To review the current evidence on the relationship between vitamin D and asthma. The rising morbidity and tremendous socioeconomic burden of asthma have prompted efforts to seek modifiable environmental and nutritional factors that contribute to the asthma epidemic. The association between low levels of vitamin D and asthma has been supported by many, but not all observational and epidemiologic studies. Recently, several controlled clinical trials have been undertaken to explore the effect of vitamin D supplementation on asthma control and respiratory tract infections. While some trials support the beneficial role of vitamin D supplementation in reducing asthma severity in children, several trials have found no beneficial role in adults. Given the high prevalence of vitamin D insufficiency in children and adults worldwide and recent randomized controlled trials of vitamin D in asthma, supplementation with vitamin D cannot be recommended as adjunctive therapy for asthma.

  9. DNA origami: a history and current perspective

    Energy Technology Data Exchange (ETDEWEB)

    Nangreave, Jeanette; Han, Dongran; Liu, Yan; Yan, Hao

    Researchers have been using DNA for the rational design and construction of nanoscale objects for nearly 30 years. Recently, ‘scaffolded DNA origami’ has emerged as one of the most promising assembly techniques in DNA nanotechnology with a broad range of applications. In the past two years alone, DNA origami has been used to assemble water-soluble probe tiles for label-free RNA hybridization, to study single-molecule chemical reactions, to probe distance-dependent multivalent ligand–protein binding effects, and to organize a variety of relevant molecules including proteins, carbon nanotubes, and metal nanoparticles. This review will recount the origin, evolution, and current status of this extremely versatile assembly technique.

  10. Simulation in teaching regional anesthesia: current perspectives

    Directory of Open Access Journals (Sweden)

    Udani AD

    2015-08-01

    Full Text Available Ankeet D Udani,1 T Edward Kim,2,3 Steven K Howard,2,3 Edward R Mariano2,3On behalf of the ADAPT (Anesthesiology-Directed Advanced Procedural Training Research Group1Department of Anesthesiology, Duke University School of Medicine, Durham, NC, USA; 2Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA; 3Anesthesiology and Perioperative Care Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USAAbstract: The emerging subspecialty of regional anesthesiology and acute pain medicine represents an opportunity to evaluate critically the current methods of teaching regional anesthesia techniques and the practice of acute pain medicine. To date, there have been a wide variety of simulation applications in this field, and efficacy has largely been assumed. However, a thorough review of the literature reveals that effective teaching strategies, including simulation, in regional anesthesiology and acute pain medicine are not established completely yet. Future research should be directed toward comparative-effectiveness of simulation versus other accepted teaching methods, exploring the combination of procedural training with realistic clinical scenarios, and the application of simulation-based teaching curricula to a wider range of learner, from the student to the practicing physician.Keywords: regional anesthesia, simulation, medical education, ultrasound, nerve block, simulator

  11. Haemovigilance: A Current Update in Indian Perspective.

    Science.gov (United States)

    Mukherjee, Somnath; Maiti, Rituparna

    2016-11-01

    Haemovigilance is an organised scheme of monitoring, identifying, reporting, investigating and analysing adverse events and reactions pertinent to transfusion and manufacturing blood products. This system is also an elemental part of quality control in a blood system, bringing about corrective and preventive measures, and for the perpetual advancement of the quality and safety of blood products and the transfusion process. Nowadays haemovigilance setups have been enforced throughout the globe in most developed countries, to monitor the adverse reactions and episodes associated with blood donations and transfusions. Indian Pharmacopoeia Commission has started a Haemovigilance Program of India (HvPI) in 2012 under its Pharmacovigilance Program of India (PvPI) in collaboration with National Institute of Biologicals, Noida, Uttar Pradesh, under Ministry of Health and Family welfare, Government of India with a primary objective to track adverse reactions/events and incidences associated with blood transfusion and blood product administration and to identify trends, recommend best practices and interventions required to improve patient care and safety. This review article is a detail update of current scenario of haemovigilance in India.

  12. Current perspective of neuroprotection and glaucoma

    Directory of Open Access Journals (Sweden)

    Tian K

    2015-11-01

    Full Text Available Kailin Tian,1,2 Shannon Shibata-Germanos,1 Milena Pahlitzsch,1 M Francesca Cordeiro1,3 1Glaucoma and Retinal Neurodegeneration Research Group, UCL Institute of Ophthalmology, London, UK; 2Eye Centre, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Western Eye Hospital, ICORG, Imperial College NHS Trust, London, UK Abstract: Glaucoma is the second leading cause of blindness worldwide and is most notably characterized by progressive optic nerve atrophy and advancing loss of retinal ganglion cells (RGCs. The main concomitant factor is the elevated intraocular pressure (IOP. Existing treatments are focused generally on lowering IOP. However, both RGC loss and optic nerve atrophy can independently occur with IOP at normal levels. In recent years, there has been substantial progress in the development of neuroprotective therapies for glaucoma in order to restore vital visual function. The present review intends to offer a brief insight into conventional glaucoma treatments and discuss exciting current developments of mostly preclinical data in novel neuroprotective strategies for glaucoma that include recent advances in noninvasive diagnostics going beyond IOP maintenance for an enhanced global view. Such strategies now target RGC loss and optic nerve damage, opening a critical therapeutic window for preventative monitoring and treatment. Keywords: glaucoma, retinal ganglion cell, neuroprotection

  13. Leber hereditary optic neuropathy: current perspectives

    Science.gov (United States)

    Meyerson, Cherise; Van Stavern, Greg; McClelland, Collin

    2015-01-01

    Leber hereditary optic neuropathy (LHON) is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells. PMID:26170609

  14. Genetic cancer vaccines: current status and perspectives.

    Science.gov (United States)

    Aurisicchio, Luigi; Ciliberto, Gennaro

    2012-08-01

    The recent approval of the first therapeutic cancer vaccine by the US Regulatory Agency represents a breakthrough event in the history of cancer treatment. The past scepticism towards this type of therapeutic intervention is now replaced by great expectations. The field is now moving towards the development of alternative vaccination technologies, which are capable of generating stronger, more durable and efficient immune responses against specific tumour-associated antigens (TAAs) in combination with cheaper and more standardised manufacturing. In this context, genetic vaccines are emerging among the most promising methodologies. Several evidences point to combinations of different genetic immunisation modalities (heterologous prime/boost) as a powerful approach to induce superior immune responses and achieve greater clinical efficacy. In this review, we provide an overview of the current status of development of genetic cancer vaccines with particular emphasis on adenoviral vector prime/DNA boost vaccination schedules. We believe that therapeutic genetic cancer vaccines have the strong potential to become an established therapeutic modality for cancer in next coming years, in a manner similar to what have now become monoclonal antibodies.

  15. Leber hereditary optic neuropathy: current perspectives

    Directory of Open Access Journals (Sweden)

    Meyerson C

    2015-06-01

    Full Text Available Cherise Meyerson, Greg Van Stavern, Collin McClelland Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO, USA Abstract: Leber hereditary optic neuropathy (LHON is one of the most common inherited optic neuropathies causing bilateral central vision loss. The disorder results from point mutations in mitochondrial DNA and subsequent mitochondrial dysfunction. The primary cell type that is lost in LHON is the retinal ganglion cell, which is highly susceptible to disrupted ATP production and oxidative stress. Inheritance of LHON follows that of mitochondrial genetics, and it has a highly variable clinical phenotype, as other genetic and environmental factors also play a role. Although LHON usually presents with isolated vision loss, some patients suffer other neurological sequelae. For ill-defined reasons, male LHON mutation carriers are more affected than females. Most LHON patients remain legally blind, but a small proportion can experience spontaneous partial recovery, often within the first year of symptom onset. Unfortunately, at this time there are no established curative interventions and treatment is largely supportive. Patients should be offered low vision services and counseled on mitigating risk factors for additional vision loss, such as smoking and consuming alcohol. Encouraging treatments currently undergoing investigation includes ubiquinone analogs, such as idebenone, as well as gene therapy and stem cells to restore ATP synthesis and provide neuroprotection to surviving retinal ganglion cells. Keywords: Leber hereditary optic neuropathy, mitochondria, neuro-ophthalmology, mitochondrial DNA

  16. Management of refractory ischemic priapism: current perspectives

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    Capece M

    2017-08-01

    Full Text Available Marco Capece,1 Arianna Gillo,2 Andrea Cocci,3 Giulio Garaffa,1 Massimiliano Timpano,4 Marco Falcone4 1The Institute of Urology, University College of London Hospital (UCLH, London, UK; 2Department of Urology, “Umberto Parini” Hospital, Aosta, 3Department of Urology, Careggi Hospital, Firenze, 4Department of Urology, University of Turin, Città della Salute e della Scienza, Turin, Italy Objectives: The aim of the present manuscript is to review the current literature on priapism, focusing on the state-of-the-art knowledge of both the diagnosis and the treatment of the refractory ischemic priapism (IP.Methods: Pubmed and EMBASE search engines were used to search for words “priapism”, “refractory priapism”, “penile prosthesis”, “diagnosis priapism”, “priapism treatment”, “penile fibrosis”, “priapism therapy”. All the studies were carefully examined by the authors and then included in the review.Results: First-line treatment involves ejaculation, physical exercise and cold shower followed by corporal blood aspiration and injection of α-adrenoceptor agonists. Subsequently, a distal or proximal shunt may be considered. If none of the treatment is effective or the priapism episode lasts >48 hours penile prosthesis implantation could be the only option to solve the priapism and treat the ongoing erectile dysfunction.Conclusion: The management of IP is to achieve detumescence of persistent penile erection and to preserve erectile function after resolution of the priapic episode. On the other hand, penile fibrosis and following shortening should be prevented. Early penile prosthesis implantation in patients with refractory IP is able to solve both the priapic episode and prevent the otherwise certain penile shortening. Penile prosthesis implantation is the actual gold standard of care in cases of refractory IP. Keywords: priapism, ischemic priapism, penile fibrosis, penile prosthesis, shunt 

  17. 3,4-methylenedioxymethamphetamine (MDMA: current perspectives

    Directory of Open Access Journals (Sweden)

    Meyer JS

    2013-11-01

    . MDMA/ecstasy-dependent patients are treated with standard addiction programs, since there are no specific programs for this substance and no proven medications. Finally, even though MDMA is listed as a Schedule I compound by the Drug Enforcement Agency, MDMA-assisted psychotherapy for patients with chronic, treatment-resistant posttraumatic stress disorder is currently under investigation. Initial results show efficacy for this treatment approach, although considerably more research must be performed to confirm such efficacy and to ensure that the benefits of MDMA-assisted therapy outweigh the risks to the patients. Keywords: MDMA, ecstasy, mood, cognition, neurotoxicity, dependence, PTSD

  18. Limbal stem cell transplantation: current perspectives

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    Atallah MR

    2016-04-01

    Full Text Available Marwan Raymond Atallah, Sotiria Palioura, Victor L Perez, Guillermo Amescua Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Abstract: Regeneration of the corneal surface after an epithelial insult involves division, migration, and maturation of a specialized group of stem cells located in the limbus. Several insults, both intrinsic and extrinsic, can precipitate destruction of the delicate microenvironment of these cells, resulting in limbal stem cell deficiency (LSCD. In such cases, reepithelialization fails and conjunctival epithelium extends across the limbus, leading to vascularization, persistent epithelial defects, and chronic inflammation. In partial LSCD, conjunctival epitheliectomy, coupled with amniotic membrane transplantation, could be sufficient to restore a healthy surface. In more severe cases and in total LSCD, stem cell transplantation is currently the best curative option. Before any attempts are considered to perform a limbal stem cell transplantation procedure, the ocular surface must be optimized by controlling causative factors and comorbid conditions. These factors include adequate eyelid function or exposure, control of the ocular surface inflammatory status, and a well-lubricated ocular surface. In cases of unilateral LSCD, stem cells can be obtained from the contralateral eye. Newer techniques aim at expanding cells in vitro or in vivo in order to decrease the need for large limbal resection that may jeopardize the “healthy” eye. Patients with bilateral disease can be treated using allogeneic tissue in combination with systemic immunosuppressive therapy. Another emerging option for this subset of patients is the use of noncorneal cells such as mucosal grafts. Finally, the use of keratoprosthesis is reserved for patients who are not candidates for any of the aforementioned options, wherein the choice of the type of keratoprosthesis depends on

  19. 3,4-methylenedioxymethamphetamine (MDMA): current perspectives.

    Science.gov (United States)

    Meyer, Jerrold S

    2013-01-01

    medications. Finally, even though MDMA is listed as a Schedule I compound by the Drug Enforcement Agency, MDMA-assisted psychotherapy for patients with chronic, treatment-resistant posttraumatic stress disorder is currently under investigation. Initial results show efficacy for this treatment approach, although considerably more research must be performed to confirm such efficacy and to ensure that the benefits of MDMA-assisted therapy outweigh the risks to the patients.

  20. Structural Learning Theory: Current Status and New Perspectives.

    Science.gov (United States)

    Scandura, Joseph M.

    2001-01-01

    Presents the current status and new perspectives on the Structured Learning Theory (SLT), with special consideration given to how SLT has been influenced by recent research in software engineering. Topics include theoretical constructs; content domains; structural analysis; cognition; assessing behavior potential; and teaching and learning issues,…

  1. Medicinal mushroom science: Current perspectives, advances, evidences, and challenges

    OpenAIRE

    Solomon P. Wasser

    2014-01-01

    The main target of the present review is to draw attention to the current perspectives, advances, evidences, challenges, and future development of medicinal mushroom science in the 21 st century. Medicinal mushrooms and fungi are thought to possess approximately 130 medicinal functions, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, anti-hypercholesterolemic, antiviral, antibacterial, anti-parasitic, antifungal, detoxification, hepatoprotective, and an...

  2. Shikonin Inhibits the Proliferation of Human Breast Cancer Cells by Reducing Tumor-Derived Exosomes

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    Yao Wei

    2016-06-01

    Full Text Available Shikonin is a naphthoquinone isolated from the traditional Chinese medicine Lithospermum. It has been used in the treatment of various tumors. However, the effects of shikonin on such diseases have not been fully elucidated. In the present study, we detected the exosome release of a breast cancer cell line (MCF-7 with shikonin treatment and found a positive relationship between the level of secreted exosomes and cell proliferation. We next analyzed miRNA profiles in MCF-7 cells and exosomes and found that some miRNAs are specifically sorted and abundant in exosomes. Knockdown of the most abundant miRNAs in exosomes and the MCF-7 proliferation assay showed that miR-128 in exosomes negatively regulates the level of Bax in MCF-7 recipient cells and inhibits cell proliferation. These results show that shikonin inhibits the proliferation of MCF-7 cells through reducing tumor-derived exosomal miR-128. The current study suggests that shikonin suppresses MCF-7 growth by the inhibition of exosome release.

  3. Sialoglycoproteins and N-glycans from secreted exosomes of ovarian carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Cristina Escrevente

    Full Text Available Exosomes consist of vesicles that are secreted by several human cells, including tumor cells and neurons, and they are found in several biological fluids. Exosomes have characteristic protein and lipid composition, however, the results concerning glycoprotein composition and glycosylation are scarce. Here, protein glycosylation of exosomes from ovarian carcinoma SKOV3 cells has been studied by lectin blotting, NP-HPLC analysis of 2-aminobenzamide labeled glycans and mass spectrometry. An abundant sialoglycoprotein was found enriched in exosomes and it was identified by peptide mass fingerprinting and immunoblot as the galectin-3-binding protein (LGALS3BP. Exosomes were found to contain predominantly complex glycans of the di-, tri-, and tetraantennary type with or without proximal fucose and also high mannose glycans. Diantennary glycans containing bisecting N-acetylglucosamine were also detected. This work provides detailed information about glycoprotein and N-glycan composition of exosomes from ovarian cancer cells, furthermore it opens novel perspectives to further explore the functional role of glycans in the biology of exosomes.

  4. Exosome platform for diagnosis and monitoring of traumatic brain injury

    Science.gov (United States)

    Taylor, Douglas D.; Gercel-Taylor, Cicek

    2014-01-01

    We have previously demonstrated the release of membranous structures by cells into their extracellular environment, which are termed exosomes, microvesicles or extracellular vesicles depending on specific characteristics, including size, composition and biogenesis pathway. With activation, injury, stress, transformation or infection, cells express proteins and RNAs associated with the cellular responses to these events. The exosomes released by these cells can exhibit an array of proteins, lipids and nucleic acids linked to these physiologic events. This review focuses on exosomes associated with traumatic brain injury, which may be both diagnostic and a causative factor in the progression of the injury. Based on current data, exosomes play essential roles as conveyers of intercellular communication and mediators of many of the pathological conditions associated with development, progression and therapeutic failures and cellular stress in a variety of pathologic conditions. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodelling, signal pathway activation through growth factor/receptor transfer, chemoresistance, immunologic activation and genetic exchange. These circulating exosomes not only represent a central mediator of the pro-inflammatory microenvironment linked with secondary brain injury, but their presence in the peripheral circulation may serve as a surrogate for biopsies, enabling real-time diagnosis and monitoring of neurodegenerative progression. PMID:25135964

  5. Circulating exosomes as new biomarkers for brain disease and injury

    Science.gov (United States)

    Graner, Michael W.; Epple, Laura M.; Dusto, Nathaniel L.; Lencioni, Alex M.; Nega, Meheret; Herring, Matthew; Winston, Ben; Madsen, Helen; Bemis, Lynne T.; Anchordoquy, Thomas J.

    2013-05-01

    Brain diseases such as cancers, neurodegenerative disorders, or trauma are frequently diagnosed with imaging modalities and sometimes with intracranial biopsies. Treatment response is similarly monitored, along with clinical indications. While these technologies provide important windows into the disease state, they fail to provide us a detailed molecular portrait of the disease and of the changes taking place during therapy. Exosomes are virus-sized nanovesicles derived from the endosomal system and are released extracellularly from essentially all cell types. Exosomes contain intracellular entities (proteins, nucleic acids, metabolites), membrane proteins and lipids, and even extracellular proteins bound to them. Exosomes may be considered as mini-surrogates of their cells of origin, with some content common to all cells/exosomes, but some of the content would be cell-specific. These vesicles are found in all biofluids in humans, and are thus accessible to "liquid biopsy" with harvest of vesicles from such fluids. Current challenges are to identify disease-related markers or panels of markers to distinguish the disease state. Here we will show examples of brain tumor markers found in/on exosomes from cell culture and patient sera, and we will suggest that aspects of the biology of disease may have a relevant place in the search for biomarkers.

  6. Toward Exosome-Based Therapeutics: Isolation, Heterogeneity, and Fit-for-Purpose Potency

    Directory of Open Access Journals (Sweden)

    Gareth R. Willis

    2017-10-01

    scale-up and good manufacturing practice compliance have complicated smooth and timely transition to clinical development. In this manuscript, we focus on cell culture conditions, exosome harvesting, dosage, and exosome potency, providing some empirical guidance and perspectives on the challenges in bringing exosome-based therapies to clinic.

  7. Exosomes: A Novel Strategy for Treatment and Prevention of Diseases

    Directory of Open Access Journals (Sweden)

    Jiaqi Wang

    2017-06-01

    Full Text Available An “exosome” is a nanoscale membrane vesicle derived from cell endocytosis that functions as an important intercellular communication mediator regulating the exchange of proteins and genetic materials between donor and surrounding cells. Exosomes secreted by normal and cancer cells participate in tumor initiation, progression, invasion, and metastasis. Furthermore, immune cells and cancer cells exert a two-way bidirectional regulatory effect on tumor immunity by exchanging exosomes. Current studies on exosomes have further expanded their known functions in physiological and pathological processes. The purpose of this review is to describe their discovery and biological functions in the context of their enormous potential in the clinical diagnosis, prevention, and treatment of cancer as well as bacterial and viral infectious diseases.

  8. Post isolation modification of exosomes for nanomedicine applications

    Science.gov (United States)

    Hood, Joshua L

    2016-01-01

    Exosomes are extracellular nanovesicles. They innately possess ideal structural and biocompatible nanocarrier properties. Exosome components can be engineered at the cellular level. Alternatively, when exosome source cells are unavailable for customized exosome production, exosomes derived from a variety of biological origins can be modified post isolation which is the focus of this article. Modification of exosome surface structures allows for exosome imaging and tracking in vivo. Exosome membranes can be loaded with hydrophobic therapeutics to increase drug stability and efficacy. Hydrophilic therapeutics such as RNA can be encapsulated in exosomes to improve cellular delivery. Despite advances in post isolation exosome modification strategies, many challenges to effectively harnessing their therapeutic potential remain. Future topics of exploration include: matching exosome subtypes with nanomedicine applications, optimizing exosomal nanocarrier formulation and investigating how modified exosomes interface with the immune system. Research into these areas will greatly facilitate personalized exosome-based nanomedicine endeavors. PMID:27348448

  9. Exosomes Derived from Dendritic Cells Treated with Schistosoma japonicum Soluble Egg Antigen Attenuate DSS-Induced Colitis

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    Lifu Wang

    2017-09-01

    Full Text Available Exosomes are 30–150 nm small membrane vesicles that are released into the extracellular medium via cells that function as a mode of intercellular communication. Dendritic cell (DC-derived exosomes modulate immune responses and prevent the development of autoimmune diseases. Moreover, Schistosoma japonicum eggs show modulatory effects in a mouse model of colitis. Therefore, we hypothesized that exosomes derived from DCs treated with S. japonicum soluble eggs antigen (SEA; SEA-treated DC exosomes would be useful for treating inflammatory bowel disease (IBD. Exosomes were purified from the supernatant of DCs treated or untreated with SEA and identified via transmission electron microscopy, western blotting and NanoSight. Acute colitis was induced via the administration of dextran sulfate sodium (DSS in drinking water (5.0%, wt/vol. Treatment with exosomes was conducted via intraperitoneal injection (i.p.; 50 μg per mouse from day 0 to day 6. Clinical scores were calculated based on weight loss, stool type, and bleeding. Colon length was measured as an indirect marker of inflammation, and colon macroscopic characteristics were determined. Body weight loss and the disease activity index of DSS-induced colitis mice decreased significantly following treatment with SEA-treated DC exosomes. Moreover, the colon lengths of SEA-treated DC exosomes treated colitis mice improved, and their mean colon macroscopic scores decreased. In addition, histologic examinations and histological scores showed that SEA-treated DC exosomes prevented colon damage in acute DSS-induced colitis mice. These results indicate that SEA-treated DC exosomes attenuate the severity of acute DSS-induced colitis mice more effectively than DC exosomes. The current work suggests that SEA-treated DC exosomes may be useful as a new approach to treat IBD.

  10. Exosomes and Exosomal miRNA in Respiratory Diseases

    Directory of Open Access Journals (Sweden)

    Shamila D. Alipoor

    2016-01-01

    Full Text Available Exosomes are nanosized vesicles released from every cell in the body including those in the respiratory tract and lungs. They are found in most body fluids and contain a number of different biomolecules including proteins, lipids, and both mRNA and noncoding RNAs. Since they can release their contents, particularly miRNAs, to both neighboring and distal cells, they are considered important in cell-cell communication. Recent evidence has shown their possible importance in the pathogenesis of several pulmonary diseases. The differential expression of exosomes and of exosomal miRNAs in disease has driven their promise as biomarkers of disease enabling noninvasive clinical diagnosis in addition to their use as therapeutic tools. In this review, we summarize recent advances in this area as applicable to pulmonary diseases.

  11. MicroRNA profiling in kidney disease: Plasma versus plasma-derived exosomes.

    Science.gov (United States)

    Xie, Jeffrey X; Fan, Xiaoming; Drummond, Christopher A; Majumder, Reetam; Xie, Yanmei; Chen, Tian; Liu, Lijun; Haller, Steven T; Brewster, Pamela S; Dworkin, Lance D; Cooper, Christopher J; Tian, Jiang

    2017-09-05

    Liquid biopsies have advanced rapidly in recent years for use in diagnostic and prognostic applications. One important aspect of this advancement is the growth in our understanding of microRNA (miRNA) biology. The measurement of miRNAs packaged within exosomes, which are constantly released into the blood stream, may reflect pathological changes within the body. The current study performed miRNA profiling using plasma and plasma-derived exosome samples from two animal models of kidney disease, the 5/6th partial nephrectomy (PNx) and two-kidney-one-clip (2K1C) models. The RT-qPCR-based profiling results revealed that the overall miRNA expression level was much higher in plasma than in plasma-derived exosomes. With 200μl of either plasma or exosomes derived from the same volume of plasma, 629 out of 665 total miRNAs analyzed were detectable in plasma samples from sham-operated rats, while only 403 were detectable in exosomes with a cutoff value set at 35cycles. Moreover, the average miRNA expression level in plasma was about 16-fold higher than that in exosomes. We also found a select subset of miRNAs that were enriched within exosomes. The number of detectable miRNAs from plasma-derived exosomes was increased in rats subjected to PNx or 2K1C surgery compared to sham-operated animals. Importantly, we found that the changes of individual miRNAs measured in plasma had very poor concordance with that measured in plasma-derived exosomes in both animal models, suggesting that miRNAs in plasma and plasma-derived exosomes are differentially regulated in these disease conditions. Interestingly, PNx and 2K1C surgeries induced similar changes in miRNA expression, implying that common pathways were activated in these two disease models. Pathway analyses using DIANA-miRPath v3.0 showed that significantly changed exosomal miRNAs were associated with extracellular matrix (ECM) receptor interaction and mucin type-O-glycan synthesis pathways, which are related with tissue fibrosis

  12. MicroRNAs of parasites: current status and future perspectives.

    Science.gov (United States)

    Liu, Quan; Tuo, Wenbin; Gao, Hongwei; Zhu, Xing-Quan

    2010-08-01

    MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs regulating gene expression in eukaryotes at the post-transcriptional level. The complex life cycles of parasites may require the ability to respond to environmental and developmental signals through miRNA-mediated gene expression. Over the past 17 years, thousands of miRNAs have been identified in the nematode Caenorhabditis elegans and other parasites. Here, we review the current status and potential functions of miRNAs in protozoan, helminths, and arthropods, and propose some perspectives for future studies.

  13. [Multilateral Strategies Utilizing Exosomes for Cancer Therapy].

    Science.gov (United States)

    Nishida-Aoki, Nao; Ochiya, Takahiro

    2017-05-01

    Exosomes are nano-sized extracellular vesicles which transfer their components such as RNA, DNA, and proteins from one cell to another cell. The components are released to the cytoplasm of the recipient cells, having an effect on the cells. Cancerderived exosomes promote cancer progression, invasion, gain of drug resistance, and metastasis. Recently, according to their characteristics, it is expected to apply exosomes to cancer therapies, such as utilizing exosomes as drug delivery systems(DDS) for anticancer drugs and as cancer vaccines to enhance immunity to cancer cells. More, as the cancer-derived exosomes have cancer-promoting effects on multiple stages, inhibiting the function of the cancer-derived exosomes would be helpful to cancer therapies by suppressing cancer progression. DDS and cancer vaccines utilizing exosomes are now undergoing clinical studies, although DDS is suffering from loading efficiency. Treatments by inhibiting the functions of cancer-derived exosomes have still only few reports at experimental levels. Recently, we showed in a mouse model that disruption of cancer-derived exosomes by antibodies could suppress lung metastasis of the human breast cancer cells. Exosomes will provide us the multiple strategies to fight with cancer, which can be applied to cancers from many organs. It is important to confirm safety and overcome technical problems to bring exosomes in practical use.

  14. Stem Cell-Derived Exosomes: A Potential Alternative Therapeutic Agent in Orthopaedics

    Directory of Open Access Journals (Sweden)

    John Burke

    2016-01-01

    Full Text Available Within the field of regenerative medicine, many have sought to use stem cells as a promising way to heal human tissue; however, in the past few years, exosomes (packaged vesicles released from cells have shown more exciting promise. Specifically, stem cell-derived exosomes have demonstrated great ability to provide therapeutical benefits. Exosomal products can include miRNA, other genetic products, proteins, and various factors. They are released from cells in a paracrine fashion in order to combat local cellular stress. Because of this, there are vast benefits that medicine can obtain from stem cell-derived exosomes. If exosomes could be extracted from stem cells in an efficient manner and packaged with particular regenerative products, then diseases such as rheumatoid arthritis, osteoarthritis, bone fractures, and other maladies could be treated with cell-free regenerative medicine via exosomes. Many advances must be made to get to this point, and the following review highlights the current advances of stem cell-derived exosomes with particular attention to regenerative medicine in orthopaedics.

  15. ExoCarta: A Web-Based Compendium of Exosomal Cargo.

    Science.gov (United States)

    Keerthikumar, Shivakumar; Chisanga, David; Ariyaratne, Dinuka; Al Saffar, Haidar; Anand, Sushma; Zhao, Kening; Samuel, Monisha; Pathan, Mohashin; Jois, Markandeya; Chilamkurti, Naveen; Gangoda, Lahiru; Mathivanan, Suresh

    2016-02-22

    Exosomes are membranous vesicles that are released by a variety of cells into the extracellular microenvironment and are implicated in intercellular communication. As exosomes contain RNA, proteins and lipids, there is a significant interest in characterizing the molecular cargo of exosomes. Here, we describe ExoCarta (http://www.exocarta.org), a manually curated Web-based compendium of exosomal proteins, RNAs and lipids. Since its inception, the database has been highly accessed (>54,000 visitors from 135 countries). The current version of ExoCarta hosts 41,860 proteins, >7540 RNA and 1116 lipid molecules from more than 286 exosomal studies annotated with International Society for Extracellular Vesicles minimal experimental requirements for definition of extracellular vesicles. Besides, ExoCarta features dynamic protein-protein interaction networks and biological pathways of exosomal proteins. Users can download most often identified exosomal proteins based on the number of studies. The downloaded files can further be imported directly into FunRich (http://www.funrich.org) tool for additional functional enrichment and interaction network analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Polycystic ovary syndrome: current status and future perspective

    Science.gov (United States)

    Barthelmess, Erin K.; Naz, Rajesh K.

    2015-01-01

    Polycystic ovary syndrome (PCOS) is a widespread reproductive disorder that encompasses many associated health conditions and has an impact on various metabolic processes. PCOS is depicted by hyperandrogenism, polycystic ovaries, and anovulation. It increases the risk of insulin resistance (IR), type 2 diabetes, obesity, and cardiovascular disease. The etiology of the disease remains unclear, and the subjective phenotype makes a united diagnosis difficult among physicians. It seems to be a familial genetic syndrome caused by a combination of environmental and genetic factors. It can be linked with metabolic disorders in first-degree family members. PCOS is the cause of up to 30% of infertility in couples seeking treatment. Currently, there is no cure for PCOS. Despite the growing incidence of this syndrome, limited research has been done that encompasses the entirety of PCOS spectrum. In this review, the current status and possible future perspective will be discussed. PMID:24389146

  17. Polycystic ovary syndrome: current status and future perspective.

    Science.gov (United States)

    Barthelmess, Erin K; Naz, Rajesh K

    2014-01-01

    Polycystic ovary syndrome (PCOS) is a widespread reproductive disorder that encompasses many associated health conditions and has an impact on various metabolic processes. PCOS is depicted by hyperandrogenism, polycystic ovaries, and anovulation. It increases the risk of insulin resistance (IR), type 2 diabetes, obesity, and cardiovascular disease. The etiology of the disease remains unclear, and the subjective phenotype makes a united diagnosis difficult among physicians. It seems to be a familial genetic syndrome caused by a combination of environmental and genetic factors. It can be linked with metabolic disorders in first-degree family members. PCOS is the cause of up to 30% of infertility in couples seeking treatment. Currently, there is no cure for PCOS. Despite the growing incidence of this syndrome, limited research has been done that encompasses the entirety of PCOS spectrum. In this review, the current status and possible future perspective will be discussed.

  18. SMALL VESICLES, BIG VEHICLES: EXOSOMES.

    Directory of Open Access Journals (Sweden)

    Saiz-Lopez P

    2016-09-01

    Full Text Available Exosomes are small membranous vesicles released by different cell types. Since their discovery, they have evolved from being considered simple vehicles for the liberation of cellular wastes, to become one of the most promising fields in the area of biomedical research, and more specifically in oncology, since the different malignant tumors release exosomes to all biological fluids, being involved in various functions of the neoplastic process. At present, it is possible to study these vesicles by minimally invasive techniques in patients, which approach us to obtain a more detailed diagnosis and prognosis, as well as to the discovery of new antitumoral therapies

  19. Phenotypic modulation of auto-reactive cells by insertion of tolerogenic molecules via MSC-derived exosomes.

    Science.gov (United States)

    Mokarizadeh, Aram; Delirezh, Nowruz; Morshedi, Ahhmad; Mosayebi, Ghasem; Farshid, Amir-Abbas; Dalir-Naghadeh, Bahram

    2012-01-01

    Auto-reactive cells-mediated immune responses are responsible for the current tissue damages during autoimmunity. Accordingly, functional modulation of auto-reactive cells has been a pivotal aim in many of recent studies. In the current study, we investigated the possibility for insertion of regulatory molecules onto auto-reactive cells through exosomal nano-shuttles as a novel approach for phenotype modification of auto-reactive cells. The exosomes were isolated from supernatant of mesenchymal stem cells culture. Resultant exosomes co-cultured with lymphocytes were harvested from established EAE mice in the presence of antigenic MOG35-55 peptide. After 24 hr, insertion of exosomal tolerogenic molecules (PD-L1, TGF-β, galectin-1) onto auto-reactive cells were explored through flow cytometry. The potency of exosomal inserted membrane molecules to modulate phenotype of auto-reactive lymphocytes was assessed upon ELISA test for their-derived cytokines IFN-γ and IL-17. Incorporation of exosomal molecules into lymohocytes' membrane was confirmed by flow cytometric analyses for surface levels of mentioned molecules. Additionally, the decreased secretion of IFN-γ and IL-17 were detected in exosome pre-treated lymphocytes upon stimulation with MOG peptide. Mesenchymal stem cells -derived exosomes showed to be efficient organelles for insertion of bioactive tolerogenic molecules onto auto-reactive cells and modulation of their phenotypes.

  20. Exosomes and Exosomal miRNA in Respiratory Diseases

    NARCIS (Netherlands)

    Alipoor, Shamila D.; Mortaz, Esmaeil|info:eu-repo/dai/nl/29141320X; Garssen, Johan|info:eu-repo/dai/nl/086369962; Movassaghi, Masoud; Mirsaeidi, Mehdi; Adcock, Ian M.

    Exosomes are nanosized vesicles released from every cell in the body including those in the respiratory tract and lungs. They are found in most body fluids and contain a number of different biomolecules including proteins, lipids, and both mRNA and noncoding RNAs. Since they can release their

  1. Exosomal non-coding RNAs: a promising cancer biomarker.

    Science.gov (United States)

    Yang, Huan; Fu, Hailong; Xu, Wenrong; Zhang, Xu

    2016-12-01

    Novel and non-invasive biomarkers are urgently needed for early detection of cancer. Exosomes are nano-sized particles released by cells and contain various bioactive molecules including proteins, DNA, mRNAs, and non-coding RNAs. Increasing evidence suggests that exosomes play critical roles in tumorigenesis, tumor growth, metastasis, and therapy resistance. Exosomes could be readily accessible in nearly all the body fluids. The altered production of exosomes and aberrant expression of exosomal contents could reflect the pathological state of the body, indicating that exosomes and exosomal contents can be utilized as novel cancer biomarkers. Herein, we review the basic properties of exosomes, the functional roles of exosomes in cancer, and the methods of detecting exosomes and exosomal contents. In particular, we highlight the clinical values of exosomal non-coding RNAs in cancer diagnosis and prognosis.

  2. Exosomes in the nose induce immune cell trafficking and harbour an altered protein cargo in chronic airway inflammation.

    Science.gov (United States)

    Lässer, Cecilia; O'Neil, Serena E; Shelke, Ganesh V; Sihlbom, Carina; Hansson, Sara F; Gho, Yong Song; Lundbäck, Bo; Lötvall, Jan

    2016-06-20

    Exosomes are nano-sized extracellular vesicles participating in cell-to-cell communication both in health and disease. However, the knowledge about the functions and molecular composition of exosomes in the upper airways is limited. The aim of the current study was therefore to determine whether nasal exosomes can influence inflammatory cells and to establish the proteome of nasal lavage fluid-derived exosomes in healthy subjects, as well as its alterations in individuals with chronic airway inflammatory diseases [asthma and chronic rhinosinusitis (CRS)]. Nasal lavage fluid was collected from 14 healthy subjects, 15 subjects with asthma and 13 subjects with asthma/CRS. Exosomes were isolated with differential centrifugation and the proteome was analysed by LC-MS/MS with the application of two exclusion lists as well as using quantitative proteomics. Ingenuity Pathways Analysis and GO Term finder was used to predict the functions associated with the exosomal proteome and a migration assay was used to analyse the effect on immune cells by nasal exosomes. Firstly, we demonstrate that nasal exosomes can induce migration of several immune cells, such as monocytes, neutrophils and NK cells in vitro. Secondly, a mass spectrometry approach, with the application of exclusion lists, was utilised to generate a comprehensive protein inventory of the exosomes from healthy subjects. The use of exclusion lists resulted in the identification of ~15 % additional proteins, and increased the confidence in ~20 % of identified proteins. In total, 604 proteins were identified in nasal exosomes and the nasal exosomal proteome showed strong associations with immune-related functions, such as immune cell trafficking. Thirdly, a quantitative proteomics approach was used to determine alterations in the exosome proteome as a result of airway inflammatory disease. Serum-associated proteins and mucins were more abundant in the exosomes from subjects with respiratory diseases compared to

  3. Identification and Reconstruction of Prostate Tumor-Suppressing Exosomes for Therapeutic Applications

    Science.gov (United States)

    2016-03-01

    Fevrier B, Raposo G. Exosomes: endosomal-derived vesicles shipping extracellular messages. Current opinion in cell biology 2004;16(4):415-21. 2. Record...overarching challenges of PCRP is to develop effective treatments for advanced prostate cancer. As nano-meter sized vesicles released by many cell types...meter sized vesicles released by many cell types (1). Comprised of lipids, proteins, coding and non-coding RNAs, exosomes serve as cargo carriers

  4. Exosomes: Implications in HIV-1 Pathogenesis

    Science.gov (United States)

    Madison, Marisa N.; Okeoma, Chioma M.

    2015-01-01

    Exosomes are membranous nanovesicles of endocytic origin that carry host and pathogen derived genomic, proteomic, and lipid cargos. Exosomes are secreted by most cell types into the extracellular milieu and are subsequently internalized by recipient cells. Upon internalization, exosomes condition recipient cells by donating their cargos and/or activating various signal transduction pathways, consequently regulating physiological and pathophysiological processes. The role of exosomes in viral pathogenesis, especially human immunodeficiency virus type 1 [HIV-1] is beginning to unravel. Recent research reports suggest that exosomes from various sources play important but different roles in the pathogenesis of HIV-1. From these reports, it appears that the source of exosomes is the defining factor for the exosomal effect on HIV-1. In this review, we will describe how HIV-1 infection is modulated by exosomes and in turn how exosomes are targeted by HIV-1 factors. Finally, we will discuss potentially emerging therapeutic options based on exosomal cargos that may have promise in preventing HIV-1 transmission. PMID:26205405

  5. Current Status and Perspectives of Forestry Entrepreneurship in Croatia

    Directory of Open Access Journals (Sweden)

    Mario Šporčić

    2017-01-01

    Full Text Available Background and Purpose: The relevance and importance of forestry entrepreneurship is constantly increasing, especially in countries with high transition dynamics in forestry sector. In Croatia, forestry entrepreneurs have in short time become an indispensable part in the performing of harvesting and other types of forestry operations. This paper presents the current status and perspectives of forestry entrepreneurship in Croatia. Materials and Methods: Based on the analysis of the available data from various sources (normative state acts, Forestry Chamber’s official registries, databases and documents, state forestry company business reports etc., this paper provides an overview of the legal and institutional framework for the activities of private entrepreneurs in Croatian forestry with particular attention to licensing forestry contractors and the role of the Croatian Chamber of Forest and Wood Technology Engineers (Forestry Chamber. Results and Conclusions: The paper explains the activities, tasks, organization structure and formal bodies of the Forestry Chamber. The licensing model is also presented together with the formal criteria and minimum conditions which forestry entrepreneurs have to fulfill in order to acquire a license for forest work operations. Structural characteristics and the profile of forestry entrepreneurs is given by the number, size and type of business, the type of forest operations for which they are licensed, and the volume of work that they are performing for Croatian Forests Ltd, the state forest company. Finally, the paper includes some reflections on the perspectives and possibilities for improving the status of entrepreneurship in Croatian forestry.

  6. Factors affecting the regulation of pacing: current perspectives

    Directory of Open Access Journals (Sweden)

    Mauger AR

    2014-09-01

    Full Text Available Alexis R Mauger Endurance Research Group, School of Sport and Exercise Sciences, Faculty of Science, University of Kent, Chatham, UK Abstract: During prolonged dynamic and rhythmic exercise, muscular pain and discomfort arises as a result of an increased concentration of deleterious metabolites. Sensed by peripheral nociceptors and transmitted via afferent feedback to the brain, this provides important information regarding the physiological state of the muscle. These sensations ultimately contribute to what is termed "exercise-induced pain". Despite being well recognized by athletes and coaches, and suggested to be integral to exercise performance, this construct has largely escaped attention in experimental work. This perspective article highlights the current understanding of pacing in endurance performance, and the causes of exercise-induced pain. A new perspective is described, which proposes how exercise-induced pain may be a contributing factor in helping individuals to regulate their work rate during exercise and thus provides an important construct in pacing. Keywords: pain, exercise-induced pain, discomfort, exercise performance, self-paced

  7. Exosomes and their Application in Biomedical Field: Difficulties and Advantages.

    Science.gov (United States)

    Rezaie, Jafar; Ajezi, Saeed; Avci, Çığır Biray; Karimipour, Mohammad; Geranmayeh, Mohammad Hossein; Nourazarian, Alireza; Sokullu, Emel; Rezabakhsh, Aysa; Rahbarghazi, Reza

    2017-05-11

    The science of gene therapy has experienced a controversial history. At first, the initial concept that various disorders become curable by gene transferring was very exciting and challengeable. However, the problems and difficulties related to emerging techniques and unwanted side effects seen in some patients who have undergone gene therapy make some questions against the safety of novel molecular medicine approach. In line with this statement, discovery and developing a good bio-vector possessing low toxicity and high efficiency rate are the most important issues in gene therapy field. Introducing exosomes as vectors for gene delivery gives us a new opportunity in gene-based therapy. Exosomes, ranging from 30 to 120 nm in diameter, have unique lipid and protein composition. These nanostructures participate in cell-to-cell cross-talk, regulation of immune system, and the transport of genetic material. Besides the inherent potency of exosomes in gene therapy, a better understanding of their biology, characteristics, production, targeting, and cargo loading still need to be elucidated. In the current review, we exclusively focused on the various facets of exosomes and their importance as a bio-shuttle in gene therapy.

  8. Exosomic microRNAs in the tumor microenvironment

    Directory of Open Access Journals (Sweden)

    Paolo eNeviani

    2015-07-01

    Full Text Available Dissecting the cross talk between tumor cells and tumor microenvironment is quickly becoming the new frontier in cancer research. It is now widely accepted that cancer cells can exert a profound influence over their surroundings, by changing the microenvironment from a normal to a tumor-supportive state that allows for sustained tumor-growth, invasion and drug-resistance. Extracellular vesicles, especially exosomes, are recognized as a new category of intercellular communicator and they are emerging as of primary importance in controlling the interplay between the tumor and its environment. Exosomes derived from cancer cells or from cells of the tumor microenvironment allow for the horizontal transfer of information by virtue of their cargo, made of functional proteins and nucleic acids that are specifically sorted and loaded in exosomes during their biogenesis. In this review we will discuss the current knowledge regarding the role invested by microRNAs, a family of short non-coding RNAs frequently deregulated in malignancies and present in exosomes, in shaping the microenvironment in a cancer-dependent manner.

  9. Reimmunization after bone marrow transplantation: Current recommendations and perspectives

    Directory of Open Access Journals (Sweden)

    Machado Clarisse M.

    2002-01-01

    Full Text Available Autologous and allogeneic BMT recipients lose immune memory of exposition to infectious agents and vaccines accumulated throughout lifetime and therefore need to be revaccinated. Diphtheria toxoid, tetanus toxoid, pertussis vaccine (children < 7 years old, Haemophilus influenza type B (Hib conjugate, 23-valent pneumococcal polysaccharide, inactivated influenza vaccine, inactivated polio vaccine and live-attenuated measles-mumps-rubella vaccine are the currently recommended vaccines to be included in a vaccination program after BMT. For most of them, the best time of vaccination, the number of vaccine doses and/or the duration of immunity after vaccination have not been established. Vaccination protocols vary greatly among BMT centers suggesting that the lack of sufficient data has not permitted the establishment of solid recommendations. The use of other vaccines and the perspectives for different vaccination protocols are discussed in this review.

  10. Molecular Testing of Lymphoproliferative Disorders: Current Status and Perspectives

    Directory of Open Access Journals (Sweden)

    Yoon Kyung Jeon

    2017-05-01

    Full Text Available Molecular pathologic testing plays an important role for the diagnosis, prognostication and decision of treatment strategy in lymphoproliferative disease. Here, we briefly review the molecular tests currently used for lymphoproliferative disease and those which will be implicated in clinical practice in the near future. Specifically, this guideline addresses the clonality test for B- and T-cell proliferative lesions, molecular cytogenetic tests for malignant lymphoma, determination of cell-of-origin in diffuse large B-cell lymphoma, and molecular genetic alterations incorporated in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Finally, a new perspective on the next-generation sequencing for diagnostic, prognostic, and therapeutic purpose in malignant lymphoma will be summarized.

  11. Molecular Testing of Lymphoproliferative Disorders: Current Status and Perspectives.

    Science.gov (United States)

    Jeon, Yoon Kyung; Yoon, Sun Och; Paik, Jin Ho; Kim, Young A; Shin, Bong Kyung; Kim, Hyun-Jung; Cha, Hee Jeong; Kim, Ji Eun; Huh, Jooryung; Ko, Young-Hyeh

    2017-05-01

    Molecular pathologic testing plays an important role for the diagnosis, prognostication and decision of treatment strategy in lymphoproliferative disease. Here, we briefly review the molecular tests currently used for lymphoproliferative disease and those which will be implicated in clinical practice in the near future. Specifically, this guideline addresses the clonality test for B- and T-cell proliferative lesions, molecular cytogenetic tests for malignant lymphoma, determination of cell-of-origin in diffuse large B-cell lymphoma, and molecular genetic alterations incorporated in the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Finally, a new perspective on the next-generation sequencing for diagnostic, prognostic, and therapeutic purpose in malignant lymphoma will be summarized.

  12. Current developments and future perspectives for TB diagnostics.

    Science.gov (United States)

    Palomino, Juan Carlos

    2012-01-01

    TB persists as a global epidemic with high morbidity and mortality, especially in low-income countries. It is the only infectious disease ever declared as a global emergency by the WHO. The HIV pandemic and the emergence of drug resistance represent two additional obstacles to better control of the disease. Important progress has been made in the last decade in TB diagnostics. Major needs still exist, such as the availability of a real point-of-care test, a better diagnosis of TB in immune-compromised populations and in children, and the possibility to predict progression to disease in latently infected people. This review will summarize the current developments in TB diagnostics and the perspectives for future developments in the field.

  13. Food reward system: current perspectives and future research needs.

    Science.gov (United States)

    Alonso-Alonso, Miguel; Woods, Stephen C; Pelchat, Marcia; Grigson, Patricia Sue; Stice, Eric; Farooqi, Sadaf; Khoo, Chor San; Mattes, Richard D; Beauchamp, Gary K

    2015-05-01

    This article reviews current research and cross-disciplinary perspectives on the neuroscience of food reward in animals and humans, examines the scientific hypothesis of food addiction, discusses methodological and terminology challenges, and identifies knowledge gaps and future research needs. Topics addressed herein include the role of reward and hedonic aspects in the regulation of food intake, neuroanatomy and neurobiology of the reward system in animals and humans, responsivity of the brain reward system to palatable foods and drugs, translation of craving versus addiction, and cognitive control of food reward. The content is based on a workshop held in 2013 by the North American Branch of the International Life Sciences Institute. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute.

  14. Current Status and Future Perspectives of the COBRA Experiment

    Directory of Open Access Journals (Sweden)

    J. Ebert

    2013-01-01

    Full Text Available The aim of the COBRA experiment is to prove the existence of neutrinoless double-beta-decay (0νββ-decay and to measure its half-life. For this purpose a detector array made of cadmium-zinc-telluride (CdZnTe semiconductor detectors is operated at the Gran Sasso Underground Laboratory (LNGS in Italy. This setup is used to investigate the experimental issues of operating CdZnTe detectors in low-background mode and to identify potential background components, whilst additional studies are proceeding in surface laboratories. The experiment currently consists of monolithic, calorimetric detectors of coplanar grid design (CPG detectors. These detectors are 1 × 1 × 1 cm3 and are arranged in 4 × 4 detector layers. Ultimately four layers will be installed by the end of 2013, of which two are currently operating. To date 82.3 kg·days of data have been collected. In the region of interest for 116Cd around 2.8 MeV, the median energy resolution is 1.5% FWHM, and a background level near 1 counts/keV/kg/y has been reached. This paper gives an overview of the current status of the experiment and future perspectives.

  15. A Refined Bead-Free Method to Identify Astrocytic Exosomes in Primary Glial Cultures and Blood Plasma

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    Cory M. Willis

    2017-06-01

    Full Text Available Astrocytes are the most abundant glial cell type in the central nervous system (CNS and are known to fulfill critical homeostatic functions. Dysfunction of activated astrocytes is also known to participate in the development of several neurological diseases. Astrocytes can be uniquely identified by expression of the intermediate filament protein glial acidic fibrillary protein (GFAP. Herein, we report on the development of a rigorous and sensitive methodology to identify GFAP+ exosomes in primary culture using flow cytometry. We then demonstrate that activated astrocytes release increased amounts of exosomes in response to treatment with interleukin-1β. Using this methodology, we report the identification of GFAP+ exosomes in blood and then use a mouse model of inflammatory demyelination, experimental autoimmune encephalomyelitis (EAE, to examine whether the abundance of GFAP+ exosomes in blood circulation changes during clinical illness. We find a detectable increase in the presence of GFAP+ exosomes in EAE mice when compared with non-EAE, control mice. Our data provide a novel perspective on the presence of GFAP in blood as it identifies exosomes as potential astrocyte-derived signals within blood. These data are complementary to previous clinical studies that reported elevated GFAP protein in blood samples from multiple sclerosis (MS patients during a clinical relapse. These data also reveal the existence of a potential systemic role for astrocyte-derived exosomes in CNS conditions involving inflammation such as multiple sclerosis.

  16. Prospects for exosomes in immunotherapy of cancer

    OpenAIRE

    Mignot, G; Roux, S; Thery, Clotilde; S?gura, Elodie; Zitvogel, L

    2007-01-01

    Exosomes are nanometer sized membrane vesicles invaginating from multivesicular bodies and secreted from epithelial and hematopoietic cells. They were first described ?in vitro? but vesicles with the hallmarks of exosomes are present in vivo in germinal centers and biological fluids. Their protein and lipid composition are unique and could account for their expanding functions such as eradication of obsolete proteins, antigen presentation or ?Trojan horses? for viruses or prions. Exosome secr...

  17. Stem cell-transplantation therapy for adrenoleukodystrophy: current perspectives

    Directory of Open Access Journals (Sweden)

    Miller W

    2017-01-01

    Full Text Available Weston Miller Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA Abstract: Adrenoleukodystrophy (ALD is a rare, X-linked peroxisomal disorder of impaired very long-chain fatty-acid metabolism. It results from various mutations in the ABCD1 gene (Xq28. All males with the biochemical defect of ALD are at risk of developing cerebral white-matter disease (cALD during their lifetime. Thirty-five percent of ALD patients develop cALD in boyhood, a life-threatening phenotype characterized by rapidly expanding, neuroinflammatory demyelination and irreversible clinical neurologic decline. The ABCD1 genotype does not predict susceptibility to or protection from the childhood cALD phenotype; therefore, clinicians must remain ever vigilant for its development when monitoring ALD patients. Currently, allogeneic hematopoietic cell transplantation (HCT is the standard of care for boyhood cALD. While HCT provides dramatic functional survival benefit in boys with early, presymptomatic cALD, outcomes are less favorable and less predictable for those with more advanced disease. Furthermore, little is known about how successful HCT in childhood might impact the onset of central nervous system disease in adulthood. Finally, investigations of experimental gene-therapy strategies are ongoing. This review explores current perspectives of stem cell transplantation in cALD. Keywords: adrenoleukodystrophy, cerebral adrenoleukodystrophy, stem cell transplantation, bone marrow transplantation, umbilical cord-blood transplantation, hematopoietic cell transplantation 

  18. Robotic general surgery: current practice, evidence, and perspective.

    Science.gov (United States)

    Jung, M; Morel, P; Buehler, L; Buchs, N C; Hagen, M E

    2015-04-01

    Robotic technology commenced to be adopted for the field of general surgery in the 1990s. Since then, the da Vinci surgical system (Intuitive Surgical Inc, Sunnyvale, CA, USA) has remained by far the most commonly used system in this domain. The da Vinci surgical system is a master-slave machine that offers three-dimensional vision, articulated instruments with seven degrees of freedom, and additional software features such as motion scaling and tremor filtration. The specific design allows hand-eye alignment with intuitive control of the minimally invasive instruments. As such, robotic surgery appears technologically superior when compared with laparoscopy by overcoming some of the technical limitations that are imposed on the surgeon by the conventional approach. This article reviews the current literature and the perspective of robotic general surgery. While robotics has been applied to a wide range of general surgery procedures, its precise role in this field remains a subject of further research. Until now, only limited clinical evidence that could establish the use of robotics as the gold standard for procedures of general surgery has been created. While surgical robotics is still in its infancy with multiple novel systems currently under development and clinical trials in progress, the opportunities for this technology appear endless, and robotics should have a lasting impact to the field of general surgery.

  19. Tumour exosome integrins determine organotropic metastasis.

    Science.gov (United States)

    Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Tesic Mark, Milica; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M; Dumont-Cole, Vanessa D; Kramer, Kimberly; Wexler, Leonard H; Narendran, Aru; Schwartz, Gary K; Healey, John H; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H; Grandgenett, Paul M; Hollingsworth, Michael A; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K; Jarnagin, William R; Brady, Mary S; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J; Bissell, Mina J; Garcia, Benjamin A; Kang, Yibin; Rajasekhar, Vinagolu K; Ghajar, Cyrus M; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

    2015-11-19

    Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

  20. Tumour exosome integrins determine organotropic metastasis

    Science.gov (United States)

    Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Mark, Milica Tesic; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E.; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M.; Dumont-Cole, Vanessa D.; Kramer, Kimberly; Wexler, Leonard H.; Narendran, Aru; Schwartz, Gary K.; Healey, John H.; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H.; Grandgenett, Paul M.; Hollingsworth, Michael A.; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K.; Jarnagin, William R.; Brady, Mary S.; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J.; Bissell, Mina J.; Garcia, Benjamin A.; Kang, Yibin; Rajasekhar, Vinagolu K.; Ghajar, Cyrus M.; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

    2015-01-01

    Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis. PMID:26524530

  1. Novel Modulators of Asthma and Allergy: Exosomes and MicroRNAs

    Directory of Open Access Journals (Sweden)

    Beatriz Sastre

    2017-07-01

    Full Text Available Intercellular communication is crucial to the immune system response. In the recent years, the discovery of exosomes has changed the way immune response orchestration was understood. Exosomes are able to operate as independent units that act as mediators in both physiological and pathological conditions. These structures contain proteins, lipidic mediators, and nucleic acids and notoriously include microRNAs (miRNAs. miRNAs are short RNA sequences (around 19–22 nucleotides with a high phylogenetic conservation and can partially or totally regulate multiple mRNAs, inhibiting protein synthesis. In respiratory diseases such as asthma and allergic sensitization, exosomes released by several cell types and their specific content perform crucial functions in the development and continuation of the pathogenic mechanisms. Released exosomes and miRNAs inside them have been found in different types of clinical samples, such as bronchoalveolar lavage fluids and sputum supernatants, providing new data about the environmental factors and mediators that participate in the inflammatory responses that lead to the exacerbation of asthma. In this review, we summarize our current knowledge of the role of exosomes and miRNAs in asthma and allergic sensitization, paying attention to the functions that both exosomes and miRNAs are described to perform through the literature. We review the effect of exosomes and miRNAs in cells implicated in asthma pathology and the genes and pathways that they modify in them, depicting how their behavior is altered in disease status. We also describe their possible repercussion in asthma diagnosis through their possible role as biomarkers. Therefore, both exosomes and miRNAs can be viewed as potential tools to be added to the arsenal of therapeutics to treat this disease.

  2. Effects of embryo-derived exosomes on the development of bovine cloned embryos.

    Science.gov (United States)

    Qu, Pengxiang; Qing, Suzhu; Liu, Ruiqi; Qin, Hongyu; Wang, Weiwei; Qiao, Fang; Ge, Hui; Liu, Jun; Zhang, Yong; Cui, Wei; Wang, Yongsheng

    2017-01-01

    The developmental competence of in vitro cultured (IVC) embryos is markedly lower than that of their in vivo counterparts, suggesting the need for optimization of IVC protocols. Embryo culture medium is routinely replaced three days after initial culture in bovine, however, whether this protocol is superior to continuous nonrenewal culture method under current conditions remains unclear. Using bovine somatic cell nuclear transfer (SCNT) embryos as the model, our results showed that compared with routine renewal treatment, nonrenewal culture system significantly improved blastocyst formation, blastocyst quality (increased total cell number, decreased stress and apoptosis, enhanced Oct-4 expression and ratio of ICM/TE), as well as following development to term. Existence and function of SCNT embryo-derived exosomes were then investigated to reveal the cause of impaired development induced by culture medium replacement. Exosomes were successfully isolated through differential centrifugation and identified by both electron microscopy and immunostaining against exosomal membrane marker CD9. Supplementation of extracted exosomes into freshly renewed medium significantly rescued not only blastocyst formation and quality (in vitro development), but also following growth to term (in vivo development). Notably, ratio of ICM/TE and calving rate were enhanced to a similar level as that in nonrenewal group. In conclusion, our results for the first time indicate that 1: bovine SCNT embryos can secrete exosomes into chemically defined culture medium during IVC; 2: secreted exosomes are essential for SCNT blastocyst formation, blastocyst quality, and following development to term; 3: removal of exosomes induced by culture medium replacement impairs SCNT embryo development, which can be avoided by nonrenewal culture procedure or markedly recovered by exosome supplementation.

  3. Cancer becomes wasteful: emerging roles of exosomes in cell-fate determination

    Directory of Open Access Journals (Sweden)

    Franz Wendler

    2013-09-01

    Full Text Available Extracellular vesicles (EVs, including exosomes, have been widely recognized for their role in intercellular communication of the immune response system. In the past few years, significance has been given to exosomes in the induction and modulation of cell-fate-inducing signalling pathways, such as the Hedgehog (Hh, Wnts, Notch, transforming growth factor (TGF-β, epidermal growth factor (EGF and fibroblast growth factor (FGF pathways, placing them in the wider context of development and also of cancer. These protein families induce signalling cascades responsible for tissue specification, homeostasis and maintenance. Exosomes contribute to cell-fate signal secretion, and vice versa exosome secretion can be induced by these proteins. Interestingly, exosomes can also transfer their mRNA to host cells or modulate the signalling pathways directly by the removal of downstream effector molecules from the cell. Surprisingly, much of what we know about the function of exosomes in cell determination is gathered from pathological transformed cancer cells and wound healing while data about their biogenesis and biology in normal developing and adult tissue lag behind. In this report, we will summarize some of the published literature and point to current advances and questions in this fast-developing topic. In a brief foray, we will also update and shortly discuss their potential in diagnosis and targeted cancer treatment.

  4. Quantifying exosome secretion from single cells reveals a modulatory role for GPCR signaling.

    Science.gov (United States)

    Verweij, Frederik Johannes; Bebelman, Maarten P; Jimenez, Connie R; Garcia-Vallejo, Juan J; Janssen, Hans; Neefjes, Jacques; Knol, Jaco C; de Goeij-de Haas, Richard; Piersma, Sander R; Baglio, S Rubina; Verhage, Matthijs; Middeldorp, Jaap M; Zomer, Anoek; van Rheenen, Jacco; Coppolino, Marc G; Hurbain, Ilse; Raposo, Graça; Smit, Martine J; Toonen, Ruud F G; van Niel, Guillaume; Pegtel, D Michiel

    2018-01-16

    Exosomes are small endosome-derived extracellular vesicles implicated in cell-cell communication and are secreted by living cells when multivesicular bodies (MVBs) fuse with the plasma membrane (PM). Current techniques to study exosome physiology are based on isolation procedures after secretion, precluding direct and dynamic insight into the mechanics of exosome biogenesis and the regulation of their release. In this study, we propose real-time visualization of MVB-PM fusion to overcome these limitations. We designed tetraspanin-based pH-sensitive optical reporters that detect MVB-PM fusion using live total internal reflection fluorescence and dynamic correlative light-electron microscopy. Quantitative analysis demonstrates that MVB-PM fusion frequency is reduced by depleting the target membrane SNAREs SNAP23 and syntaxin-4 but also can be induced in single cells by stimulation of the histamine H1 receptor (H1HR). Interestingly, activation of H1R1 in HeLa cells increases Ser110 phosphorylation of SNAP23, promoting MVB-PM fusion and the release of CD63-enriched exosomes. Using this single-cell resolution approach, we highlight the modulatory dynamics of MVB exocytosis that will help to increase our understanding of exosome physiology and identify druggable targets in exosome-associated pathologies. © 2018 Verweij et al.

  5. Predicting and managing sepsis in burn patients: current perspectives

    Directory of Open Access Journals (Sweden)

    Nunez Lopez O

    2017-08-01

    Full Text Available Omar Nunez Lopez,1,2 Janos Cambiaso-Daniel,1–3 Ludwik K Branski,1,2 William B Norbury,1,2 David N Herndon1,2,4 1Department of Surgery, University of Texas Medical Branch, 2Shriners Hospitals for Children, Galveston, TX, USA; 3Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Graz, Austria; 4Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA Abstract: Modern burn care has led to unprecedented survival rates in burn patients whose injuries were fatal a few decades ago. Along with improved survival, new challenges have emerged in the management of burn patients. Infections top the list of the most common complication after burns, and sepsis is the leading cause of death in both adult and pediatric burn patients. The diagnosis and management of sepsis in burns is complex as a tremendous hypermetabolic response secondary to burn injury can be superimposed on systemic infection, leading to organ dysfunction. The management of a septic burn patient represents a challenging scenario that is commonly encountered by providers caring for burn patients despite preventive efforts. Here, we discuss the current perspectives in the diagnosis and treatment of sepsis and septic shock in burn patients. Keywords: burn injury, thermal injury, burn sepsis, procalcitonin, antibiotics, biomarkers, cytokines

  6. Treatment of preeclampsia: current approach and future perspectives.

    Science.gov (United States)

    Berzan, Ecaterina; Doyle, Ross; Brown, Catherine M

    2014-09-01

    Hypertension is the most common medical disorder encountered during pregnancy, occurring in about 6-8 % of pregnancies. Preeclampsia is a pregnancy-specific disorder that occurs after 20 weeks' gestation, characterized by hypertension and proteinuria. Preeclampsia can also occur superimposed upon chronic hypertension. Eclampsia is the convulsive form of preeclampsia, and affects 0.1 % of all pregnancies. In low-income and middle-income countries, preeclampsia and eclampsia are associated with 10-15 % of direct maternal deaths. Women who develop preeclampsia in pregnancy are at greater risk of cardiovascular and cerebrovascular events even years after their pregnancies. There is significant progress in the elucidation of the underlying mechanisms and pathophysiology of preeclampsia, although its therapeutics remains challenging; delivery of the fetus is still the definitive treatment. Different international societies have produced recommendations and guidelines for clinicians treating preeclampsia, with an overall goal of improving maternal and fetal outcomes. In this review, we focus on the level of blood pressure at which to commence treatment and the current clinical management strategies available to treat and possibly prevent preeclampsia. We also briefly outline some newer perspectives on management of the disorder.

  7. Medicinal mushroom science: Current perspectives, advances, evidences, and challenges.

    Science.gov (United States)

    Wasser, Solomon P

    2014-01-01

    The main target of the present review is to draw attention to the current perspectives, advances, evidences, challenges, and future development of medicinal mushroom science in the 21 st century. Medicinal mushrooms and fungi are thought to possess approximately 130 medicinal functions, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, anti-hypercholesterolemic, antiviral, antibacterial, anti-parasitic, antifungal, detoxification, hepatoprotective, and antidiabetic effects. Many, if not all, higher Basidiomycetes mushrooms contain biologically active compounds in fruit bodies, cultured mycelium, and cultured broth. Special attention is paid to mushroom polysaccharides. The data on mushroom polysaccharides and different secondary metabolites are summarized for approximately 700 species of higher hetero- and homobasidiomycetes. Numerous bioactive polysaccharides or polysaccharide-protein complexes from the medicinal mushrooms described appear to enhance innate and cell-mediated immune responses, and exhibit antitumor activities in animals and humans. Whilst the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom compounds appear central. Polysaccharides and low-molecular-weight secondary metabolites are particularly important due to their antitumor and immunostimulating properties. Several of the mushroom compounds have been subjected to Phase I, II, and III clinical trials, and are used extensively and successfully in Asia to treat various cancers and other diseases. Special attention is given to many important unsolved problems in the study of medicinal mushrooms.

  8. Management of Candida infections in liver transplant recipients: current perspectives

    Directory of Open Access Journals (Sweden)

    Lingegowda PB

    2014-07-01

    Full Text Available Pushpalatha B Lingegowda,1–3 Tan Ban Hock1,2,4,5 1Department of Infectious Diseases, Singapore General Hospital, 2DUKE-NUS Graduate Medical School, 3Yong Loo Lin School of Medicine, National University of Singapore, 4SingHealth Internal Medicine Residency Program, 5Faculty of Medicine, National University of Singapore, Singapore Abstract: Liver transplantation has emerged as a widely accepted lifesaving therapeutic option for many patients with a variety of liver diseases. Improved surgical and medical management has led to significant improvements in post-transplant survival rates with a 1 year and 5 year patient survival of 87% and 73%, respectively. A high mortality rate due to infections during the first post-transplant year persists. Invasive candidiasis is recognized as a significant problem associated with high morbidity and mortality. Recent surveillance data has helped to understand the changes in the epidemiology and the evolving trends in the use of antifungal agents for prophylaxis and treatment combined with the challenges of managing these invasive fungal infections, which has led the transplant community to explore the best management strategies. The emergence of resistant fungi and excess costs in managing these invasive fungal infections has added to the complexities of management. In this context, current perspectives in the management of Candida infections in liver transplant recipients will be reviewed. Keywords: Candida infections, management, liver transplant

  9. Computational Identification of Novel Genes: Current and Future Perspectives.

    Science.gov (United States)

    Klasberg, Steffen; Bitard-Feildel, Tristan; Mallet, Ludovic

    2016-01-01

    While it has long been thought that all genomic novelties are derived from the existing material, many genes lacking homology to known genes were found in recent genome projects. Some of these novel genes were proposed to have evolved de novo, ie, out of noncoding sequences, whereas some have been shown to follow a duplication and divergence process. Their discovery called for an extension of the historical hypotheses about gene origination. Besides the theoretical breakthrough, increasing evidence accumulated that novel genes play important roles in evolutionary processes, including adaptation and speciation events. Different techniques are available to identify genes and classify them as novel. Their classification as novel is usually based on their similarity to known genes, or lack thereof, detected by comparative genomics or against databases. Computational approaches are further prime methods that can be based on existing models or leveraging biological evidences from experiments. Identification of novel genes remains however a challenging task. With the constant software and technologies updates, no gold standard, and no available benchmark, evaluation and characterization of genomic novelty is a vibrant field. In this review, the classical and state-of-the-art tools for gene prediction are introduced. The current methods for novel gene detection are presented; the methodological strategies and their limits are discussed along with perspective approaches for further studies.

  10. Mechanisms and applications of plant growth promoting rhizobacteria: Current perspective

    Directory of Open Access Journals (Sweden)

    Munees Ahemad

    2014-01-01

    Full Text Available Plant growth promoting rhizobacteria are the soil bacteria inhabiting around/on the root surface and are directly or indirectly involved in promoting plant growth and development via production and secretion of various regulatory chemicals in the vicinity of rhizosphere. Generally, plant growth promoting rhizobacteria facilitate the plant growth directly by either assisting in resource acquisition (nitrogen, phosphorus and essential minerals or modulating plant hormone levels, or indirectly by decreasing the inhibitory effects of various pathogens on plant growth and development in the forms of biocontrol agents. Various studies have documented the increased health and productivity of different plant species by the application of plant growth promoting rhizobacteria under both normal and stressed conditions. The plant-beneficial rhizobacteria may decrease the global dependence on hazardous agricultural chemicals which destabilize the agro-ecosystems. This review accentuates the perception of the rhizosphere and plant growth promoting rhizobacteria under the current perspectives. Further, explicit outlooks on the different mechanisms of rhizobacteria mediated plant growth promotion have been described in detail with the recent development and research. Finally, the latest paradigms of applicability of these beneficial rhizobacteria in different agro-ecosystems have been presented comprehensively under both normal and stress conditions to highlight the recent trends with the aim to develop future insights.

  11. Hypertrophic cardiomyopathy in 2013: Current speculations and future perspectives

    Science.gov (United States)

    Efthimiadis, Georgios K; Pagourelias, Efstathios D; Gossios, Thomas; Zegkos, Thomas

    2014-01-01

    Hypertrophic cardiomyopathy (HCM), the most variable cardiac disease in terms of phenotypic presentation and clinical outcome, represents the most common inherited cardiomyopathic process with an autosomal dominant trait of inheritance. To date, more than 1400 mutations of myofilament proteins associated with the disease have been identified, most of them “private” ones. This striking allelic and locus heterogeneity of the disease certainly complicates the establishment of phenotype-genotype correlations. Additionally, topics pertaining to patients’ everyday lives, such as sudden cardiac death (SCD) risk stratification and prevention, along with disease prognosis, are grossly related to the genetic variation of HCM. This review incorporates contemporary research findings and addresses major aspects of HCM, including preclinical diagnosis, genetic analysis, left ventricular outflow tract obstruction and SCD. More specifically, the spectrum of genetic analysis, the selection of the best method for obstruction alleviation and the need for a unique and accurate factor for SCD risk stratification are only some of the controversial HCM issues discussed. Additionally, future perspectives concerning HCM and myocardial ischemia, as well as atrial fibrillation, are discussed. Rather than enumerating clinical studies and guidelines, challenging problems concerning the disease are critically appraised by this review, highlighting current speculations and recommending future directions. PMID:24575171

  12. Medicinal mushroom science: Current perspectives, advances, evidences, and challenges

    Directory of Open Access Journals (Sweden)

    Solomon P Wasser

    2014-12-01

    Full Text Available The main target of the present review is to draw attention to the current perspectives, advances, evidences, challenges, and future development of medicinal mushroom science in the 21 st century. Medicinal mushrooms and fungi are thought to possess approximately 130 medicinal functions, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, anti-hypercholesterolemic, antiviral, antibacterial, anti-parasitic, antifungal, detoxification, hepatoprotective, and antidiabetic effects. Many, if not all, higher Basidiomycetes mushrooms contain biologically active compounds in fruit bodies, cultured mycelium, and cultured broth. Special attention is paid to mushroom polysaccharides. The data on mushroom polysaccharides and different secondary metabolites are summarized for approximately 700 species of higher hetero- and homobasidiomycetes. Numerous bioactive polysaccharides or polysaccharide-protein complexes from the medicinal mushrooms described appear to enhance innate and cell-mediated immune responses, and exhibit antitumor activities in animals and humans. Whilst the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom compounds appear central. Polysaccharides and low-molecular-weight secondary metabolites are particularly important due to their antitumor and immunostimulating properties. Several of the mushroom compounds have been subjected to Phase I, II, and III clinical trials, and are used extensively and successfully in Asia to treat various cancers and other diseases. Special attention is given to many important unsolved problems in the study of medicinal mushrooms.

  13. A current perspective on medical informatics and health sciences librarianship.

    Science.gov (United States)

    Perry, Gerald J; Roderer, Nancy K; Assar, Soraya

    2005-04-01

    The article offers a current perspective on medical informatics and health sciences librarianship. The authors: (1) discuss how definitions of medical informatics have changed in relation to health sciences librarianship and the broader domain of information science; (2) compare the missions of health sciences librarianship and health sciences informatics, reviewing the characteristics of both disciplines; (3) propose a new definition of health sciences informatics; (4) consider the research agendas of both disciplines and the possibility that they have merged; and (5) conclude with some comments about actions and roles for health sciences librarians to flourish in the biomedical information environment of today and tomorrow. Boundaries are disappearing between the sources and types of and uses for health information managed by informaticians and librarians. Definitions of the professional domains of each have been impacted by these changes in information. Evolving definitions reflect the increasingly overlapping research agendas of both disciplines. Professionals in these disciplines are increasingly functioning collaboratively as "boundary spanners," incorporating human factors that unite technology with health care delivery.

  14. The role of exosomes in peripheral nerve regeneration

    Directory of Open Access Journals (Sweden)

    Rosanna C Ching

    2015-01-01

    Full Text Available Peripheral nerve injuries remain problematic to treat, with poor functional recovery commonly observed. Injuries resulting in a nerve gap create specific difficulties for axonal regeneration. Approaches to address these difficulties include autologous nerve grafts (which are currently the gold standard treatment and synthetic conduits, with the latter option being able to be impregnated with Schwann cells or stem cells which provide an appropriate micro-environment for neuronal regeneration to occur. Transplanting stem cells, however, infers additional risk of malignant transformation as well as manufacturing difficulties and ethical concerns, and the use of autologous nerve grafts and Schwann cells requires the sacrifice of a functioning nerve. A new approach utilizing exosomes, secreted extracellular vesicles, could avoid these complications. In this review, we summarize the current literature on exosomes, and suggest how they could help to improve axonal regeneration following peripheral nerve injury.

  15. SaudiVeg ecoinformatics: Aims, current status and perspectives

    Directory of Open Access Journals (Sweden)

    Mohamed A. El-Sheikh

    2017-02-01

    Full Text Available During the last decade many electronic databases of vegetation plots were established in many countries around the world. These databases contain valuable phytosociological information assisting both governmental and NGO (Non-governmental organizations agencies to formulate strategies and on-ground plans to manage and protect nature resources. This paper provides an account on aims, current status and perspectives of building of a vegetation database for the Central Region (Najd of Saudi Arabia – the founding element of the Saudi Vegetation Database (SVD. The data stored by the database are sample plots (vegetation relevés collected according to the field techniques of the Braun-Blanquet approach (lists of taxa accompanied by semi-quantitative cover assessment, and are accompanied by general vegetation characteristics such as vegetation layering and cover, information on life-form of the recorded species, geographical coordinates, altitude, soil typology, topography and many more. More than 2900 vegetation-plot records (relevés have so far been collected in the Najd region; of these more than 2000 have already been stored using the Turboveg database platform. These field records cover many habitats such as depressions, wadis (dry river beds, agricultural lands, sand dunes, sabkhas, and ruderal habitats. The ecological information collected in the database is currently the largest set of vegetation data collated into a database in the Middle East. These data are of great importance for biodiversity studies in Saudi Arabia, since the region is recording a loss of biodiversity at a fast rate due to environmental problems such as global warming and land-use changes. We envisage that this database would catalyze further data collection on vegetation of the entire Arabian Peninsula, and shall serve as one of the most important datasets for classification and mapping of the vegetation of the Kingdom of Saudi Arabia.

  16. Biochemistry and Function of the RNA Exosomes

    DEFF Research Database (Denmark)

    Lubas, Michal Szymon; Chlebowski, Aleksander; Dziembowski, Andrzej

    2012-01-01

    Discovery of the evolutionary conserved RNA exosome was a milestone in RNA biology. First identified as an activity essential for the processing of ribosomal RNA, the exosome has since proved to be central for RNA processing and degradation in both the nucleus and the cytoplasm of eukaryotic cell...

  17. Traditional medicines and globalization: current and future perspectives in ethnopharmacology

    Directory of Open Access Journals (Sweden)

    Marco eLeonti

    2013-07-01

    Full Text Available The ethnopharmacological approach towards the understanding and appraisal of traditional and herbal medicines is characterized by the inclusions of the social as well as the natural sciences. Anthropological field-observations describing the local use of nature-derived medicines are the basis for ethnopharmacological enquiries. The multidisciplinary scientific validation of indigenous drugs is of relevance to modern societies at large and helps to sustain local health care practices. Especially with respect to therapies related to ageing related, chronic and infectious diseases traditional medicines offer promising alternatives to biomedicine. Bioassays applied in ethnopharmacology represent the molecular characteristics and complexities of the disease or symptoms for which an indigenous drug is used in traditional medicine to variable depth and extent. One-dimensional in vitro approaches rarely cope with the complexity of human diseases and ignore the concept of polypharmacological synergies. The recent focus on holistic approaches and systems biology in medicinal plant research represents the trend towards the description and the understanding of complex multi-parameter systems.Ethnopharmacopoeias are non-static cultural constructs shaped by belief and knowledge systems. Intensified globalization and economic liberalism currently accelerates the interchange between local and global pharmacopoeias via international trade, television, the World Wide Web and print media. The increased infiltration of newly generated biomedical knowledge and introduction of foreign medicines into local pharmacopoeias leads to syncretic developments and generates a feedback loop. While modern and post-modern cultures and knowledge systems adapt and transform the global impact, they become more relevant for ethnopharmacology. Moreover, what is traditional, alternative or complementary medicine depends on the adopted historic-cultural perspective.

  18. Novel trends in affinity biosensors: current challenges and perspectives

    Science.gov (United States)

    Arugula, Mary A.; Simonian, Aleksandr

    2014-03-01

    Molecular biorecognition processes facilitate physical and biochemical interactions between molecules in all crucial metabolic pathways. Perhaps the target analyte and the biorecognition element interactions have the most impactful use in biosensing applications. Traditional analytical sensing systems offer excellent biorecognition elements with the ability to detect and determine the presence of analytes. High affinity antibodies and DNA play an important role in the development of affinity biosensors based on electrochemical, optical and mass sensitive approaches. Advancements in this area routinely employ labels, label free, nanoparticles, multifunctional matrices, carbon nanotubes and other methods to meet the requirements of its own application. However, despite increasing affinity ceilings for conventional biosensors, the field draws back in meeting specifically important demands, such as long-term stability, ultrasensitivity, rapid detection, extreme selectivity, strong biological base, calibration, in vivo measurements, regeneration, satisfactory performance and ease of production. Nevertheless, recent efforts through this line have produced novel high-tech nanosensing systems such as ‘aptamers’ and ‘phages’ which exhibit high-throughput sensing. Aptamers and phages are powerful tools that excel over antibodies in sensibility, stability, multi-detection, in vivo measurements and regeneration. Phages are superior in stability, screening for affinity-based target molecules ranging from small to proteins and even cells, and easy production. In this review, we focus mainly on recent developments in affinity-based biosensors such as immunosensors, DNA sensors, emphasizing aptasensors and phage-based biosensors basing on novel electrochemical, optical and mass sensitive detection techniques. We also address enzyme inhibition-based biosensors and the current problems associated with the above sensors and their future perspectives.

  19. Traditional medicines and globalization: current and future perspectives in ethnopharmacology.

    Science.gov (United States)

    Leonti, Marco; Casu, Laura

    2013-01-01

    The ethnopharmacological approach toward the understanding and appraisal of traditional and herbal medicines is characterized by the inclusions of the social as well as the natural sciences. Anthropological field-observations describing the local use of nature-derived medicines are the basis for ethnopharmacological enquiries. The multidisciplinary scientific validation of indigenous drugs is of relevance to modern societies at large and helps to sustain local health care practices. Especially with respect to therapies related to aging related, chronic and infectious diseases traditional medicines offer promising alternatives to biomedicine. Bioassays applied in ethnopharmacology represent the molecular characteristics and complexities of the disease or symptoms for which an indigenous drug is used in "traditional" medicine to variable depth and extent. One-dimensional in vitro approaches rarely cope with the complexity of human diseases and ignore the concept of polypharmacological synergies. The recent focus on holistic approaches and systems biology in medicinal plant research represents the trend toward the description and the understanding of complex multi-parameter systems. Ethnopharmacopoeias are non-static cultural constructs shaped by belief and knowledge systems. Intensified globalization and economic liberalism currently accelerates the interchange between local and global pharmacopoeias via international trade, television, the World Wide Web and print media. The increased infiltration of newly generated biomedical knowledge and introduction of "foreign" medicines into local pharmacopoeias leads to syncretic developments and generates a feedback loop. While modern and post-modern cultures and knowledge systems adapt and transform the global impact, they become more relevant for ethnopharmacology. Moreover, what is traditional, alternative or complementary medicine depends on the adopted historic-cultural perspective.

  20. The biology and function of exosomes in cancer

    OpenAIRE

    Kalluri, Raghu

    2016-01-01

    Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40?150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathway...

  1. Cell to Cell Signalling via Exosomes Through esRNA

    OpenAIRE

    Lotvall, Jan; Valadi, Hadi

    2007-01-01

    Exosomes are small vesicles of endosomal origin that can be released by many different cells to the microenvironment. Exosomes have been shown to participate in the immune system, by mediating antigen presentation. We have recently shown the presence of both mRNA and microRNA in exosomes, specifically in exosomes derived from mast cells. This RNA can be transferred between one mast cell to another, most likely through fusion of the exosome to the recipient cell membrane. The delivered RNA is ...

  2. Tuberculosis and diabetes: current state and future perspectives.

    Science.gov (United States)

    Pizzol, Damiano; Di Gennaro, Francesco; Chhaganlal, Kajal D; Fabrizio, Claudia; Monno, Laura; Putoto, Giovanni; Saracino, Annalisa

    2016-06-01

    This review outlines the association between tuberculosis and diabetes, focusing on epidemiology, physiopathology, clinical aspects, diagnosis and treatment, and evaluates future perspectives, with particular attention to developing countries. © 2016 John Wiley & Sons Ltd.

  3. Exosomes expressing carbonic anhydrase 9 promote angiogenesis.

    Science.gov (United States)

    Horie, Kengo; Kawakami, Kyojiro; Fujita, Yasunori; Sugaya, Maki; Kameyama, Koji; Mizutani, Kosuke; Deguchi, Takashi; Ito, Masafumi

    2017-10-21

    Exosomes or microvesicles that are secreted from cells are considered to play important roles in tumor microenvironment. Carbonic anhydrase 9 (CA9), which is induced by hypoxia-inducible factor 1 (HIF1) in response to hypoxia, is overexpressed in many types of cancer including renal cell carcinoma (RCC). We examined the expression level of CA9 in several RCC cell lines and found that the basal level of CA9 was much higher in OSRC-2 cells than in Caki-1, KMRC-1 and 786-O cells. Consistent with the intracellular expression levels, CA9 was abundantly detected in exosomes isolated by ultracentrifugation from OSRC-2 cells. Density gradient centrifugation of OSRC-2 and 786-O exosomes confirmed the co-presence of CA9 with exosomal markers. Upon hypoxia and treatment with CoCl2, a hypoxia mimic agent, the CA9 level in exosomes was increased for all cell lines. In order to examine the effects of CA9 exosomes on angiogenesis, we generated stably transfected HEK293 cells expressing CA9. Immunocytochemical staining demonstrated the uptake of CA9 exosomes by human umbilical vein endothelial cells (HUVEC). In vitro angiogenesis assays using HUVEC revealed that CA9 exosomes promoted migration and tube formation. Lastly, MMP2 expression was increased by treatment with CA9 exosomes in HUVEC. Taken together, our results suggest the possibility that CA9 exosomes released from hypoxic RCC may enhance angiogenesis in microenvironment, thereby contributing to cancer progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Cell-specific uptake of mantle cell lymphoma-derived exosomes by malignant and non-malignant B-lymphocytes

    Science.gov (United States)

    Hazan-Halevy, Inbal; Rosenblum, Daniel; Weinstein, Shiri; Bairey, Osnat; Raanani, Pia; Peer, Dan

    2015-01-01

    Mantle cell lymphoma (MCL) is an aggressive and incurable mature B cell neoplasm. The current treatments are based on chemotherapeutics and new class of drugs (e.g. Ibrutinib®), which in most cases ends with tumor resistance and relapse. Therefore, further development of novel therapeutic modalities are needed. Exosomes are natural extracellular vesicles, which play an important role in intercellular communication. The specificity of exosome uptake by different target cells remains unknown. In this study, we observed that MCL exosomes are taken up rapidly and preferentially by MCL cells. Only minor fraction of exosomes was internalized into T-cell leukemia and bone marrow stroma cell lines, when these cells were co-cultured with MCL cells. Moreover, MCL patients’ exosomes were taken up by both healthy and patients’ B-lymphocytes with no apparent internalization to T lymphocytes and NK cells. Exosome internalization was not inhibited by specific siRNA against caveolin1 and clathrin but was found to be mediated by cholesterol-dependent pathway. These findings demonstrate natural specificity of exosomes to B-lymphocytes and ultimately might be used for therapeutic intervention in B cells malignancies. PMID:25933830

  5. Placental Exosomes as Early Biomarker of Preeclampsia: Potential Role of Exosomal MicroRNAs Across Gestation.

    Science.gov (United States)

    Salomon, Carlos; Guanzon, Dominic; Scholz-Romero, Katherin; Longo, Sherri; Correa, Paula; Illanes, Sebastian E; Rice, Gregory E

    2017-09-01

    There is a need to develop strategies for early prediction of patients who will develop preeclampsia (PE) to establish preventive strategies to reduce the prevalence and severity of the disease and their associated complications. The objective of this study was to investigate whether exosomes and their microRNA cargo present in maternal circulation can be used as early biomarker for PE. A retrospective stratified study design was used to quantify total exosomes and placenta-derived exosomes present in maternal plasma of normal (n = 32 per time point) and PE (n = 15 per time point) pregnancies. Exosomes present in maternal circulation were determined by nanoparticle tracking analysis. An Illumina TruSeq® Small RNA Library Prep Kit was used to construct a small RNA library from exosomal RNA obtained from plasma samples. In presymptomatic women, who subsequently developed PE, the concentration of total exosomes and placenta-derived exosomes in maternal plasma was significantly greater than those observed in controls, throughout pregnancy. The area under the receiver operating characteristic curves for total exosome and placenta-derived exosome concentrations were 0.745 ± 0.094 and 0.829 ± 0.077, respectively. In total, over 300 microRNAs were identified in exosomes across gestation, where hsa-miR-486-1-5p and hsa-miR-486-2-5p were identified as the candidate microRNAs. Although the role of exosomes during PE remains to be fully elucidated, we suggest that the concentration and content of exosomes may be of diagnostic utility for women at risk for developing PE.

  6. FINANCIAL MARKET OF AZERBAIJAN: CURRENT CONDITION AND FUTURE PERSPECTIVES

    Directory of Open Access Journals (Sweden)

    R. Guliyev

    2014-01-01

    Full Text Available This article discusses the economic model of Azerbaijan. Main components of the financial market are being analyzed: state budget, state oil fund, banking system, foreign debt and etc. This article assesses the impact of the global financial crisis on the national economy. Moreover, future development perspectives of the financial market and the economy are being examined as well.

  7. Exosomes: a potential key target in cardio-renal syndrome

    Directory of Open Access Journals (Sweden)

    Laura eGonzalez-Calero

    2014-10-01

    Full Text Available Exosomes have proven roles in regulating immune response, antigen presentation, RNA and protein transfer, and cell–cell (organ–organ interaction/signaling. These microvesicles can be considered a mechanism of non-classical secretion of proteins, and they represent a sub-proteome, thus assisting in the difficult task of biomarker discovery in a biological fluid as urine, plasma or serum. A potential role of exosomes in the cardio-renal syndrome is currently underexplored. Cardiovascular disease (CVD continues to be the leading cause of morbidity and mortality worldwide and, particularly, rates of cardiovascular events and death consistently increase as kidney function worsens. In other words, chronic kidney disease acts as a risk multiplier. Unfortunately, the relationship between markers of cardiovascular risk in kidney pathology often differs from that in the general population. Efforts in the search for novel action mechanisms simultaneously operating in both pathologies are thus of maximum interest.This article focuses to the role of exosomes in cardiovascular and renal diseases, in the search for novel key targets of interaction between heart and kidneys.

  8. Functions of Exosomes and Microbial Extracellular Vesicles in Allergy and Contact and Delayed-Type Hypersensitivity.

    Science.gov (United States)

    Nazimek, Katarzyna; Bryniarski, Krzysztof; Askenase, Philip W

    2016-01-01

    Extracellular vesicles, such as exosomes, are newly recognized intercellular conveyors of functional molecular mechanisms. Notably, they transfer RNAs and proteins between different cells that can then participate in the complex pathogenesis of allergic and related hypersensitivity responses and disease mechanisms, as described herein. This review highlights this important new appreciation of the in vivo participation of such extracellular vesicles in the interactions between allergy-mediating cells. We take into account paracrine epigenetic exchanges mediated by surrounding stromal cells and the endocrine receipt of exosomes from distant cells via the circulation. Exosomes are natural ancient nanoparticles of life. They are made by all cells and in some form by all species down to fungi and bacteria, and are present in all fluids. Besides a new focus on their role in the transmission of genetic regulation, exosome transfer of allergens was recently shown to induce allergic inflammation. Importantly, regulatory and tolerogenic exosomes can potently inhibit allergy and hypersensitivity responses, usually acting nonspecifically, but can also proceed in an antigen-specific manner due to the coating of the exosome surface with antibodies. Deep analysis of processes mediated by exosomes should result in the development of early diagnostic biomarkers, as well as allergen-specific, preventive and therapeutic strategies. These will likely significantly diminish the risks of current allergen-specific parenteral desensitization procedures, and of the use of systemic immunosuppressive drugs. Since extracellular vesicles are physiological, they can be fashioned for the specific delivery of therapeutic molecular instructions through easily tolerated, noninvasive routes, such as oral ingestion, nasal administration, and perhaps even inhalation. © 2016 S. Karger AG, Basel.

  9. Functions of Exosomes and Microbial Extracellular Vesicles in Allergy and Contact and Delayed-Type Hypersensitivity

    Science.gov (United States)

    Nazimek, Katarzyna; Bryniarski, Krzysztof; Askenase, Philip W.

    2016-01-01

    Extracellular vesicles, such as exosomes, are newly recognized intercellular conveyors of functional molecular mechanisms. Notably, they transfer RNAs and proteins between cells in general, that then can participate, as described herein, in the complex pathogenesis of allergic and related hypersensitivity responses and disease mechanisms. This review highlights this important new appreciation of the in vivo participation of such extracellular vesicles in the interactions between allergy-mediating cells, taking into account paracrine epigenetic exchanges mediated by surrounding stromal cells and the endocrine receipt of exosomes from distant cells via the circulation. Exosomes are natural ancient nanoparticles of life. They are made by all cells and in some form by all species down to fungi and bacteria, and are present in all fluids. Besides a new focus on their role in the transmission of genetic regulation, exosome transfer of allergens was recently shown to induce allergic inflammation. Importantly, regulatory and tolerogenic exosomes can potently inhibit allergy and hypersensitivity responses, usually acting non-specifically, but also can proceed in an antigen-specific manner due to coating of the exosome surface with antibodies. Deep analysis of processes mediated by exosomes should result in development of early diagnostic biomarkers, as well as allergen-specific, preventive and therapeutic strategies. These likely will significantly diminish the risks of current allergen specific parenteral desensitization procedures, and of the use of systemic immunosuppressive drugs. Since extracellular vesicles are physiological, they can be fashioned for specific delivery of therapeutic molecular instructions through easily tolerated, non-invasive routes, such as oral ingestion, nasal administration, and perhaps even inhalation. PMID:27820941

  10. Childhood and violence in advertising. A current perspective

    OpenAIRE

    Martínez, Inmaculada José; María Dolores PRIETO; Farfán, Juana

    2006-01-01

    This article considers the subject of childhood and violence contained in the advertising format, focusing especially on television advertising. The article analyses the violent and aggressive content of audiovisual texts looking at childhood from a broader perspective than has been used in research to date, in order to show the wide spectrum of involvement of children in advertising material. This new focus implies looking at the subject of childhood and media violence in televised advertisi...

  11. Transcranial direct current stimulation of the right temporoparietal junction impairs third-person perspective taking

    NARCIS (Netherlands)

    Elk, M. van; Duizer, M.; Sligte, I.G.; Schie, H.T. van

    2017-01-01

    Given the current debates about the precise functional role of the right temporoparietal junction (rTPJ) in egocentric and exocentric perspective taking, in the present study we manipulated activity in the rTPJ to investigate the effects on a spatial perspective-taking task. Participants engaged in

  12. Transcranial direct current stimulation of the right temporoparietal junction impairs third-person perspective taking

    NARCIS (Netherlands)

    van Elk, M.; Duizer, M.; Sligte, I.; van Schie, H.

    Given the current debates about the precise functional role of the right temporoparietal junction (rTPJ) in egocentric and exocentric perspective taking, in the present study we manipulated activity in the rTPJ to investigate the effects on a spatial perspective-taking task. Participants engaged in

  13. Current perspectives on the US FDA regulatory framework for intelligent drug-delivery systems.

    Science.gov (United States)

    Sapsford, Kim E; Lauritsen, Kristina; Tyner, Katherine M

    2012-12-01

    The US FDA is the US agency responsible for regulating intelligent drug-delivery systems (IDDS). IDDS can be classified as a device, drug, biologic or combination product. In this perspective, the current regulatory framework for IDDS and future perspectives on how the field is expected to evolve from a regulatory standpoint is discussed.

  14. Exosomes derived from mesenchymal non-small cell lung cancer cells promote chemoresistance.

    Science.gov (United States)

    Lobb, Richard J; van Amerongen, Rosa; Wiegmans, Adrian; Ham, Sunyoung; Larsen, Jill E; Möller, Andreas

    2017-08-01

    Non-small cell lung cancer (NSCLC) is the most common lung cancer type and the most common cause of mortality in lung cancer patients. NSCLC is often associated with resistance to chemotherapeutics and together with rapid metastatic spread, results in limited treatment options and poor patient survival. NSCLCs are heterogeneous, and consist of epithelial and mesenchymal NSCLC cells. Mesenchymal NSCLC cells are thought to be responsible for the chemoresistance phenotype, but if and how this phenotype can be transferred to other NSCLC cells is currently not known. We hypothesised that small extracellular vesicles, exosomes, secreted by mesenchymal NSCLC cells could potentially transfer the chemoresistance phenotype to surrounding epithelial NSCLC cells. To explore this possibility, we used a unique human bronchial epithelial cell (HBEC) model in which the parental cells were transformed from an epithelial to mesenchymal phenotype by introducing oncogenic alterations common in NSCLC. We found that exosomes derived from the oncogenically transformed, mesenchymal HBECs could transfer chemoresistance to the parental, epithelial HBECs and increase ZEB1 mRNA, a master EMT transcription factor, in the recipient cells. Additionally, we demonstrate that exosomes from mesenchymal, but not epithelial HBECs contain the ZEB1 mRNA, thereby providing a potential mechanism for the induction of a mesenchymal phenotype in recipient cells. Together, this work demonstrates for the first time that exosomes derived from mesenchymal, oncogenically transformed lung cells can transfer chemoresistance and mesenchymal phenotypes to recipient cells, likely via the transfer of ZEB1 mRNA in exosomes. © 2017 UICC.

  15. Exosomes: secreted vesicles and intercellular communications

    OpenAIRE

    Théry, Clotilde

    2011-01-01

    Exosomes are small membrane vesicles of endocytic origin secreted by most cell types, and are thought to play important roles in intercellular communications. Although exosomes were originally described in 1983, interest in these vesicles has really increased dramatically in the last 3 years, after the finding that they contain mRNA and microRNA. This discovery sparked renewed interest for the general field of membrane vesicles involved in intercellular communications, and research on these s...

  16. Exosomes in tumor microenvironment: novel transporters and biomarkers.

    Science.gov (United States)

    Wang, Zhen; Chen, Jun-Qiang; Liu, Jin-Lu; Tian, Lei

    2016-10-19

    Tumor microenvironment (TME) plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Exosome is an important part of TME. Exosomes are small vesicles formed in vesicular bodies with a diameter of 30-100 nm and a classic "cup" or "dish" morphology. They can contain microRNAs, mRNAs, DNA fragments and proteins, which are shuttled from a donor cell to recipient cells. Exosomes secreted from tumor cells are called tumor-derived (TD) exosomes. There is emerging evidence that TD exosomes can construct a fertile environment to support tumor proliferation, angiogenesis, invasion and premetastatic niche preparation. TD exosomes also may facilitate tumor growth and metastasis by inhibiting immune surveillance and by increasing chemoresistance via removal of chemotherapeutic drugs. Therefore, TD-exosomes might be potential targets for therapeutic interventions via their modification or removal. For example, exosomes can serve as specific delivery vehicles to tumors of drugs, small molecules, or agents of prevention and gene therapy. Furthermore, the biomarkers detected in exosomes of biological fluids imply a potential for exosomes in the early detection and diagnosis, prediction of therapeutic efficacy, and determining prognosis of cancer. Although exosomes may serve as cancer biomarkers and aid in the treatment of cancer, we have a long way to go before we can further enhance the anti-tumor therapy of exosomes and develop exosome-based cancer diagnostic and therapeutic strategies.

  17. How do new innovation paradigms challenge current innovation policy perspectives

    DEFF Research Database (Denmark)

    Knudsen, Mette Præst; Tanev, Stoyan; Bisgaard, Tanja

    2012-01-01

    Successful firms today are forced to deal with new competitive realities by being globally present, innovatively resourceful and internationally competitive on multiple markets across the world. The new competitive realities challenge firms to open their innovation processes by adopting new......-creation paradigm is relatively new, but with a significant potential to also affect formulation of new innovation policy perspectives. The three paradigms are considered as examples of distributive innovation, which is based on the need of firms to orchestrate and integrate the innovative contributions from...

  18. Transcranial direct current stimulation of the right temporoparietal junction impairs third-person perspective taking

    OpenAIRE

    van Elk, M; Duizer, M.; Sligte, I. G.; Schie, H.T. van

    2016-01-01

    Given the current debates about the precise functional role of the right temporoparietal junction (rTPJ) in egocentric and exocentric perspective taking, in the present study we manipulated activity in the rTPJ to investigate the effects on a spatial perspective-taking task. Participants engaged in a mental body transformation task, requiring them to mentally rotate their own body to the position of an avatar, while undergoing anodal, cathodal, or sham transcranial direct current stimulation ...

  19. Exploring the RNA landscape of endothelial exosomes.

    Science.gov (United States)

    Perez-Boza, Jennifer; Lion, Michelle; Struman, Ingrid

    2017-12-27

    Exosomes are small extracellular vesicles of around 100nm of diameter produced by most cell types. These vesicles carry nucleic acids, proteins, lipids and other biomolecules and function as carriers of biological information in processes of extracellular communication. The content of exosomes is regulated by the external and internal microenvironment of the parent cell, but the intrinsic mechanisms of loading of molecules into exosomes is still not completely elucidated. In this study, by the use of next generation sequencing we have characterized in depth the RNA composition of healthy endothelial cells and exosomes and provided an accurate profile of the different coding and non-coding RNA species found per compartment. We have also discovered a set of unique genes preferentially included (or excluded) into vesicles. Moreover, after studying the enrichment of RNA motifs in the genes unequally distributed between cells and exosomes, we have detected a set of enriched sequences for several classes of RNA. In conclusion, our results provide the basis to study the involvement of RNA-binding proteins capable to recognize RNA sequences and their role in the export of RNAs into exosomes. Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  20. More than Tiny Sacks: Stem Cell Exosomes as Cell-free Modality for Cardiac Repair

    Science.gov (United States)

    Kishore, Raj; Khan, Mohsin

    2015-01-01

    Stem cell therapy provides immense hope for regenerating the pathological heart yet has been marred by issues surrounding the effectiveness, unclear mechanisms and survival of the donated cell population in the ischemic myocardial milieu. Poor survival and engraftment coupled to inadequate cardiac commitment of the adoptively transferred stem cells compromises the improvement in cardiac function. Various alternative approaches to enhance the efficacy of stem cell therapies and to overcome issues with cell therapy have been employed with varied success. Cell free components such as exosomes enriched in proteins, mRNAs and miRs characteristic of parental stem cells represent a potential approach for treating cardiovascular diseases. Recently, exosomes from different kinds of stem cells have been effectively employed to promote cardiac function in the pathological heart. The aim of this review is to summarize current research efforts on stem cell exosomes including their potential benefits and limitations in order to develop a potentially viable therapy for cardiovascular problems. PMID:26838317

  1. The Use of Exosomes as Biomarkers for Evaluating and Monitoring Critically Ill Polytrauma Patients with Sepsis.

    Science.gov (United States)

    Ticlea, Marian; Bratu, Lavinia Melania; Bodog, Florian; Bedreag, Ovidiu Horea; Rogobete, Alexandru Florin; Crainiceanu, Zorin Petrisor

    2017-02-01

    Regarding genetic biomarkers for early assessment and monitoring the clinical course in polytrauma patients with sepsis, in recent years a remarkable evolution has been highlighted. One of the main representatives is the exosome miRNAs. In this paper, we would like to present in more details the various methods of using exosome miRNAs as a biomarker for monitoring polytrauma patients with sepsis, as well as establishing a belated outcome by aggregating the entire clinical aspects. The use of exosome miRNAs for late evaluating and monitoring the clinical evolution of polytrauma patients can bring significant improvements in current clinical practice through the optimization and modulation of intensive care according to the needs of each patient individually.

  2. Single dose treatment of malaria - current status and perspectives.

    Science.gov (United States)

    Mischlinger, Johannes; Agnandji, Selidji T; Ramharter, Michael

    2016-07-01

    Despite increased international efforts for control and ultimate elimination, malaria remains a major health problem. Currently, artemisinin-based combination therapies are the treatment of choice for uncomplicated malaria exhibiting high efficacy in clinical trial settings in sub-Saharan Africa. However, their administration over a three-day period is associated with important problems of treatment adherence resulting in markedly reduced effectiveness of currently recommended antimalarials under real world settings. Antimalarial drug candidates and antimalarial drug combinations currently under advanced clinical development for the indication as single dose antimalarial therapy. Expert commentary: Several new drug candidates and combinations are currently undergoing pivotal proof-of-concept studies or clinical development programmes. The development of a single dose combination therapy would constitute a breakthrough in the control of malaria. Such an innovative treatment approach would simultaneously close the effectiveness gap of current three-day therapies and revolutionize population based interventions in the context of malaria elimination campaigns.

  3. Exosomes: promising sacks for treating ischemic heart disease?

    Science.gov (United States)

    Chen, Gui-Hao; Xu, Jun; Yang, Yue-Jin

    2017-09-01

    Ischemic heart disease(IHD) is the leading cause of death worldwide. Despite the development of continuously improving therapeutic strategies, morbidity and mortality of patients with IHD remain relatively high. Exosomes are a subpopulation of vesicles that are universally recognized as major mediators in intercellular communication. Numerous preclinical studies have shown that these tiny vesicles were protective in IHD, through such actions as alleviating myocardial ischemia-reperfusion injury, promoting angiogenesis, inhibiting fibrosis, and facilitating cardiac regeneration. Our review focused on these beneficial exosome-mediated processes. In addition, we discuss in detail how to fully exploit the therapeutic potentials of exosomes in the field of IHD. Topics include identifying robust sources of exosomes, loading protective agents into exosomes, developing heart-specific exosomes, optimizing isolation methods, and translating the cardioprotective effects of exosomes into clinical practice. Finally, both the advantages and disadvantages of utilizing exosomes in clinical settings are addressed. Copyright © 2017 the American Physiological Society.

  4. Historical and current perspective on tobacco use and nicotine addiction.

    Science.gov (United States)

    Dani, John A; Balfour, David J K

    2011-07-01

    Although the addictive influence of tobacco was recognized very early, the modern concepts of nicotine addiction have relied on knowledge of cholinergic neurotransmission and nicotinic acetylcholine receptors (nAChRs). The discovery of the 'receptive substance' by Langley, that would turn out to be nAChRs, and 'Vagusstoff' (acetylcholine) by Loewi, coincided with an exciting time when the concept of chemical synaptic transmission was being formulated. More recently, the application of more powerful techniques and the study of animal models that replicate key features of nicotine dependence have led to important advancements in our understanding of molecular, cellular and systems mechanisms of nicotine addiction. In this review, we present a historical perspective and overview of the research that has led to our present understanding of nicotine addiction. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Hermeneutic phenomenology: philosophical perspectives and current use in nursing research.

    Science.gov (United States)

    Annells, M

    1996-04-01

    The wise choice of the postmodern tradition of hermeneutic phenomenology for nursing research is partly dependent upon an awareness of that tradition's base of philosophical hermeneutics. The origins of this philosophy within the work of Heidegger and especially Gadamer are detailed with an explanation of some major concepts intrinsic to their hermeneutic writings. Subsequently an analysis is offered of the ontological, epistemological and methodological perspectives of the tradition which is considered thereby to reside within an interpretivist/constructivist paradigm of inquiry. The contemporary use within the discipline of nursing of hermeneutic phenomenology is discussed, and the growing trend for using the tradition, across continents, is identified. However the question is posed as to whether all such research is accurately identified as belonging to the tradition. A further analysis suggests that hermeneutic phenomenology will increasingly be applied to the research of nursing phenomena.

  6. Biosorption: current perspectives on concept, definition and application.

    Science.gov (United States)

    Fomina, Marina; Gadd, Geoffrey Michael

    2014-05-01

    Biosorption is a physico-chemical and metabolically-independent process based on a variety of mechanisms including absorption, adsorption, ion exchange, surface complexation and precipitation. Biosorption processes are highly important in the environment and conventional biotreatment processes. As a branch of biotechnology, biosorption has been aimed at the removal or recovery of organic and inorganic substances from solution by biological material which can include living or dead microorganisms and their components, seaweeds, plant materials, industrial and agricultural wastes and natural residues. For decades biosorption has been heralded as a promising cost-effective clean-up biotechnology. Despite significant progress in our understanding of this complex phenomenon and a dramatic increase in publications in this research area, commercialization of biosorption technologies has been limited so far. This article summarizes existing knowledge on various aspects of the fundamentals and applications of biosorption and critically reviews the obstacles to commercial success and future perspectives. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Computer-assisted Orthopaedic Surgery: Current State and Future Perspective

    Directory of Open Access Journals (Sweden)

    Guoyan eZheng

    2015-12-01

    Full Text Available Introduced about two decades ago, computer-assisted orthopaedic surgery (CAOS has emerged as a new and independent area, due to the importance of treatment of musculoskeletal diseases in orthopaedics and traumatology, increasing availability of different imaging modalities, and advances in analytics and navigation tools. The aim of this paper is to present the basic elements of CAOS devices and to review state-of-the-art examples of different imaging modalities used to create the virtual representations, of different position tracking devices for navigation systems, of different surgical robots, of different methods for registration and referencing, and of CAOS modules that have been realized for different surgical procedures. Future perspectives will also be outlined.

  8. Clean Coal Technologies in China: Current Status and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Shiyan Chang

    2016-12-01

    Full Text Available Coal is the dominant primary energy source in China and the major source of greenhouse gases and air pollutants. To facilitate the use of coal in an environmentally satisfactory and economically viable way, clean coal technologies (CCTs are necessary. This paper presents a review of recent research and development of four kinds of CCTs: coal power generation; coal conversion; pollution control; and carbon capture, utilization, and storage. It also outlines future perspectives on directions for technology research and development (R&D. This review shows that China has made remarkable progress in the R&D of CCTs, and that a number of CCTs have now entered into the commercialization stage.

  9. DATA MINING IN EDUCATION: CURRENT STATE AND PERSPECTIVES OF DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Yurii O. Kovalchuk

    2016-01-01

    Full Text Available The main tasks (classification and regression, association rules, clustering and the basic principles of the Data Mining algorithms in the context of their use for a variety of research in the field of education which are the subject of a relatively new independent direction Educational Data Mining are considered. The findings about the most popular topics of research within this area as well as the perspectives of its development are presented. Presentation of the material is illustrated by simple examples. This article is intended for readers who are engaged in research in the field of education at various levels, especially those involved in the use of e-learning systems, but little familiar with this area of data analysis.

  10. Computer-Assisted Orthopedic Surgery: Current State and Future Perspective.

    Science.gov (United States)

    Zheng, Guoyan; Nolte, Lutz P

    2015-01-01

    Introduced about two decades ago, computer-assisted orthopedic surgery (CAOS) has emerged as a new and independent area, due to the importance of treatment of musculoskeletal diseases in orthopedics and traumatology, increasing availability of different imaging modalities, and advances in analytics and navigation tools. The aim of this paper is to present the basic elements of CAOS devices and to review state-of-the-art examples of different imaging modalities used to create the virtual representations, of different position tracking devices for navigation systems, of different surgical robots, of different methods for registration and referencing, and of CAOS modules that have been realized for different surgical procedures. Future perspectives will also be outlined.

  11. Proteomics, biomarkers, and HIV-1: A current perspective.

    Science.gov (United States)

    Donnelly, Maire Rose; Ciborowski, Pawel

    2016-02-01

    Despite more than three decades of extensive research, HIV-1 infection although well controlled with cART, remains incurable. Multifactorial complexity of the viral life-cycle poses great challenges in understanding molecular mechanisms underlying this infection and the development of biomarkers, which we hope will lead us to its eradication. For a more in-depth understanding of how the virus interacts with host target cells, T cells and macrophages, proteomic profiling techniques that offer strategies to investigate the proteome in its entirety were employed. Here, we review proteomic studies related to HIV-1 infection and discuss perspectives and limitations of proteomic and systems biology approaches in future studies. © 2015 The Authors. PROTEOMICS - Clinical Applications Published by WILEY-VCH Verlag GmbH & Co. KGaA.

  12. Risk definition and management strategies in retinoblastoma: current perspectives

    OpenAIRE

    Ghassemi, Fariba; Khodabande,Alireza

    2015-01-01

    Fariba Ghassemi, Alireza Khodabande Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Tehran Province, Islamic Republic of Iran Abstract: This manuscript focuses on high-risk factors of metastatic disease in retinoblastoma and evaluation of the current treatments of retinoblastoma. Presence of histopathologic high-risk factors is associated with a higher risk of local recurrence and systemic metastasis. Currently, globe-sparing therapies, including syste...

  13. Exosomes and autophagy: coordinated mechanisms for the maintenance of cellular fitness

    Directory of Open Access Journals (Sweden)

    Francesc eBaixauli

    2014-08-01

    Full Text Available Conditions resulting from loss of cellular homeostasis; including oxidative stress, inflammation, protein aggregation, endoplasmic reticulum stress, metabolic stress and perturbation of mitochondrial function, are common to many pathological disorders and contribute to aging. Cells face these stress situations by engaging quality control mechanisms aimed to restore cellular homeostasis and preserve cell viability. Among them, the autophagy-lysosome pathway mediates the specific degradation of damaged proteins and organelles, and its proper function is related to cellular protection and increased life span in many model organisms. Besides autophagy, increasing evidence underscores a role for exosomes in the selective secretion of harmful/damaged proteins and RNAs and thus, in the maintenance of cellular fitness. In this perspective article, we discuss the emerging function of exosomes as means of alleviating intracellular stress conditions, and how secretion of harmful or unwanted material in exosomes, in coordination with the autophagy-lysosomal pathway, is essential to preserve intracellular protein and RNA homeostasis. Finally, we provide an overview about the consequences of the spreading of the exosome content in physiological

  14. Micro RNA in Exosomes from HIV-Infected Macrophages.

    Science.gov (United States)

    Roth, William W; Huang, Ming Bo; Addae Konadu, Kateena; Powell, Michael D; Bond, Vincent C

    2015-12-22

    Exosomes are small membrane-bound vesicles secreted by cells that function to shuttle RNA and proteins between cells. To examine the role of exosomal micro RNA (miRNA) during the early stage of HIV-1 infection we characterized miRNA in exosomes from HIV-infected macrophages, compared with exosomes from non-infected macrophages. Primary human monocytes from uninfected donors were differentiated to macrophages (MDM) which were either mock-infected or infected with the macrophage-tropic HIV-1 BaL strain. Exosomes were recovered from culture media and separated from virus particles by centrifugation on iodixanol density gradients. The low molecular weight RNA fraction was prepared from purified exosomes. After pre-amplification, RNA was hybridized to microarrays containing probes for 1200 miRNA species of known and unknown function. We observed 48 miRNA species in both infected and uninfected MDM exosomes. Additionally, 38 miRNAs were present in infected-cell exosomes but not uninfected-cell exosomes. Of these, 13 miRNAs were upregulated in exosomes from HIV-infected cells, including 4 miRNA species that were increased by more than 10-fold. Though numerous miRNA species have been identified in HIV-infected cells, relatively little is known about miRNA content in exosomes from these cells. In the future, we plan to investigate whether the upregulated miRNA species we identified are increased in exosomes from HIV-1-positive patients.

  15. Exosomes: Some approaches to cancer diagnosis and therapy

    Science.gov (United States)

    Shtam, T.; Samsonov, R.; Kamyshinsky, R.; Pantina, R.; Verlov, N.; Vasiliev, A.; Konevega, A. L.; Malek, A. V.

    2017-09-01

    Exosomes are membrane-bound, intercellular communication shuttle vesicles that are defined by their endocytic origin and size range of 30-120 nm. Secreted by nearly all mammalian cell types and present in bodily fluids, exosomes confer messages between cells, by transporting functionally relevant proteins, nucleic acids, and lipids. The capability of tumor exosomes to house tumorigenic information and induce cellular responses that promote disease pathogenesis make tumor exosomes an attractive tool in identifying cancer biomarkers and exploiting exosomes for therapy. In this paper, we sum up our previous findings to utilize exosomes as biomarkers for early detection, diagnosis and therapy selection of prostate and thyroid cancer and present our results on exosomes in colon cancer. Some of plasma exosomal miRNAs showed their potential as diagnostic markers for colon cancer. All together, the data suggested the potentials of circulating exosomal miRNAs as liquid biopsy markers for cancer. Here we also present the possibilities of delivering therapeutic molecules by exosomes. Previously, we had demonstrated the potential of exosome-mediated siRNA delivery. Here, we present the possibility of carrying the exogenous p53 protein by exosomes in vitro.

  16. NON-TECHNOLOGICAL INNOVATION: CURRENT ISSUES AND PERSPECTIVES

    Directory of Open Access Journals (Sweden)

    Cristina Saraiva Pereira

    2013-06-01

    Full Text Available ABSTRACTInnovationcan be considered to be a complex phenomenon including technical andnon-technical aspects. A remarkable increase in the interdisciplinary attention devoted to innovation has been noticed over the recent decades but the formal technological and economic aspects of innovation have received much more attention and have been taken into account in a far greater number of analyses, despite the great importance of the non-technological dimension of innovation.This paper attempts a review on the important subject of non-technological innovation. The main ideas on the non-technological dimension of innovation research will be highlighted, followed by an attempt to integrate diverse and disparate perspectives on the subject, to present evidence on possible generalizations and to discuss eventual research gaps and opportunities for further studies. The relationship between technological and non-technological innovation is complex and not fully understood. Among several aspects that will be covered in this paper, two specific ones will receive special attention in this brief analysis: the evidence on the impacts of non-technological innovation, and the measurements efforts that have been made concerning this phenomenon.

  17. Current Challenges and Perspectives for Governing Forest Restoration

    Directory of Open Access Journals (Sweden)

    Manuel R. Guariguata

    2014-12-01

    Full Text Available Negotiation, reconciliation of multiple scales through both ecological and social dimensions and minimization of power imbalances are considered critical challenges to overcome for effective governance of forest restoration. Finding the right mix of “command and control” in forest restoration vs. “environmental governance”, which includes non-state actors, regulatory flexibility, and market based instruments is at the heart of these challenges. This Special Issue attempts at shedding light on these challenges with case studies from South and Central America, Africa, and Asia. Some provide within-country as well as cross-country comparisons. A few others present case studies at the household level. Both policy and legal constraints towards implementing forest restoration are also discussed as a function of top down vs. bottom up approaches. The effectiveness of payments for environmental services is examined as catalyzers of forest restoration initiatives. Finally, two papers deal with the legal and policy constraints in making restoration through natural regeneration a viable and cost-effective tool. In the face of renewed perspectives for expanding forest restoration programs globally, governance issues will likely play a key role in eventually determining success. As many of the papers in this Special Issue suggest, the fate of forest restoration outcomes is, more often than not, associated with overall governance challenges, some of which are often overlooked particularly across multiple scales.

  18. Fighting Sharka in Peach: Current Limitations and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Marco Cirilli

    2016-08-01

    Full Text Available Sharka, caused by Plum Pox Virus (PPV, is by far the most important infectious disease of peach [P. persica (L. Batsch] and other Prunus species. The progressive spread of the virus in many important growing areas throughout Europe poses serious issues to the economic sustainability of stone fruit crops, peach in particular. The adoption of internationally agreed-upon rules for diagnostic tests, strain-specific monitoring schemes and spatial-temporal modeling of virus spread, are all essential for a more effective sharka containment. The EU regulations on nursery activity should be modified based on the zone delimitation of PPV presence, limiting open-field production of propagation materials only to virus-free areas. Increasing the efficiency of preventive measures should be augmented by the short-term development of resistant cultivars. Putative sources of resistance/tolerance have been recently identified in peach germplasm, although the majority of novel resistant sources to PPV-M have been found in almond. However, the complexity of introgression from related-species imposes the search for alternative strategies. The use of genetic engineering, particularly RNAi-based approaches, appears as one of the most promising perspectives to introduce a durable resistance to PPV in peach germplasm, notwithstanding the well-known difficulties of in vitro plant regeneration in this species. In this regard, rootstock transformation to induce RNAi-mediated systemic resistance to PPV would avoid the transformation of numerous commercial cultivars, and may alleviate consumer resistance to the use of GM plants.

  19. Fighting Sharka in Peach: Current Limitations and Future Perspectives

    Science.gov (United States)

    Cirilli, Marco; Geuna, Filippo; Babini, Anna R.; Bozhkova, Valentina; Catalano, Luigi; Cavagna, Beniamino; Dallot, Sylvie; Decroocq, Véronique; Dondini, Luca; Foschi, Stefano; Ilardi, Vincenza; Liverani, Alessandro; Mezzetti, Bruno; Minafra, Angelantonio; Pancaldi, Marco; Pandolfini, Tiziana; Pascal, Thierry; Savino, Vito N.; Scorza, Ralph; Verde, Ignazio; Bassi, Daniele

    2016-01-01

    Sharka, caused by Plum Pox Virus (PPV), is by far the most important infectious disease of peach [P. persica (L.) Batsch] and other Prunus species. The progressive spread of the virus in many important growing areas throughout Europe poses serious issues to the economic sustainability of stone fruit crops, peach in particular. The adoption of internationally agreed-upon rules for diagnostic tests, strain-specific monitoring schemes and spatial–temporal modeling of virus spread, are all essential for a more effective sharka containment. The EU regulations on nursery activity should be modified based on the zone delimitation of PPV presence, limiting open-field production of propagation materials only to virus-free areas. Increasing the efficiency of preventive measures should be augmented by the short-term development of resistant cultivars. Putative sources of resistance/tolerance have been recently identified in peach germplasm, although the majority of novel resistant sources to PPV-M have been found in almond. However, the complexity of introgression from related-species imposes the search for alternative strategies. The use of genetic engineering, particularly RNA interference (RNAi)-based approaches, appears as one of the most promising perspectives to introduce a durable resistance to PPV in peach germplasm, notwithstanding the well-known difficulties of in vitro plant regeneration in this species. In this regard, rootstock transformation to induce RNAi-mediated systemic resistance would avoid the transformation of numerous commercial cultivars, and may alleviate consumer resistance to the use of GM plants. PMID:27625664

  20. Tangata whaiora/consumers perspectives on current psychiatric classification systems

    Directory of Open Access Journals (Sweden)

    Wells Debra

    2008-06-01

    Full Text Available Abstract Background A number of studies have been undertaken with the aim of considering the utility of mental health classification systems from the perspective of a variety of stakeholders. There is a lack of research on how useful consumers/tangata whaiora think these are in assisting them in their recovery. Methods Seventy service users were involved in seven focus groups in order to consider this question. Results and discussion While for clinicians diagnosing someone might be a discrete event and easily forgotten as a moment in a busy schedule, most people in this study remembered the occasion and aftermath very clearly. The overall consensus was that whether being 'diagnosed' was helpful or not, in large part, depended on how the process happened and what resulted from being 'labeled' in the person's life. Conclusion Overall, people thought that in terms of their recovery, the classification systems were tools and their utility depended on how they were used. They suggested that whatever tool was used it needed to help them make sense of their distress and provide them with a variety of supports, not just medication, to assist them to live lives that were meaningful to them.

  1. Robotics in urological surgery: evolution, current status and future perspectives.

    Science.gov (United States)

    Sivaraman, A; Sanchez-Salas, R; Prapotnich, D; Barret, E; Mombet, A; Cathala, N; Rozet, F; Galiano, M; Cathelineau, X

    2015-09-01

    Robotic surgery is rapidly evolving and has become an essential part of surgical practice in several parts of the world. Robotic technology will expand globally and most of the surgeons around the world will have access to surgical robots in the future. It is essential that we are updated about the outcomes of robot assisted surgeries which will allow everyone to develop an unbiased opinion on the clinical utility of this innovation. In this review we aim to present the evolution, objective evaluation of clinical outcomes and future perspectives of robot assisted urologic surgeries. A systematic literature review of clinical outcomes of robotic urological surgeries was made in the PUBMED. Randomized control trials, cohort studies and review articles were included. Moreover, a detailed search in the web based search engine was made to acquire information on evolution and evolving technologies in robotics. The present evidence suggests that the clinical outcomes of the robot assisted urologic surgeries are comparable to the conventional open surgical and laparoscopic results and are associated with fewer complications. However, long term results are not available for all the common robotic urologic surgeries. There are plenty of novel developments in robotics to be available for clinical use in the future. Robotic urologic surgery will continue to evolve in the future. We should continue to critically analyze whether the advances in technology and the higher cost eventually translates to improved overall surgical performance and outcomes. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Family Therapy in Poland: Development and Current Perspectives.

    Science.gov (United States)

    Józefik, Barbara; de Barbaro, Bogdan; Iniewicz, Grzegorz; Namysłowska, Irena

    2013-06-01

    The authors of the present article describe the historical context of family therapy in Poland and current issues in the field. They highlight the fact that Polish therapists first began to develop the field after coming into contact with family therapy leaders from the United States and Western Europe. With the political breakthrough of 1989, there were new opportunities for multilateral cooperation, attendance at international conferences, and the exchange of experiences. Currently, the work of Polish family therapists, the place of family therapy among other forms of psychotherapy, and the related problems and challenges do not differ from other European nations.

  3. Proteomic profiling of exosomes leads to the identification of novel biomarkers for prostate cancer

    NARCIS (Netherlands)

    D. Duijvesz (Diederick); K.E. Burnum-Johnson (Kristin); M.A. Gritsenko (Marina); A.M. Hoogland (Marije); M.S. Vredenbregt-van den Berg (Mirella); R. Willemsen (Rob); T.M. Luider (Theo); L. Paša-Tolić (Ljiljana); G.W. Jenster (Guido)

    2013-01-01

    textabstractBackground: Current markers for prostate cancer, such as PSA lack specificity. Therefore, novel biomarkers are needed. Unfortunately, the complexity of body fluids often hampers biomarker discovery. An attractive alternative approach is the isolation of small vesicles, i.e. exosomes,

  4. A Perspective on the Current State of Death Education

    Science.gov (United States)

    Wass, Hannelore

    2004-01-01

    The author offers some views on the current state of death education with focus on the sparing attention given the death education of health professionals and of grief counselors. There is need for improved integration of the knowledge accumulated in the study of death, dying, and bereavement into the basic curricula of the parent disciplines and…

  5. Central Neural Control of the Cardiovascular System: Current Perspectives

    Science.gov (United States)

    Dampney, Roger A. L.

    2016-01-01

    This brief review, which is based on a lecture presented at the American Physiological Society Teaching Refresher Course on the Brain and Systems Control as part of the Experimental Biology meeting in 2015, aims to summarize current concepts of the principal mechanisms in the brain that regulate the autonomic outflow to the cardiovascular system.…

  6. Erlotinib resistance in Lung Cancer: Current Progress and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Joy eTang

    2013-02-01

    Full Text Available Lung cancer is the most common cancer in the world. Despite modern advancements in surgeries, chemotherapies and radiotherapies over the past few years, lung cancer still remains a very difficult disease to treat. This has left the death rate from lung cancer victims largely unchanged throughout the past few decades. A key cause for the high mortality rate is the drug resistance that builds up for patients being currently treated with the chemotherapeutic agents. Although certain chemotherapeutic agents may initially effectively treat lung cancer patients, there is a high probability that there will be a reoccurrence of the cancer after the patient develops resistance to the drug. Erlotinib, the epidermal growth factor receptor (EGFR-targeting tyrosine kinase inhibitor, has been approved for localized as well as metastatic non-small cell lung cancer where it seems to be more effective in patients with EGFR mutations. Resistance to erlotinib is a common observation in clinics and this review details our current knowledge on the subject. We discuss the causes of such resistance as well as innovative research to overcome it. Evidently, new chemotherapy strategies are desperately needed in order to better treat lung cancer patients. Current research is investigating alternative treatment plans to enhance the chemotherapy that is already offered. Better insight into the molecular mechanisms behind combination therapy pathways and even single molecular pathways may help improve the efficacy of the current treatment options.

  7. Improved Vaccine against PRRSV: Current Progress and Future Perspective

    Directory of Open Access Journals (Sweden)

    Yuchen Nan

    2017-08-01

    Full Text Available Porcine reproductive and respiratory syndrome virus (PRRSV, one of the most economically significant pathogens worldwide, has caused numerous outbreaks during the past 30 years. PRRSV infection causes reproductive failure in sows and respiratory disease in growing and finishing pigs, leading to huge economic losses for the swine industry. This impact has become even more significant with the recent emergence of highly pathogenic PRRSV strains from China, further exacerbating global food security. Since new PRRSV variants are constantly emerging from outbreaks, current strategies for controlling PRRSV have been largely inadequate, even though our understanding of PRRSV virology, evolution and host immune response has been rapidly expanding. Meanwhile, practical experience has revealed numerous safety and efficacy concerns for currently licensed vaccines, such as shedding of modified live virus (MLV, reversion to virulence, recombination between field strains and MLV and failure to elicit protective immunity against heterogeneous virus. Therefore, an effective vaccine against PRRSV infection is urgently needed. Here, we systematically review recent advances in PRRSV vaccine development. Antigenic variations resulting from PRRSV evolution, identification of neutralizing epitopes for heterogeneous isolates, broad neutralizing antibodies against PRRSV, chimeric virus generated by reverse genetics, and novel PRRSV strains with interferon-inducing phenotype will be discussed in detail. Moreover, techniques that could potentially transform current MLV vaccines into a superior vaccine will receive special emphasis, as will new insights for future PRRSV vaccine development. Ultimately, improved PRRSV vaccines may overcome the disadvantages of current vaccines and minimize the PRRS impact to the swine industry.

  8. Current Perspectives in Teaching English for Specific Purposes

    Science.gov (United States)

    Garcia Laborda, Jesus; Litzler, Mary Frances

    2015-01-01

    Interest in Languages for Specific Purposes (LSP)courses has grown in recent years (Harding, 2007). For this reason a paper on the current situation in the field is of relevance. The present article provides a discussion of English for Specific Purposes and it does so by reviewing the history and background of this area of teaching, proposing a…

  9. Wave energy in Europe: current status and perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Clement, Alain [Exole Centrale de Nantes, Nantes, (France); McCullen, Pat [ESBI (Ireland); Falcao, Antonio [IST, Lisboa (Portugal); Firoentino, Antonio [Ponte di Archimede nello Streto di Messina, Messina (Italy); Gardner, Fred [Teamwork Technology (Netherlands); Hammarlund, Karin [Hammarlund A., Konsult (Sweden); Lemonis, George [Centre for Renewable Energy Sources, Attika (Greece); Lewis, Tony [University College Cork, Cork (Ireland)

    2002-10-01

    The progress in wave energy conversion in Europe during the past ten years is reviewed, and current activities and initiatives in the wave energy sector at National and Union level are described. Other important activities worldwide are summarized. The technical and economic status in wave energy conversion is outlined, and important wave energy developments are presented.

  10. Neuropsychological Assessment and Rehabilitation: Historical Development and Current Perspectives

    OpenAIRE

    Amer Cavalheiro Hamdan; Ana Paula Almeida de Pereira; Tatiana Izabele Jaworski de Sá Riechi

    2011-01-01

    The present paper aimed to briefly present a historical view of Neuropsychology and later, to propose research topics in Brazil. Neuropsychology history encompassed at least three major themes: the cardiac hypothesis versus the brain hypothesis, localizationism versus holism and functionalism versus cognitivism. These themes influenced research in neuropsychology and based current practice. Furthermore, two important aspects of neuropsychology are discussed: neuropsychological assessment in d...

  11. Machine perfusion for improving outcomes following renal transplant: current perspectives

    Directory of Open Access Journals (Sweden)

    Cannon RM

    2016-03-01

    Full Text Available Robert M Cannon,1 Glen A Franklin1,2 1The Hiram C Polk Jr MD Department of Surgery, University of Louisville, 2Kentucky Organ Donor Affiliates, Louisville, KY, USAAbstract: There is a disparity between the number of kidneys available for transplantation and the number of patients awaiting an organ while on dialysis. The current kidney waiting list in the US contains more than 100,000 patients. This need has led to the inclusion of older donors with worsening renal function, as well as greater utilization of kidneys from non-heartbeating (donation after cardiac death donors. Coinciding with this trend has been a growing interest in technology to improve the function of these more marginal organs, the most important of which currently is machine perfusion (MP of donated kidneys after procurement. While this technology has no standard guidelines currently for comprehensive use, there are many studies that demonstrate higher organ yield and function after a period of MP. Particularly with the older donor and during donation after cardiac death cases, MP may offer some significant benefits. This manuscript reviews all of the current literature regarding MP and its role in renal transplantation. We will discuss both the experience in Europe and the US using machine perfusion for donated kidneys.Keywords: machine perfusion, renal transplantation, kidney pumping, renal failure, organ donation

  12. Silicon and Plants: Current Knowledge and Technological Perspectives.

    Science.gov (United States)

    Luyckx, Marie; Hausman, Jean-Francois; Lutts, Stanley; Guerriero, Gea

    2017-01-01

    Elemental silicon (Si), after oxygen, is the second most abundant element in the earth's crust, which is mainly composed of silicates. Si is not considered essential for plant growth and development, however, increasing evidence in the literature shows that this metalloid is beneficial to plants, especially under stress conditions. Indeed Si alleviates the toxic effects caused by abiotic stresses, e.g., salt stress, drought, heavy metals, to name a few. Biogenic silica is also a deterrent against herbivores. Additionally, Si ameliorates the vigor of plants and improves their resistance to exogenous stresses. The protective role of Si was initially attributed to a physical barrier fortifying the cell wall (e.g., against fungal hyphae penetration), however, several studies have shown that the action of this element on plants is far more complex, as it involves a cross-talk with the cell interior and an effect on plant metabolism. In this study the beneficial role of Si on plants will be discussed, by reviewing the available data in the literature. Emphasis will be given to the protective role of Si during (a)biotic stresses and in this context both priming and the effects of Si on endogenous phytohormones will be discussed. A whole section will be devoted to the use of silica (SiO2) nanoparticles, in the light of the interest that nanotechnology has for agriculture. The paper also discusses the potential technological aspects linked to the use of Si in agriculture and to modify/improve the physical parameters of plant fibers. The study indeed provides perspectives on the use of Si to increase the yield of fiber crops and to improve the thermal stability and tensile strength of natural fibers.

  13. Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice

    Energy Technology Data Exchange (ETDEWEB)

    Geiger, Adolf, E-mail: ageiger@dreirosen-pharma.com; Walker, Audrey, E-mail: awalker@dreirosen-pharma.com; Nissen, Erwin, E-mail: enissen@dreirosen-pharma.com

    2015-11-13

    Diabetic ulcers represent a substantial societal and healthcare burden worldwide and scarcely respond to current treatment strategies. This study was addressed to evaluate the therapeutic potential of exosomes secreted by human circulating fibrocytes, a population of mesenchymal progenitors involved in normal wound healing via paracrine signaling. The exosomes released from cells sequentially stimulated with platelet-derived growth factor-BB and transforming growth factor-β1, in the presence of fibroblast growth factor 2, did not show potential immunogenicity. These exosomes exhibited in-vitro proangiogenic properties, activated diabetic dermal fibroblasts, induced the migration and proliferation of diabetic keratinocytes, and accelerated wound closure in diabetic mice in vivo. Important components of the exosomal cargo were heat shock protein-90α, total and activated signal transducer and activator of transcription 3, proangiogenic (miR-126, miR-130a, miR-132) and anti-inflammatory (miR124a, miR-125b) microRNAs, and a microRNA regulating collagen deposition (miR-21). This proof-of-concept study demonstrates the feasibility of the use of fibrocytes-derived exosomes for the treatment of diabetic ulcers. - Highlights: • Fibrocytes have shown potent wound healing properties in vitro and in vivo. • Their clinical use is precluded by low numbers and antigen-presenting function. • We isolated exosomes with no immunogenicity potential from human fibrocytes. • Their cargo included microRNAs and proteins that are known healing promoters. • They accelerated wound closure in diabetic mice in a dose-dependent manner.

  14. Microbial production of hyaluronic acid: current state, challenges, and perspectives

    Directory of Open Access Journals (Sweden)

    Liu Long

    2011-11-01

    Full Text Available Abstract Hyaluronic acid (HA is a natural and linear polymer composed of repeating disaccharide units of β-1, 3-N-acetyl glucosamine and β-1, 4-glucuronic acid with a molecular weight up to 6 million Daltons. With excellent viscoelasticity, high moisture retention capacity, and high biocompatibility, HA finds a wide-range of applications in medicine, cosmetics, and nutraceuticals. Traditionally HA was extracted from rooster combs, and now it is mainly produced via streptococcal fermentation. Recently the production of HA via recombinant systems has received increasing interest due to the avoidance of potential toxins. This work summarizes the research history and current commercial market of HA, and then deeply analyzes the current state of microbial production of HA by Streptococcus zooepidemicus and recombinant systems, and finally discusses the challenges facing microbial HA production and proposes several research outlines to meet the challenges.

  15. Short-term tocolytics for preterm delivery – current perspectives

    Directory of Open Access Journals (Sweden)

    Haas DM

    2014-03-01

    Full Text Available David M Haas, Tara Benjamin, Renata Sawyer, Sara K QuinneyDepartment of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USAAbstract: Administration of short-term tocolytic agents can prolong pregnancy for women in preterm labor. Prolonging pregnancy has many benefits because it allows for other proven interventions, such as antenatal corticosteroid administration, to be accomplished. This review provides an overview of currently utilized tocolytic agents and the evidence demonstrating their efficacy for prolonging pregnancy by at least 48 hours. General pharmacological principles for the clinician regarding drugs in pregnancy are also briefly discussed. In general, while the choice of the best first-line short-term tocolytic drug is not clear, it is evident that use of these agents has a clear place in current obstetric therapeutics.Keywords: tocolytics, short-term, preterm delivery

  16. Current perspectives in proteomic analysis of abiotic stress in Grapevines

    Directory of Open Access Journals (Sweden)

    Iniga Seraphina George

    2014-12-01

    Full Text Available Grapes are an important crop plant which forms the basis of a globally important industry. Grape and wine production is particularly vulnerable to environmental and climatic fluctuations, which makes it essential for us to develop a greater understanding of the molecular level responses of grape plants to various abiotic stresses. The completion of the initial grape genome sequence in 2007 has led to a significant increase in research on grapes using proteomics approaches. In this article, we discuss some of the current research on abiotic stress in grapevines, in the context of abiotic stress research in other plant species. We also highlight some of the current limitations in grapevine proteomics and identify areas with promising scope for potential future research.

  17. Current perspectives: the impact of cyberbullying on adolescent health

    OpenAIRE

    Nixon, Charisse L

    2014-01-01

    Charisse L Nixon Pennsylvania State University, the Behrend College, Erie, PA, USA Abstract: Cyberbullying has become an international public health concern among adolescents, and as such, it deserves further study. This paper reviews the current literature related to the effects of cyberbullying on adolescent health across multiple studies worldwide and provides directions for future research. A review of the evidence suggests that cyberbullying poses a threat to adolescents' health...

  18. [EU law on marketing authorization of medicines. History, current state of development and perspectives].

    Science.gov (United States)

    Nettesheim, Martin

    2008-07-01

    The article describes the development of EU policies and regulations on the marketing authorization of medicines. First, it describes the changing perspective of the EU towards the regulation of such authorizations. While its original focus was on the liberalization of national markets, it has today assumed overarching political responsibility for the development and marketing of medicines. Second, the article describes the current, rather fragmented regulatory system. Finally, political perspectives on the integration of markets for medicines are developed.

  19. Current states and perspectives of Czech educational research

    Directory of Open Access Journals (Sweden)

    Tomáš Janík

    2010-06-01

    Full Text Available The aim of the review study is to evaluate the current state of Czech educationalresearch and to offer possibilities of its further development. The paper has threeparts. In the first part, the author presents the context of the topic: the current changesin the financing of research and development in the Czech Republic; the avoiding ofthe term (social science is discussed along with the issue of institutional financing ofresearch and the various presently up-to-date methodologies of quality assessment inresearch. In the second part, the author analyses the current state of Czech educationalresearch – previous analyses of J. Pr°ucha, J. Mareš and E. Walterová and those carriedout by the Educational Research Centre are briefly summarised. In the third part, possibilitiesof further development of Czech educational research are offered. Developinga knowledge base of educational sciences is used as an example. First the nature andsubject of knowledge that is produced by research is analysed, then the difference betweenpedagogical research and research in education is discussed. Towards the end,relevant approaches are discussed along with research areas and types of knowledgeacquired by research.

  20. Risk definition and management strategies in retinoblastoma: current perspectives

    Directory of Open Access Journals (Sweden)

    Ghassemi F

    2015-06-01

    Full Text Available Fariba Ghassemi, Alireza Khodabande Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Tehran Province, Islamic Republic of Iran Abstract: This manuscript focuses on high-risk factors of metastatic disease in retinoblastoma and evaluation of the current treatments of retinoblastoma. Presence of histopathologic high-risk factors is associated with a higher risk of local recurrence and systemic metastasis. Currently, globe-sparing therapies, including systemic chemotherapy, intra-arterial chemoreduction, intravitreal chemotherapy, focal consolidation, and combination therapies, are being used and investigated actively. Major advances are being made in the diagnosis and management of retinoblastoma that will lead to improved morbidity and mortality rates in patients with retinoblastoma. By saving the globes, fronting with some high-risk factors for metastasis would be inevitable. International multi-institutional prospective studies could resolve current uncertainties regarding the main tumor treatment regimens for each patient and indications for chemoprophylaxis for high-risk-factor-bearing retinoblastoma cases. Keywords: retinoblastoma, intra-arterial chemotherapy, systemic chemotherapy

  1. Placental exosomes during gestation: liquid biopsies carrying signals for the regulation of human parturition.

    Science.gov (United States)

    Salomon, Carlos; Nuzhat, Zarin; Dixon, Christopher L; Menon, Ramkumar

    2018-01-25

    . These can in turn interact with either adjacent or distal cells to reprogram their phenotype and regulate their function. Many of the pro-parturition proinflammatory mediators reach maternal compartments from the fetal side via circulation, but major impediments remain, such as degradation at various levels and limited half-life in circulation. Recent findings suggest that a more effective mode of communication and signal transport is through exosomes, where signals are protected and will not succumb to degradation. Thus, understanding how exosomes regulate key events throughout pregnancy and parturition will provide an opportunity to understand the mechanisms involved in the maternal and fetal metabolic adaptations during normal and pathological pregnancies. Subsequently, this will assist in identifying those pregnancies at risk of developing complications. This may also allow more appropriate modifications of their clinical management. This review will hence examine the current body of data to summarise our understanding of how signaling pathways lead to the beginning of parturition. In addition, we propose that extracellular vesicles, namely exosomes, may be an integral component of these signaling events by transporting specific signals to prepare the maternal physiology to initiate parturition. Understanding these signals and their mechanisms in normal term pregnancies can provide insight into pathological activation of these signals, which can cause spontaneous preterm parturition. Hence, this review expands on our knowledge of exosomes as professional carriers of fetal signals to instigate human parturition. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Exosome-associated hepatitis C virus in cell cultures and patient plasma

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ziqing [Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Zhang, Xiugen [Department of Cell Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States); Yu, Qigui [Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); He, Johnny J., E-mail: johnny.he@unthsc.edu [Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Department of Cell Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States)

    2014-12-12

    Highlights: • HCV occurs in both exosome-free and exosome-associated forms. • Exosome-associated HCV is infectious and resistant to neutralizing antibodies. • More exosome-associated HCV than exosome-free HCV is present in patient plasma. - Abstract: Hepatitis C virus (HCV) infects its target cells in the form of cell-free viruses and through cell–cell contact. Here we report that HCV is associated with exosomes. Using highly purified exosomes and transmission electron microscopic imaging, we demonstrated that HCV occurred in both exosome-free and exosome-associated forms. Exosome-associated HCV was infectious and resistant to neutralization by an anti-HCV neutralizing antibody. There were more exosome-associated HCV than exosome-free HCV detected in the plasma of HCV-infected patients. These results suggest exosome-associated HCV as an alternative form for HCV infection and transmission.

  3. Vitamin D in pregnancy: current perspectives and future directions.

    Science.gov (United States)

    Kiely, Mairead; Hemmingway, Andrea; O'Callaghan, Karen M

    2017-06-01

    As neonatal vitamin D status is determined by circulating maternal 25-hydroxyvitamin D [25(OH)D] concentrations, prevention of maternal vitamin D deficiency during pregnancy is essential for the avoidance of neonatal deficiency. However, a high prevalence of vitamin D deficiency has been extensively reported among gravidae and neonates from ethnic minorities and white populations resident at high latitude. Currently, regulatory authorities recommend vitamin D intakes for pregnant women that are similar to non-pregnant adults of the same age, at 10-15 µg/day (400-600 IU), to meet 25(OH)D thresholds of 25-50 nmol/liter. The lack of pregnancy-specific dietary recommendations is due to inadequate data indicating whether nutritional requirements for vitamin D during pregnancy differ from the non-pregnant state. In addition, there are few dose-response studies to determine the maternal 25(OH)D response to vitamin D intake throughout pregnancy at high latitude. These data are also required to determine vitamin D requirements during pregnancy for prevention of neonatal deficiency, an outcome which is likely to require a higher maternal 25(OH)D concentration than prevention of maternal deficiency only. With regard to the impact of vitamin D on perinatal health outcomes, which could guide pregnancy-specific 25(OH)D thresholds, dietary intervention studies to date have been inconsistent and recent systematic reviews have highlighted issues of low quality and a high risk of bias as drawbacks in the trial evidence to date. Many observational studies have been hampered by a reliance on retrospective data, unclear reporting, suboptimal clinical phenotyping and incomplete subject characterization. Current investigations of vitamin D metabolism during pregnancy have potentially exciting implications for clinical research. This paper provides an update of current dietary recommendations for vitamin D in pregnant women and a synopsis of the evidence relating vitamin D status with

  4. The MAO NASU Plate Archive Database. Current Status and Perspectives

    Science.gov (United States)

    Pakuliak, L. K.; Sergeeva, T. P.

    2006-04-01

    The preliminary online version of the database of the MAO NASU plate archive is constructed on the basis of the relational database management system MySQL and permits an easy supplement of database with new collections of astronegatives, provides a high flexibility in constructing SQL-queries for data search optimization, PHP Basic Authorization protected access to administrative interface and wide range of search parameters. The current status of the database will be reported and the brief description of the search engine and means of the database integrity support will be given. Methods and means of the data verification and tasks for the further development will be discussed.

  5. A current perspective on antimicrobial resistance in Southeast Asia.

    Science.gov (United States)

    Zellweger, Raphaël M; Carrique-Mas, Juan; Limmathurotsakul, Direk; Day, Nicholas P J; Thwaites, Guy E; Baker, Stephen

    2017-11-01

    Southeast Asia, a vibrant region that has recently undergone unprecedented economic development, is regarded as a global hotspot for the emergence and spread of antimicrobial resistance (AMR). Understanding AMR in Southeast Asia is crucial for assessing how to control AMR on an international scale. Here we (i) describe the current AMR situation in Southeast Asia, (ii) explore the mechanisms that make Southeast Asia a focal region for the emergence of AMR, and (iii) propose ways in which Southeast Asia could contribute to a global solution. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  6. Rotavirus vaccines: current global impact and future perspectives

    Science.gov (United States)

    Burnett, Eleanor; Yen, Catherine; Tate, Jacqueline E; Parashar, Umesh D

    2016-01-01

    As of May 2016, 81 countries have introduced Rotarix or RotaTeq rotavirus vaccines into their national immunization program. Despite initially slow uptake in some countries and differences in vaccine effectiveness (VE) between high-, low- and middle-income countries, impact of the vaccines has been swift and striking in all settings, with good VE against vaccine-type and nonvaccine-type strains. Newly published research indicates poor nutrition is associated with decreased VE and breastfeeding at the time of vaccination does not affect vaccine response. Vaccines in development and proposed alternate schedules also promise to address limitations of the current vaccines and optimize rotavirus disease prevention. PMID:27840654

  7. Current therapies and future perspectives in subacute sclerosing panencephalitis.

    Science.gov (United States)

    Tatli, Burak; Ekici, Bariş; Ozmen, Meral

    2012-04-01

    Subacute sclerosing panencephalitis is a progressive neurological disorder of children and young adults caused by a measles virus that became defective by persisting in the host. According to the results of clinical trials, antiviral and/or immunomodulatory therapy can slow the progression of the disease and improve life expectancy in patients. However, its long-term effects and eventual outcome remain debatable due to conflicting results and its lack of effect on the rapidly progressive form of the disease. Possible future therapies for subacute sclerosing panencephalitis are RNAi and antiapoptotic agents, which are currently in the hypothetical and experimental stages of research.

  8. Challenges to Global Implementation of Infrared Thermography Technology: Current Perspective.

    Science.gov (United States)

    Shterenshis, Michael

    2017-01-01

    Medical infrared thermography (IT) produces an image of the infrared waves emitted by the human body as part of the thermoregulation process that can vary in intensity based on the health of the person. This review analyzes recent developments in the use of infrared thermography as a screening and diagnostic tool in clinical and nonclinical settings, and identifies possible future routes for improvement of the method. Currently, infrared thermography is not considered to be a fully reliable diagnostic method. If standard infrared protocol is established and a normative database is available, infrared thermography may become a reliable method for detecting inflammatory processes.

  9. Nanomaterials in Lubricants: An Industrial Perspective on Current Research

    Directory of Open Access Journals (Sweden)

    Boris Zhmud

    2013-11-01

    Full Text Available This paper presents an overview on the use of various classes of nanomaterials in lubricant formulations. The following classes of nanomaterials are considered: fullerenes, nanodiamonds, ultradispersed boric acid and polytetrafluoroethylene (PTFE. Current advances in using nanomaterials in engine oils, industrial lubricants and greases are discussed. Results of numerous studies combined with formulation experience of the authors strongly suggest that nanomaterials do indeed have potential for enhancing certain lubricant properties, yet there is a long way to go before balanced formulations are developed.

  10. Indirect dark matter searches: current status and perspectives

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    Many theoretical ideas for the particle nature of dark matter exist. The  most popular models often predict that dark matter particles self-annihilate or decay, giving rise to potentially detectable signatures in astronomical observations.  I will summarize the current status of searches for such signatures and critically reassess recent claims for dark matter signals.  I will further provide an outlook on anticipated developments in the next 10 years, and discuss new methods to facilitate strategy development.

  11. Brown carbon in the cryosphere: Current knowledge and perspective

    Directory of Open Access Journals (Sweden)

    Guang-Ming Wu

    2016-03-01

    Full Text Available Recently, the light-absorbing organic carbon, i.e., brown carbon (BrC, has received an increasing attention, because they could significantly absorb the solar radiation in the range of short wavelengths rather than the purely scattering effect. BrC is ubiquitous in the troposphere. It could undergo long range transport within the atmospheric circulation. After the deposition on the surface of snow or ice in the cryospheric region, as the major light absorbing impurities with black carbon and dust, BrC could reduce the snow albedo and accelerate the glacier melting. In this context, this paper summarized the current knowledge of BrC (in aerosols and snow in the cryospheric regions including the Arctic, Antarctic, and Alpines. Although some works have been conducted in those region, the current dataset on the optical properties of BrC like Absorption Ångström Exponent (AAE and Mass Absorption Efficiency (MAE is still limited, which hampers stimulating an accurate evaluation of its climate effects. Especially in the Himalayas and Tibetan Plateau, where very limited information concerning BrC is available. Considering biomass burning as a dominant source of BrC, a large amount of emissions from biomass burning in South Asia could reach the Himalayas and Tibetan Plateau, where the climate effect of BrC merits more investigation in the future.

  12. Current advances and future perspectives in extrusion-based bioprinting.

    Science.gov (United States)

    Ozbolat, Ibrahim T; Hospodiuk, Monika

    2016-01-01

    Extrusion-based bioprinting (EBB) is a rapidly growing technology that has made substantial progress during the last decade. It has great versatility in printing various biologics, including cells, tissues, tissue constructs, organ modules and microfluidic devices, in applications from basic research and pharmaceutics to clinics. Despite the great benefits and flexibility in printing a wide range of bioinks, including tissue spheroids, tissue strands, cell pellets, decellularized matrix components, micro-carriers and cell-laden hydrogels, the technology currently faces several limitations and challenges. These include impediments to organ fabrication, the limited resolution of printed features, the need for advanced bioprinting solutions to transition the technology bench to bedside, the necessity of new bioink development for rapid, safe and sustainable delivery of cells in a biomimetically organized microenvironment, and regulatory concerns to transform the technology into a product. This paper, presenting a first-time comprehensive review of EBB, discusses the current advancements in EBB technology and highlights future directions to transform the technology to generate viable end products for tissue engineering and regenerative medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Current Perspectives on Long-term Obesity Pharmacotherapy.

    Science.gov (United States)

    Wharton, Sean

    2016-04-01

    Approximately 1 in 4 adult Canadians are obese and, thus, are at an elevated risk for developing type 2 diabetes, cardiovascular disease and other conditions. Current treatment guidelines recommend that obese individuals lose 5% to 10% of their starting weights to minimize the risk factors for cardiovascular disease and reduce the risk for developing type 2 diabetes or hypertension. All obesity-management strategies involve lifestyle management, but few patients will lose a significant amount of weight and manage to keep it off over the long term using just this strategy. Bariatric surgery is associated with significant long-term weight loss but is restricted to subjects with very high body mass indices, who often wait many years to undergo the procedure. Recent breakthroughs in understanding the mechanisms underlying the development and maintenance of elevated body fat have led to the arrival of new obesity pharmacotherapies. These novel antiobesity therapies, which work by reducing energy intake or through increasing satiety, decreasing hunger, or reducing absorption of calories, may be used indefinitely once patients have demonstrated significant responses (usually defined as ≥5% weight loss) over the first 12 weeks of treatment. To date, 2 long-term obesity pharmacotherapies have been approved and are available in Canada: liraglutide and orlistat. Here, I summarize the mechanisms and clinical features of medications for long-term obesity management that are available in Canada, as well as those available in other jurisdictions or are currently in development. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  14. Soil ecotoxicology in Latin America: Current research and perspectives.

    Science.gov (United States)

    Niemeyer, Júlia Carina; Chelinho, Sónia; Sousa, José Paulo

    2017-07-01

    Soils from some Latin American countries support the highest biodiversity levels on the planet and simultaneously have some of the most serious environmental impacts attributed to both historical and current agricultural practices and industrial activities. Soil contamination has resulted from intensive use of pesticides, extensive mining and other industrial activities, and uncontrolled management of waste within inappropriate regulatory frameworks. The present study presents an overview of the scientific research on soil ecotoxicology conducted in Latin America, summarizing the recent advances and highlighting the needs for further refinements in this research field. Most of the contributions to the scientific literature have been from Brazil. The most investigated issue is the ecotoxicity of pesticides and earthworms, which were the organisms most frequently used as test species. Needs identified by Latin American researchers include methods and procedures for: 1) identifying and collecting natural soils to be used as reference test-substrates in tests, 2) identifying and discerning the range of sensitivities of native test species to soil contaminants, 3) developing environmental guidelines applicable to tropical/subtropical conditions, and 4) developing methods and procedures for higher tier testing for full development and implementation of environmental risk assessment schemes. The protection of Latin American soils, including provision of goods and services, is currently framed in legislation and other regulations, but implementation requires significant improvement and additional training programs. Environ Toxicol Chem 2017;36:1795-1810. © 2017 SETAC. © 2017 SETAC.

  15. Gold nanoparticles with patterned surface monolayers for nanomedicine: current perspectives.

    Science.gov (United States)

    Pengo, Paolo; Şologan, Maria; Pasquato, Lucia; Guida, Filomena; Pacor, Sabrina; Tossi, Alessandro; Stellacci, Francesco; Marson, Domenico; Boccardo, Silvia; Pricl, Sabrina; Posocco, Paola

    2017-12-01

    Molecular self-assembly is a topic attracting intense scientific interest. Various strategies have been developed for construction of molecular aggregates with rationally designed properties, geometries, and dimensions that promise to provide solutions to both theoretical and practical problems in areas such as drug delivery, medical diagnostics, and biosensors, to name but a few. In this respect, gold nanoparticles covered with self-assembled monolayers presenting nanoscale surface patterns-typically patched, striped or Janus-like domains-represent an emerging field. These systems are particularly intriguing for use in bio-nanotechnology applications, as presence of such monolayers with three-dimensional (3D) morphology provides nanoparticles with surface-dependent properties that, in turn, affect their biological behavior. Comprehensive understanding of the physicochemical interactions occurring at the interface between these versatile nanomaterials and biological systems is therefore crucial to fully exploit their potential. This review aims to explore the current state of development of such patterned, self-assembled monolayer-protected gold nanoparticles, through step-by-step analysis of their conceptual design, synthetic procedures, predicted and determined surface characteristics, interactions with and performance in biological environments, and experimental and computational methods currently employed for their investigation.

  16. Neoplastic stem cells: current concepts and clinical perspectives.

    Science.gov (United States)

    Schulenburg, Axel; Brämswig, Kira; Herrmann, Harald; Karlic, Heidrun; Mirkina, Irina; Hubmann, Rainer; Laffer, Sylvia; Marian, Brigitte; Shehata, Medhat; Krepler, Clemens; Pehamberger, Hubert; Grunt, Thomas; Jäger, Ulrich; Zielinski, Christoph C; Valent, Peter

    2010-11-01

    Neoplastic stem cells have initially been characterized in myeloid leukemias where NOD/SCID mouse-repopulating progenitors supposedly reside within a CD34+/Lin- subset of the malignant clone. These progenitors are considered to be self-renewing cells responsible for the in vivo long-term growth of neoplastic cells in leukemic patients. Therefore, these cells represent an attractive target of therapy. In some lymphoid leukemias, NOD/SCID mouse-repopulating cells were also reported to reside within the CD34+/Lin- subfraction of the clone. More recently, several attempts have been made to transfer the cancer stem cell concept to solid tumors and other non-hematopoietic neoplasms. In several of these tumors, the cell surface antigens AC133 (CD133) and CD44 are considered to indicate the potential of a cell to initiate permanent tumor formation in vivo. However, several questions concerning the phenotype, self-renewal capacity, stroma-dependence, and other properties of cancer- or leukemia-initiating cells remain to be solved. The current article provides a summary of our current knowledge on neoplastic (cancer) stem cells, with special emphasis on clinical implications and therapeutic options as well as a discussion about conceptual and technical limitations. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  17. Neonatal abstinence syndrome: Historical perspective, current focus, future directions.

    Science.gov (United States)

    Jones, Hendrée E; Fielder, Andrea

    2015-11-01

    Neonatal abstinence syndrome (NAS) occurs following prenatal opioid exposure. It is characterized by signs and symptoms indicating central nervous system hyperirritability and autonomic nervous system, gastrointestinal tract, and respiratory system dysfunction. This article: (1) briefly reviews NAS history, including initial identification, assessment, and treatment efforts; (2) summarizes the current status of and current issues surrounding recent NAS assessment and treatment, and (3) details future directions in NAS conceptualization, measurement, and treatment. Mortality rate estimates in neonates treated for NAS exceeded 33%, and surpassed 90% for un-treated infants during the late-1800s until the mid-1900s. The focus of both assessment and treatment over the past 50years is predominantly due to two forces. First, methadone pharmacotherapy for "heroin addiction" led to women in methadone maintenance programs who were, or became pregnant. The second was defining NAS and developing a measure of neonatal withdrawal, the Neonatal Abstinence Scoring System (NASS). Various NAS treatment protocols were based on the NASS as well as other NAS measures. Future research must focus on psychometrically sound screening and assessment measures of neonatal opioid withdrawal for premature, term and older infants, measuring and treating possible withdrawal from non-opioids, particularly benzodiazepines, integrated non-pharmacological treatment of NAS, weight-based versus symptom-based treatment of NAS, and second-line treatment for NAS. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. A perspective on microarrays: current applications, pitfalls, and potential uses.

    Science.gov (United States)

    Jaluria, Pratik; Konstantopoulos, Konstantinos; Betenbaugh, Michael; Shiloach, Joseph

    2007-01-25

    With advances in robotics, computational capabilities, and the fabrication of high quality glass slides coinciding with increased genomic information being available on public databases, microarray technology is increasingly being used in laboratories around the world. In fact, fields as varied as: toxicology, evolutionary biology, drug development and production, disease characterization, diagnostics development, cellular physiology and stress responses, and forensics have benefiting from its use. However, for many researchers not familiar with microarrays, current articles and reviews often address neither the fundamental principles behind the technology nor the proper designing of experiments. Although, microarray technology is relatively simple, conceptually, its practice does require careful planning and detailed understanding of the limitations inherently present. Without these considerations, it can be exceedingly difficult to ascertain valuable information from microarray data. Therefore, this text aims to outline key features in microarray technology, paying particular attention to current applications as outlined in recent publications, experimental design, statistical methods, and potential uses. Furthermore, this review is not meant to be comprehensive, but rather substantive; highlighting important concepts and detailing steps necessary to conduct and interpret microarray experiments. Collectively, the information included in this text will highlight the versatility of microarray technology and provide a glimpse of what the future may hold.

  19. A perspective on microarrays: current applications, pitfalls, and potential uses

    Directory of Open Access Journals (Sweden)

    Betenbaugh Michael

    2007-01-01

    Full Text Available Abstract With advances in robotics, computational capabilities, and the fabrication of high quality glass slides coinciding with increased genomic information being available on public databases, microarray technology is increasingly being used in laboratories around the world. In fact, fields as varied as: toxicology, evolutionary biology, drug development and production, disease characterization, diagnostics development, cellular physiology and stress responses, and forensics have benefiting from its use. However, for many researchers not familiar with microarrays, current articles and reviews often address neither the fundamental principles behind the technology nor the proper designing of experiments. Although, microarray technology is relatively simple, conceptually, its practice does require careful planning and detailed understanding of the limitations inherently present. Without these considerations, it can be exceedingly difficult to ascertain valuable information from microarray data. Therefore, this text aims to outline key features in microarray technology, paying particular attention to current applications as outlined in recent publications, experimental design, statistical methods, and potential uses. Furthermore, this review is not meant to be comprehensive, but rather substantive; highlighting important concepts and detailing steps necessary to conduct and interpret microarray experiments. Collectively, the information included in this text will highlight the versatility of microarray technology and provide a glimpse of what the future may hold.

  20. [The relationship between sleep and obesity: current perspective].

    Science.gov (United States)

    Piskáčková, Zlata; Forejt, Martin; Martykánová, Lucie

    2012-01-01

    Disruption of circadian rhythms negatively affects regulation of metabolism and energy homeostasis. Disrupted metabolism in response to disrupted biological rhythms might lead, together with genetic background, to obesity and to other health complications. Results of epidemiologic surveys are consistent with mechanistic theory showing the interconnection between the biological rhythms, sleep and metabolism. Epidemiologic surveys confirm that sleep duration of less than 6 hours increases significantly the risk of obesity. Systematic reviews of epidemiologic surveys examining association of sleep and obesity refer to large heterogeneity in involved subjects, methodological approaches of measuring obesity and sleep, and confounders. Design of study plays also essential role in interpretation and definition of causal relationship. Reduced sleep duration in relation to obesity is in the literature discussed from different points of view: 1. as a possible primary cause of obesity, 2. as a result of comorbidities resulting from obesity and 3. as an accompanied part of the third factor contributing to obesity (e.g. long working hours, chronic emotional stress, overusing of media). Causal relationship between sleep and obesity is not yet fully elucidated, however the association is supposed to be bidirectional. The article gives an overview of current knowledge concerning the influence of sleep on the development of obesity and points to the critical points of current research.

  1. [Current status and future perspectives of hepatocyte transplantation].

    Science.gov (United States)

    Pareja, Eugenia; Cortés, Miriam; Gómez-Lechón, M José; Maupoey, Javier; San Juan, Fernando; López, Rafael; Mir, Jose

    2014-02-01

    The imbalance between the number of potential beneficiaries and available organs, originates the search for new therapeutic alternatives, such as Hepatocyte transplantation (HT).Even though this is a treatment option for these patients, the lack of unanimity of criteria regarding indications and technique, different cryopreservation protocols, as well as the different methodology to assess the response to this therapy, highlights the need of a Consensus Conference to standardize criteria and consider future strategies to improve the technique and optimize the results.Our aim is to review and update the current state of hepatocyte transplantation, emphasizing the future research attempting to solve the problems and improve the results of this treatment. Copyright © 2013 AEC. Published by Elsevier Espana. All rights reserved.

  2. Obesity and hypertension in Latin America: Current perspectives.

    Science.gov (United States)

    Ruilope, L M; Nunes Filho, A C B; Nadruz, W; Rodríguez Rosales, F F; Verdejo-Paris, J

    2018-01-17

    In the countries of Central America, South America and the Caribbean, there has been a dramatic rise in obesity, the metabolic syndrome, hypertension and other cardiovascular risk factors in the last few decades. Epidemiological evidence highlights a consistent correlation between obesity and hypertension, and the presence of obesity predisposes an individual to a greater risk of hypertension although the mechanisms remain unclear. Obesity and hypertension are two key drivers of the cardio-renal disease continuum, and patients with uncontrolled cardiovascular risk in their mid-life will likely have an increased risk of clinical cardiovascular and renal outcomes in old age. This article summarizes the current status for the prevalence and consequences of obesity and hypertension in Latin America, with the aim of initiating a call to action to all stakeholders for greater implementation of primary prevention strategies, particularly in the young. Copyright © 2018 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Environmental application of biochar: Current status and perspectives.

    Science.gov (United States)

    Oliveira, Fernanda R; Patel, Anil K; Jaisi, Deb P; Adhikari, Sushil; Lu, Hui; Khanal, Samir Kumar

    2017-12-01

    In recent years, there has been a significant interest on biochar for various environmental applications, e.g., pollutants removal, carbon sequestration, and soil amelioration. Biochar has several unique properties, which makes it an efficient, cost-effective and environmentally-friendly material for diverse contaminants removal. The variability in physicochemical properties (e.g., surface area, microporosity, and pH) provides an avenue for biochar to maximize its efficacy to targeted applications. This review aims to highlight the vital role of surface architecture of biochar in different environmental applications. Particularly, it provides a critical review of current research updates related to the pollutants interaction with surface functional groups of biochars and the effect of the parameters variability on biochar attributes pertinent to specific pollutants removal, involved mechanisms, and competence for these removals. Moreover, future research directions of biochar research are also discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. OMICS: Current and future perspectives in reproductive medicine and technology.

    Science.gov (United States)

    Egea, Rocío Rivera; Puchalt, Nicolás Garrido; Escrivá, Marcos Meseguer; Varghese, Alex C

    2014-04-01

    Many couples present fertility problems at their reproductive age, and although in the last years, the efficiency of assisted reproduction techniques has increased, these are still far from being 100% effective. A key issue in this field is the proper assessment of germ cells, embryos and endometrium quality, in order to determine the actual likelihood to succeed. Currently available analysis is mainly based on morphological features of oocytes, sperm and embryos and although these strategies have improved the results, there is an urgent need of new diagnostic and therapeutic tools. The emergence of the - OMICS technologies (epigenomics, genomics, transcriptomics, proteomics and metabolomics) permitted the improvement on the knowledge in this field, by providing with a huge amount of information regarding the biological processes involved in reproductive success, thereby getting a broader view of complex biological systems with a relatively low cost and effort.

  5. Current status of truffle cultivation: recent results and future perspectives

    Directory of Open Access Journals (Sweden)

    Alessandra Zambonelli

    2015-12-01

    Full Text Available In this review the current status of truffle cultivation in Europe and outside Europe is reported. While the cultivation of Tuber melanosporum (Périgord black truffle, Tuber aestivum (summer or Burgundy truffle and Tuber borchii (bianchetto truffle gave good results, only the Italian white truffle (Tuber magnatum, which is the most expensive, has yet to be successfully cultivated. In future a revolutionary approach to truffle cultivation would be the application of mycelial inoculation techniques for producing Tuber infected plants which will allow to select the fungal strains adapted to specific climatic, edaphic conditions and hosts. The new insights which will be gained by the extensive Tuber genome sequencing programme will also help to improve truffle cultivation techniques.

  6. Current perspectives: the impact of cyberbullying on adolescent health.

    Science.gov (United States)

    Nixon, Charisse L

    2014-01-01

    Cyberbullying has become an international public health concern among adolescents, and as such, it deserves further study. This paper reviews the current literature related to the effects of cyberbullying on adolescent health across multiple studies worldwide and provides directions for future research. A review of the evidence suggests that cyberbullying poses a threat to adolescents' health and well-being. A plethora of correlational studies have demonstrated a cogent relationship between adolescents' involvement in cyberbullying and negative health indices. Adolescents who are targeted via cyberbullying report increased depressive affect, anxiety, loneliness, suicidal behavior, and somatic symptoms. Perpetrators of cyberbullying are more likely to report increased substance use, aggression, and delinquent behaviors. Mediating/moderating processes have been found to influence the relationship between cyberbullying and adolescent health. More longitudinal work is needed to increase our understanding of the effects of cyberbullying on adolescent health over time. Prevention and intervention efforts related to reducing cyberbullying and its associated harms are discussed.

  7. Quantum Dots in the Therapy: Current Trends and Perspectives.

    Science.gov (United States)

    Pohanka, Miroslav

    2017-01-01

    Quantum dots are an emerging nanomaterial with broad use in technical disciplines; however, their application in the field of biomedicine becomes also relevant and significant possibilities have appeared since the discovery in 1980s. The current review is focused on the therapeutic applications of quantum dots which become an emerging use of the particles. They are introduced as potent carriers of drugs and as a material well suited for the diagnosis of disparate pathologies like visualization of cancer cells or pathogenic microorganisms. Quantum dots toxicity and modifications for the toxicity reduction are discussed here as well. Survey of actual papers and patents in the field of quantum dots use in the biomedicine is provided. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. PRA: A PERSPECTIVE ON STRENGTHS, CURRENT LIMITATIONS, AND POSSIBLE IMPROVEMENTS

    Directory of Open Access Journals (Sweden)

    ALI MOSLEH

    2014-02-01

    Full Text Available Probabilistic risk assessment (PRA has been used in various technological fields to assist regulatory agencies, managerial decision makers, and systems designers in assessing and mitigating the risks inherent in these complex arrangements. Has PRA delivered on its promise? How do we gage PRA performance? Are our expectations about value of PRA realistic? Are there disparities between what we get and what we think we are getting form PRA and its various derivatives? Do current PRAs reflect the knowledge gained from actual events? How do we address potential gaps? These are some of the questions that have been raised over the years since the inception of the field more than forty years ago. This paper offers a brief assessment of PRA as a technical discipline in theory and practice, its key strengths and weaknesses, and suggestions on ways to address real and perceived shortcomings.

  9. Managing inflammatory bowel disease in pregnancy: current perspectives.

    Science.gov (United States)

    Pinder, Matthew; Lummis, Katie; Selinger, Christian P

    2016-01-01

    Inflammatory bowel disease (IBD) affects many women of childbearing age. The course of IBD is closely related to pregnancy outcomes with poorly controlled IBD increasing the risk of prematurity, low weight for gestation, and fetal loss. As such, women with IBD face complex decision making weighing the risks of active disease versus those of medical treatments. This review summarizes the current evidence regarding the safety and efficacy of IBD treatments during pregnancy and lactation aiming to provide up-to-date guidance for clinicians. Over 50% of women have poor IBD- and pregnancy-related knowledge, which is associated with views contrary to medical evidence and voluntary childlessness. This review highlights the effects of poor patient knowledge and critically evaluates interventions for improving patient knowledge and outcomes.

  10. Antiviral chemotherapy in veterinary medicine: current applications and perspectives.

    Science.gov (United States)

    Dal Pozzo, F; Thiry, E

    2014-12-01

    The current situation in the use of antiviral drugs in veterinary medicine is characterised by a novel and optimistic approach.Viruses of veterinary importance are still used as animal models in the developmentof human therapeutics, but there is growing interest in many of these viruses in the identification of antiviral molecules for use in both livestock and companion animals. The use of antiviral drugs in livestock animals is envisaged for the treatment or control of disease on a large scale (mass treatment), whereas in companion animals an individual approach is favoured. An overview of the most recent examples of research in the use of antivirals in veterinary medicine is presented, with particular emphasis on their in vivo applications.

  11. Chronic traumatic encephalopathy: historical origins and current perspective.

    Science.gov (United States)

    Montenigro, Philip H; Corp, Daniel T; Stein, Thor D; Cantu, Robert C; Stern, Robert A

    2015-01-01

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is most often identified in postmortem autopsies of individuals exposed to repetitive head impacts, such as boxers and football players. The neuropathology of CTE is characterized by the accumulation of hyperphosphorylated tau protein in a pattern that is unique from that of other neurodegenerative diseases, including Alzheimer's disease. The clinical features of CTE are often progressive, leading to dramatic changes in mood, behavior, and cognition, frequently resulting in debilitating dementia. In some cases, motor features, including parkinsonism, can also be present. In this review, the historical origins of CTE are revealed and an overview of the current state of knowledge of CTE is provided, including the neuropathology, clinical features, proposed clinical and pathological diagnostic criteria, potential in vivo biomarkers, known risk factors, and treatment options.

  12. Current perspectives: the impact of cyberbullying on adolescent health

    Science.gov (United States)

    Nixon, Charisse L

    2014-01-01

    Cyberbullying has become an international public health concern among adolescents, and as such, it deserves further study. This paper reviews the current literature related to the effects of cyberbullying on adolescent health across multiple studies worldwide and provides directions for future research. A review of the evidence suggests that cyberbullying poses a threat to adolescents’ health and well-being. A plethora of correlational studies have demonstrated a cogent relationship between adolescents’ involvement in cyberbullying and negative health indices. Adolescents who are targeted via cyberbullying report increased depressive affect, anxiety, loneliness, suicidal behavior, and somatic symptoms. Perpetrators of cyberbullying are more likely to report increased substance use, aggression, and delinquent behaviors. Mediating/moderating processes have been found to influence the relationship between cyberbullying and adolescent health. More longitudinal work is needed to increase our understanding of the effects of cyberbullying on adolescent health over time. Prevention and intervention efforts related to reducing cyberbullying and its associated harms are discussed. PMID:25177157

  13. Open problems and perspectives offered by current and future instruments

    Directory of Open Access Journals (Sweden)

    Gérin M.

    2012-01-01

    Full Text Available We summarize recent observational and theoretical results and discuss the open challenges for astrochemistry and the promises offered by the current and upcoming instruments. Some of the main challenges are listed below. Characterization of the structure of the interstellar medium Coupling of the matter with magnetic fields, role of cosmic rays Coupling of the dynamics with the evolution of matter (chemistry, ionization degree, depletion, desorption Characterization of dust grains (composition, size, emissivity, polarization Evolution of the carbonaceous matter, PAHs, aggregates and Diffuse Interstellar Bands (DIBs carriers Oxygen chemistry and the low abundance of molecular oxygen Nitrogen chemistry and its seeds, the nitrogen hydrides Sulfur chemistry and the contribution of S+ to the charge balance of translucent matter Neutral-neutral reactions involving simple radicals (CH, CH2, OH, etc..

  14. Emerging drugs of abuse: current perspectives on synthetic cannabinoids

    Directory of Open Access Journals (Sweden)

    Debruyne D

    2015-10-01

    Full Text Available Danièle Debruyne,1,2 Reynald Le Boisselier1 1Centre for Evaluation and Information on Pharmacodependence - Addictovigilance (CEIP-A, 2Toxicology and Pharmacology Laboratory, Department of Pharmacology, University Hospital Centre Côte de Nacre, Caen, France Abstract: New psychoactive drugs that have appeared over the last decade are typically dominated by cathinones and synthetic cannabinoids (SCs. SCs have been emerging as recreational drugs because they mimic the euphoria effect of cannabis while still being legal. Sprayed on natural herb mixtures, SCs have been primarily sold as “herbal smoking blends” or “herbal incense” under brand names like “Spice” or “K2”. Currently, SCs pure compounds are available from websites for the combination with herbal materials or for the use in e-cigarettes. For the past 5 years, an ever increasing number of compounds, representative of different chemical classes, have been promoted and now represent a large assortment of new popular drugs of abuse, which are difficult to properly identify. Their legal status varies by country with many government institutions currently pushing for their control. The in vitro binding to CB1/CB2 receptors is usually well-known and considerable differences have been found in the CB1 versus CB2 selectivity and potency within the different SCs, with several structure-activity relations being evident. Desired effects by CB1 agonist users are relaxation/recreative, however, cardiovascular, gastrointestinal, or psychiatric/neurological side effects are commonly reported. At present there is no specific antidote existing if an overdose of designer drugs was to occur, and no curative treatment has been approved by health authorities. Management of acute toxic effects is mainly symptomatic and extrapolated from experience with cannabis. Keywords: synthetic cannabinoids, chemistry, analysis, pharmacology, toxicology, dependence, medical care

  15. Mesenchymal stem cell therapy for osteoarthritis: current perspectives

    Directory of Open Access Journals (Sweden)

    Wyles CC

    2015-08-01

    Full Text Available Cody C Wyles,1 Matthew T Houdek,2 Atta Behfar,3 Rafael J Sierra,21Mayo Medical School, 2Department of Orthopedic Surgery, 3Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USAAbstract: Osteoarthritis (OA is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.Keywords: mesenchymal stem cell, osteoarthritis, treatment, regenerative medicine, cell therapy

  16. Orphan drugs in development for urea cycle disorders: current perspectives

    Directory of Open Access Journals (Sweden)

    Häberle J

    2014-09-01

    Full Text Available Johannes Häberle,1 Shawn E McCandless2 1Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland; 2Center for Human Genetics, University Hospitals Case Medical Center, and Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA Abstract: The urea cycle disorders are caused by deficiency of one of the six hepatic enzymes or two transporters involved in detoxification of ammonia. The resulting hyperammonemia causes severe brain injury unless aggressive steps are taken to reduce the accumulation of ammonia, which is thought to be the most toxic metabolite. This review describes the current state of chronic management of urea cycle disorders, focusing on new and emerging therapies. Management strategies include the mainstay of treatment, namely dietary protein restriction and supplementation with l-arginine or l-citrulline. Several currently approved medications utilize and enhance alternative pathways of waste nitrogen excretion (sodium benzoate, sodium phenylacetate, sodium phenylbutyrate in several formulations, and glycerol phenylbutyrate, working through conjugation of the drug to either glycine (in the case of benzoate or glutamine, the products of which are excreted in the urine. Carglumic acid activates the first committed step of conversion of ammonia to urea, carbamoylphosphate synthetase, and thus effectively treats defective synthesis of the endogenous activator, N-acetylglutamate, whether due to genetic defects or biochemical inhibition of the N-acetylglutamate synthase enzyme. Approaches to neuroprotection during episodes of hyperammonemia are discussed, including the use of controlled hypothermia (brain cooling, as well as proposed, but as yet untested, pharmacologic therapies. Finally, cell-based therapies, including liver transplantation, infusion of fresh or cryopreserved hepatocytes, use of stem cells, and new approaches to gene

  17. Current perspectives on antibody-mediated rejection after lung transplantation

    Directory of Open Access Journals (Sweden)

    Witt CA

    2014-10-01

    Full Text Available Chad A Witt, Ramsey R Hachem Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, Saint Louis, MO, USA Abstract: The role of donor-specific antibodies (DSA to human leukocyte antigens and the burden of antibody-mediated rejection (AMR in lung transplantation remain enigmatic. Over the past several years, evidence has been emerging that humoral immunity plays an important role in the development of both acute and chronic lung allograft dysfunction (CLAD. Multiple case reports and case series have identified lung allograft recipients with clinical findings consistent with acute AMR. However, there is currently no widely accepted definition for AMR in lung transplantation, and this has been a significant barrier to furthering our understanding of this form of rejection. Nonetheless, the development of DSA after transplantation has consistently been identified as an independent risk factor for persistent and high-grade acute cellular rejection and CLAD. This has raised the possibility that chronic AMR may be a distinct phenotype of CLAD although evidence supporting this paradigm is still lacking. Additionally, antibodies to lung-restricted self-antigens (collagen V and K-α 1 tubulin have been associated with primary graft dysfunction early and the development of CLAD late after transplantation, and emerging evidence underscores significant interactions between autoimmunity and alloimmunity after transplantation. There is currently an active International Society for Heart and Lung Transplantation working group that is developing an operational definition for AMR in lung transplantation. This will be critical to improve our understanding of this form of rejection and conduct clinical trials to identify optimal treatment strategies. This review will summarize the literature on DSA and AMR in lung transplantation and discuss the impact of antibodies to self-antigens on lung

  18. Current achievements and future perspectives of metronomic chemotherapy.

    Science.gov (United States)

    Romiti, Adriana; Falcone, Rosa; Roberto, Michela; Marchetti, Paolo

    2017-06-01

    In recent years, many anticancer drugs have been tested at metronomic dosages for a variety of tumours. Mechanisms of action attributed to metronomic chemotherapy (MCT) include antiangiogenesis, immunomodulation, direct inhibition of tumour growth, effect on tumour initiating cells and the modulation of clonal evolution. An active clinical research, aimed at testing MCT in several cancers, has been conducted over the past 15 years. However, because the majority of available results come from earlier phase II studies, mainly performed in the area of breast cancer (BC), it is clear that there are areas still to be investigated. We considered current studies dealing with MCT according to the clinical setting of patients. Despite a certain degree of overlap, we were able to identify four main clinical indications for MCT: refractory disease and frailty of patients, advanced stage disease (requiring first and second-line therapy), early stage disease and maintenance therapy after induction chemotherapy. In addition, a section of this review has been addressed to the combination of MCT with immunotherapy following the growing interest in the reinstatement of immune-surveillance. Crucial questions, such as the definition of optimal schedules of continuously delivered, low-dose chemotherapy and the recognition and validation of predictive biomarkers, need to be further addressed. Moreover, comparisons with the best supportive care are especially lacking and thus urgently awaited to establish the key role of MCT in the care of pretreated and frail patients. Maintenance therapy promises to be one of the most worthwhile developments for MCT. Currently, several combination strategies with standard chemotherapy, target agents or immunotherapy are under investigation but further efforts are needed to fill the gaps of knowledge in this field.

  19. Current and Perspective Applications of Dense Plasma Focus Devices

    Science.gov (United States)

    Gribkov, V. A.

    2008-04-01

    Dense Plasma Focus (DPF) devices' applications, which are intended to support the main-stream large-scale nuclear fusion programs (NFP) from one side (both in fundamental problems of Dense Magnetized Plasma physics and in its engineering issues) as well as elaborated for an immediate use in a number of fields from the other one, are described. In the first direction such problems as self-generated magnetic fields, implosion stability of plasma shells having a high aspect ratio, etc. are important for the Inertial Confinement Fusion (ICF) programs (e.g. as NIF), whereas different problems of current disruption phenomenon, plasma turbulence, mechanisms of generation of fast particles and neutrons in magnetized plasmas are of great interest for the large devices of the Magnetic Plasma Confinement—MPC (e.g. as ITER). In a sphere of the engineering problems of NFP it is shown that in particular the radiation material sciences have DPF as a very efficient tool for radiation tests of prospect materials and for improvement of their characteristics. In the field of broad-band current applications some results obtained in the fields of radiation material sciences, radiobiology, nuclear medicine, express Neutron Activation Analysis (including a single-shot interrogation of hidden illegal objects), dynamic non-destructive quality control, X-Ray microlithography and micromachining, and micro-radiography are presented. As the examples of the potential future applications it is proposed to use DPF as a powerful high-flux neutron source to generate very powerful pulses of neutrons in the nanosecond (ns) range of its duration for innovative experiments in nuclear physics, for the goals of radiation treatment of malignant tumors, for neutron tests of materials of the first wall, blankets and NFP device's constructions (with fluences up to 1 dpa per a year term), and ns pulses of fast electrons, neutrons and hard X-Rays for brachytherapy.

  20. Current perspectives in HIV post-exposure prophylaxis

    Directory of Open Access Journals (Sweden)

    Sultan B

    2014-10-01

    Full Text Available Binta Sultan,1,2 Paul Benn,1 Laura Waters1 1Department of Genitourinary Medicine, Mortimer Market Centre, Central and North West London NHS Foundation Trust, London, UK; 2Centre for Sexual Health and HIV Research, University College London, London, UK Abstract: The incidence of human immunodeficiency virus (HIV infection continues to rise among core groups and efforts to reduce the numbers of new infections are being redoubled. Post-exposure prophylaxis (PEP is the use of short-term antiretroviral therapy (ART to reduce the risk of acquisition of HIV infection following exposure. Current guidelines recommend a 28-day course of ART within 36–72 hours of exposure to HIV. As long as individuals continue to be exposed to HIV there will be a role for PEP in the foreseeable future. Nonoccupational PEP, the vast majority of which is for sexual exposure (PEPSE, has a significant role to play in HIV prevention efforts. Awareness of PEP and its availability for both clinicians and those who are eligible to receive it are crucial to ensure that PEP is used to its full potential in any HIV prevention strategy. In this review, we provide current evidence for the use of PEPSE, assessment of the risk of HIV transmission, indications for PEP, drug regimens, and management of patients started on PEP. We summarize national and international guidelines for the use of PEPSE. We explore the place of PEP within the wider strategy of reducing HIV incidence rates in the era of treatment as prevention and pre-exposure prophylaxis. We also consider the implications of recent data from interventional and observational studies demonstrating significant reductions in the risk of HIV transmission within a serodiscordant relationship if the HIV-positive partner is taking effective ART upon PEP guidelines. Keywords: post-exposure prophylaxis, pre-exposure prophylaxis, treatment as prevention, human immunodeficiency virus

  1. Heparanase activates the syndecan-syntenin-ALIX exosome pathway.

    Science.gov (United States)

    Roucourt, Bart; Meeussen, Sofie; Bao, Jie; Zimmermann, Pascale; David, Guido

    2015-04-01

    Exosomes are secreted vesicles of endosomal origin involved in signaling processes. We recently showed that the syndecan heparan sulfate proteoglycans control the biogenesis of exosomes through their interaction with syntenin-1 and the endosomal-sorting complex required for transport accessory component ALIX. Here we investigated the role of heparanase, the only mammalian enzyme able to cleave heparan sulfate internally, in the syndecan-syntenin-ALIX exosome biogenesis pathway. We show that heparanase stimulates the exosomal secretion of syntenin-1, syndecan and certain other exosomal cargo, such as CD63, in a concentration-dependent manner. In contrast, exosomal CD9, CD81 and flotillin-1 are not affected. Conversely, reduction of endogenous heparanase reduces the secretion of syntenin-1-containing exosomes. The ability of heparanase to stimulate exosome production depends on syntenin-1 and ALIX. Syndecans, but not glypicans, support exosome biogenesis in heparanase-exposed cells. Finally, heparanase stimulates intraluminal budding of syndecan and syntenin-1 in endosomes, depending on the syntenin-ALIX interaction. Taken together, our findings identify heparanase as a modulator of the syndecan-syntenin-ALIX pathway, fostering endosomal membrane budding and the biogenesis of exosomes by trimming the heparan sulfate chains on syndecans. In addition, our data suggest that this mechanism controls the selection of specific cargo to exosomes.

  2. Epidermal Growth Factor Receptor in Prostate Cancer Derived Exosomes.

    Directory of Open Access Journals (Sweden)

    Geetanjali Kharmate

    Full Text Available Exosomes proteins and microRNAs have gained much attention as diagnostic tools and biomarker potential in various malignancies including prostate cancer (PCa. However, the role of exosomes and membrane-associated receptors, particularly epidermal growth factor receptor (EGFR as mediators of cell proliferation and invasion in PCa progression remains unexplored. EGFR is frequently overexpressed and has been associated with aggressive forms of PCa. While PCa cells and tissues express EGFR, it is unknown whether exosomes derived from PCa cells or PCa patient serum contains EGFR. The aim of this study was to detect and characterize EGFR in exosomes derived from PCa cells, LNCaP xenograft and PCa patient serum. Exosomes were isolated from conditioned media of different PCa cell lines; LNCaP xenograft serum as well as patient plasma/serum by differential centrifugation and ultracentrifugation on a sucrose density gradient. Exosomes were confirmed by electron microscopy, expression of exosomal markers and NanoSight™ analysis. EGFR expression was determined by western blot analysis and ELISA. This study demonstrates that exosomes may easily be derived from PCa cell lines, serum obtained from PCa xenograft bearing mice and clinical samples derived from PCa patients. Presence of exosomal EGFR in PCa patient exosomes may present a novel approach for measuring of the disease state. Our work will allow to build on this finding for future understanding of PCa exosomes and their potential role in PCa progression and as minimal invasive biomarkers for PCa.

  3. Pseudotyping exosomes for enhanced protein delivery in mammalian cells.

    Science.gov (United States)

    Meyer, Conary; Losacco, Joseph; Stickney, Zachary; Li, Lingxuan; Marriott, Gerard; Lu, Biao

    2017-01-01

    Exosomes are cell-derived nanovesicles that hold promise as living vehicles for intracellular delivery of therapeutics to mammalian cells. This potential, however, is undermined by the lack of effective methods to load exosomes with therapeutic proteins and to facilitate their uptake by target cells. Here, we demonstrate how a vesicular stomatitis virus glycoprotein (VSVG) can both load protein cargo onto exosomes and increase their delivery ability via a pseudotyping mechanism. By fusing a set of fluorescent and luminescent reporters with VSVG, we show the successful targeting and incorporation of VSVG fusions into exosomes by gene transfection and fluorescence tracking. We subsequently validate our system by live cell imaging of VSVG and its participation in endosomes/exosomes that are ultimately released from transfected HEK293 cells. We show that VSVG pseudotyping of exosomes does not affect the size or distributions of the exosomes, and both the full-length VSVG and the VSVG without the ectodomain are shown to integrate into the exosomal membrane, suggesting that the ectodomain is not required for protein loading. Finally, exosomes pseudotyped with full-length VSVG are internalized by multiple-recipient cell types to a greater degree compared to exosomes loaded with VSVG without the ectodomain, confirming a role of the ectodomain in cell tropism. In summary, our work introduces a new genetically encoded pseudotyping platform to load and enhance the intracellular delivery of therapeutic proteins via exosome-based vehicles to target cells.

  4. The biology and function of exosomes in cancer

    Science.gov (United States)

    Kalluri, Raghu

    2016-01-01

    Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40–150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathways in cells they fuse or interact with. Exosomes are detected in the tumor microenvironment, and emerging evidence suggests that they play a role in facilitating tumorigenesis by regulating angiogenesis, immunity, and metastasis. Circulating exosomes can be used as liquid biopsies and noninvasive biomarkers for early detection, diagnosis, and treatment of cancer patients. PMID:27035812

  5. Using exosomes, naturally-equipped nanocarriers, for drug delivery

    Science.gov (United States)

    Batrakova, Elena V.; Kim, Myung Soo

    2015-01-01

    Exosomes offer distinct advantages that uniquely position them as highly effective drug carriers. Comprised of cellular membranes with multiple adhesive proteins on their surface, exosomes are known to specialize in cell–cell communications and provide an exclusive approach for the delivery of various therapeutic agents to target cells. In addition, exosomes can be amended through their parental cells to express a targeting moiety on their surface, or supplemented with desired biological activity. Development and validation of exosome-based drug delivery systems are the focus of this review. Different techniques of exosome isolation, characterization, drug loading, and applications in experimental disease models and clinic are discussed. Exosome-based drug formulations may be applied to a wide variety of disorders such as cancer, various infectious, cardiovascular, and neuro-degenerative disorders. Overall, exosomes combine benefits of both synthetic nanocarriers and cell-mediated drug delivery systems while avoiding their limitations. PMID:26241750

  6. Current Perspectives on Desmoid Tumors: The Mayo Clinic Approach

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    Scott Okuno

    2011-08-01

    Full Text Available Desmoid tumors are a rare group of locally aggressive, non malignant tumors of fibroblastic origin that can lead to significant morbidity due to local invasion. Despite advances in the understanding of these tumors, their natural history is incompletely understood and the optimal treatment is still a matter of debate. Local control is the main goal of treatment and there has been a change in philosophy regarding the management of these tumors from aggressive surgical resection to function preservation. A multidisciplinary approach is essential to plan local control with acceptable morbidity. The current Mayo Clinic algorithm for the treatment of these tumors is based on institutional experience and the available evidence in the literature: asymptomatic/non progressive lesions away from vital structures are managed with observation and regular imaging; primary or recurrent desmoid tumors which are symptomatic or progressive or near vital structures are managed with wide surgical resection when wide surgical margins are possible with minimal functional and cosmetic loss. When positive or close surgical margins are likely, surgical resection with adjuvant radiotherapy or definitive radiotherapy is preferred. If likely functional or cosmetic deficit is unacceptable, radiotherapy is the treatment of choice. Unresectable lesions are considered for radiotherapy, chemotherapy or newer modalities however an unresectable lesion associated with a painful, functionless, infected extremity is managed with an amputation.

  7. Current Perspectives on Profiling and Enhancing Wheelchair Court Sport Performance.

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    Paulson, Thomas; Goosey-Tolfrey, Victoria

    2017-03-01

    Despite the growing interest in Paralympic sport, the evidence base for supporting elite wheelchair sport performance remains in its infancy when compared with able-bodied (AB) sport. Subsequently, current practice is often based on theory adapted from AB guidelines, with a heavy reliance on anecdotal evidence and practitioner experience. Many principles in training prescription and performance monitoring with wheelchair athletes are directly transferable from AB practice, including the periodization and tapering of athlete loads around competition, yet considerations for the physiological consequences of an athlete's impairment and the interface between athlete and equipment are vital when targeting interventions to optimize in-competition performance. Researchers and practitioners are faced with the challenge of identifying and implementing reliable protocols that detect small but meaningful changes in impairment-specific physical capacities and on-court performance. Technologies to profile both linear and rotational on-court performance are an essential component of sport-science support to understand sport-specific movement profiles and prescribe training intensities. In addition, an individualized approach to the prescription of athlete training and optimization of the "wheelchair-user interface" is required, accounting for an athlete's anthropometrics, sports classification, and positional role on court. In addition to enhancing physical capacities, interventions must focus on the integration of the athlete and his or her equipment, as well as techniques for limiting environmental influence on performance. Taken together, the optimization of wheelchair sport performance requires a multidisciplinary approach based on the individual requirements of each athlete.

  8. Chemopreventive opportunities to control basal cell carcinoma: Current perspectives.

    Science.gov (United States)

    Tilley, Cynthia; Deep, Gagan; Agarwal, Rajesh

    2015-09-01

    Basal cell carcinoma (BCC) is a major health problem with approximately 2.8 million new cases diagnosed each year in the United States. BCC incidences have continued to rise due to lack of effective chemopreventive options. One of the key molecular characteristics of BCC is the sustained activation of hedgehog signaling through inactivating mutations in the tumor suppressor gene patch (Ptch) or activating mutations in Smoothened. In the past, several studies have addressed targeting the activated hedgehog pathway for the treatment and prevention of BCC, although with toxic effects. Other studies have attempted BCC chemoprevention through targeting the promotional phase of the disease especially the inflammatory component. The compounds that have been utilized in pre-clinical and/or clinical studies include green and black tea, difluoromethylornithine, thymidine dinucleotide, retinoids, non-steroidal anti-inflammatory drugs, vitamin D3, and silibinin. In this review, we have discussed genetic and epigenetic modifications that occur during BCC development as well as the current state of BCC pre-clinical and clinical chemoprevention studies. © 2015 Wiley Periodicals, Inc.

  9. Clinical proteomics: Current status, challenges, and future perspectives

    Directory of Open Access Journals (Sweden)

    Shyh-Horng Chiou

    2011-01-01

    Full Text Available This account will give an overview and evaluation of the current advances in mass spectrometry (MS-based proteomics platforms and technology. A general review of some background information concerning the application of these methods in the characterization of molecular sizes and related protein expression profiles associated with different types of cells under varied experimental conditions will be presented. It is intended to provide a concise and succinct overview to those clinical researchers first exposed to this foremost powerful methodology in modern life sciences of postgenomic era. Proteomic characterization using highly sophisticated and expensive instrumentation of MS has been used to characterize biological samples of complex protein mixtures with vastly different protein structure and composition. These systems are then used to highlight the versatility and potential of the MS-based proteomic strategies for facilitating protein expression analysis of various disease-related organisms or tissues of interest. Major MS-based strategies reviewed herein include (1 matrix-assisted laser desorption ionization-MS and electron-spray ionization proteomics; (2 one-dimensional or two-dimensional gel-based proteomics; (3 gel-free shotgun proteomics in conjunction with liquid chromatography/tandem MS; (4 Multiple reaction monitoring coupled tandem MS quantitative proteomics and; (5 Phosphoproteomics based on immobilized metal affinity chromatography and liquid chromatography-MS/MS.

  10. Hypertension in Latin America: Current perspectives on trends and characteristics.

    Science.gov (United States)

    Ruilope, L M; Chagas, A C P; Brandão, A A; Gómez-Berroterán, R; Alcalá, J J A; Paris, J V; Cerda, J J O

    The region of Latin America, which includes Central America, the Caribbean and South America, is one that is rapidly developing. Signified by socio-economic growth, transition and development over the last few decades, living standards in countries like Brazil and Mexico have improved dramatically, including improvements in education and health care. An important marker of socio-economic change has been the epidemiological shift in disease burden. Cardiovascular disease is now the leading cause of death in Latin America, and the drop in prevalence of infectious diseases has been accompanied by a rise in non-communicable diseases. Hypertension is the major risk factor driving the cardiovascular disease continuum. In this article we aim to discuss the epidemiological and management trends and patterns in hypertension that may be specific or more common to Latin-American populations - what we term 'Latin American characteristics' of hypertension - via a review of the recent literature. Recognizing that there may be a specific profile of hypertension for Latin-American patients may help to improve their treatment, with the ultimate goal to reduce their cardiovascular risk. We focus somewhat on the countries of Brazil, Mexico and Venezuela, the experience of which may reflect other Latin American countries that currently have less published data regarding epidemiology and management practices. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Robotic single port cholecystectomy: current data and future perspectives.

    Science.gov (United States)

    Angelou, Anastasios; Skarmoutsos, Athanasios; Margonis, Georgios A; Moris, Demetrios; Tsigris, Christos; Pikoulis, Emmanouil

    2017-04-01

    Minimally invasive techniques are used more and more frequently. Since conventional laparoscopic approach has been the gold standard, surgeons in their effort to further reduce the invasiveness of conventional laparoscopic cholecystectomy have adopted Single Incision approach. The widespread adoption of robotics has led to the inevitable hybridization of robotic technology with laparoendoscopic single-site surgery (LESS). As a result, employment of the da Vinci surgical system may allow greater surgical maneuverability, improving ergonomics. A review of the English literature was conducted to evaluate all robotic single port cholecystectomy performed till today. Demographic data, operative parameters, postoperative outcomes and materials used for the operation were collected and assessed. A total of 12 studies, including 501 patients were analyzed. Demographics and clinical characteristics of the patients was heterogeneous, but in most studies a mean BMI Robotic single port cholecystectomy is a safe and feasible alternative to conventional multiport laparoscopic or manual robotic approach. However, current data do not suggest a superiority of robotic SILC over other established methods.

  12. Robot-assisted urological surgery: Current status and future perspectives.

    Science.gov (United States)

    Ghani, Khurshid R; Trinh, Quoc-Dien; Sammon, Jesse; Jeong, Wooju; Dabaja, Ali; Menon, Mani

    2012-03-01

    To discuss the current status of robot-assisted urological surgery. We searched PubMed for articles published from 2008 using the search terms 'advances', 'robotic surgery equipment' and 'instrumentation'. We also searched PubMed for articles describing the latest developments in reconstructive techniques for lower and upper urinary tract procedures. Finally, we searched PubMed for original articles containing the terms 'robotic surgery training' and 'credentialing'. With each release of hardware or ancillary instrumentation, the reconstructive abilities of the da Vinci surgical system (Intuitive Surgical, Sunnyvale, CA, USA) improve. Recent developments in reconstructive capabilities of robotic urological surgery include posterior reconstruction during robot-assisted radical prostatectomy, barbed sutures for urethrovesical anastomosis, sliding-clip renorrhaphy for robot-assisted partial nephrectomy, and repair of pelvic organ prolapse. The safe implementation of robotic surgery is aided by new guidelines in credentialing and proctoring, and the introduction of virtual reality simulators for training. Robotic urological surgery is rapidly developing and expanding globally. To achieve the highest levels of safety for patients, surgeons must ensure that the implementation of robotic surgery is an integrative and effective process.

  13. Early Modern Consumption History: Current Challenges and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Wouter Ryckbosch

    2015-03-01

    Full Text Available Stimulated by wide-ranging theories on its cultural and economic significance, the history of early modern consumption in the Low Countries has received a remarkable amount of attention in historiography during the last three decades. During this period the growing body of empirical evidence, as well as shifting theoretical frameworks, have gradually altered our understanding of early modern patterns of consumption, their causes and consequences. The current article presents a review of the main tendencies in the field of early modern consumption history, and the challenges to this historiographical field these have presented. Based on these challenges, the article suggests new avenues for future research. Vroegmoderne consumptiegeschiedenis. Hedendaagse uitdagingen entoekomstperspectievenGestimuleerd door verstrekkende nieuwe theorieën over haar cultureleen economische betekenis, heeft de historiografie met betrekking totvroegmoderne consumptie in de Nederlanden op opmerkelijk veel aandacht mogen rekenen tijdens de voorbije drie decennia. Daarbij hebben zowel een groeiende beschikbaarheid van empirisch bronnenmateriaal, als verschuivende theoretische perspectieven,  geleidelijk aan ons begrip van vroegmoderne consumptiepatronen, en hun oorzaken en gevolgen grondig veranderd. Het huidige artikel biedt een overzicht van de belangrijkste tendensen in het domein van de vroegmoderne consumptiegeschiedenis, gevolgd door nieuwe uitdagingen en toekomstperspectieven.

  14. Preoperative management of children with esophageal atresia: current perspectives

    Directory of Open Access Journals (Sweden)

    Parolini F

    2017-01-01

    Full Text Available Filippo Parolini,1 Anna Lavinia Bulotta,1 Sonia Battaglia,1 Daniele Alberti1,2 1Department of Pediatric Surgery, “Spedali Civili” Children’s Hospital, 2Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy Abstract: Esophageal atresia remains one of the most challenging congenital anomalies of the newborn. In recent years, because of the advances in prenatal diagnosis, neonatal critical care, and surgical procedures, overall outcomes have improved substantially, including for premature children. Nowadays, most of the research is focused on medium- and long-term morbidity, with particular reference to respiratory and gastroesophageal problems; the high frequency of late sequelae in esophageal atresia warrants regular and multidisciplinary checkups throughout adulthood. Surprisingly, there are few studies on the impact of prenatal diagnosis and there is continuing debate over the prenatal and preoperative management of these complex patients. In this review, we analyze the literature surrounding current knowledge on the management of newborns affected by esophageal atresia, focusing on prenatal management and preoperative assessment. Keywords: prenatal diagnosis, esophageal atresia, tracheoesophageal fistula, ultrasound scan, tracheobronchoscopy

  15. Complications and challenges associated with polycystic ovary syndrome: current perspectives

    Science.gov (United States)

    Palomba, Stefano; Santagni, Susanna; Falbo, Angela; La Sala, Giovanni Battista

    2015-01-01

    Polycystic ovary syndrome (PCOS) represents the most common endocrine dysfunction in fertile women and it is considered a heterogeneous and multifaceted disorder, with multiple reproductive and metabolic phenotypes which differently affect the early- and long-term syndrome’s risks. Women with PCOS present an adverse reproductive profile, including a high risk of pregnancy-induced hypertension, preeclampsia, and gestational diabetes mellitus. Patients with PCOS present not only a higher prevalence of classic cardiovascular risk factors, such as hypertension, dyslipidemia, and type-2 diabetes mellitus, but also of nonclassic cardiovascular risk factors, including mood disorders, such as depression and anxiety. Moreover, at the moment, clinical data on cardiovascular morbidity and mortality in women with PCOS are controversial. Finally, women with PCOS show an increased risk of endometrial cancer compared to non-PCOS healthy women, particularly during premenopausal period. Currently, we are unable to clarify if the increased PCOS early- and long-term risks are totally due to PCOS per se or mostly due to obesity, in particular visceral obesity, that characterized the majority of PCOS patients. In any case, the main endocrine and gynecological scientific societies agree to consider women with PCOS at increased risk of obstetric, cardiometabolic, oncology, and psychological complications throughout life, and it is recommended that these women be accurately assessed with periodic follow-up. PMID:26261426

  16. Managing inflammatory bowel disease in pregnancy: current perspectives

    Directory of Open Access Journals (Sweden)

    Pinder M

    2016-10-01

    Full Text Available Matthew Pinder,1 Katie Lummis,1 Christian P Selinger1,2 1Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, 2University of Leeds, Leeds, UK Abstract: Inflammatory bowel disease (IBD affects many women of childbearing age. The course of IBD is closely related to pregnancy outcomes with poorly controlled IBD increasing the risk of prematurity, low weight for gestation, and fetal loss. As such, women with IBD face complex decision making weighing the risks of active disease versus those of medical treatments. This review summarizes the current evidence regarding the safety and efficacy of IBD treatments during pregnancy and lactation aiming to provide up-to-date guidance for clinicians. Over 50% of women have poor IBD- and pregnancy-related knowledge, which is associated with views contrary to medical evidence and voluntary childlessness. This review highlights the effects of poor patient knowledge and critically evaluates interventions for improving patient knowledge and outcomes. Keywords: pregnancy, breast feeding, nursing, inflammatory bowel disease, Crohn’s disease, ulcerative colitis

  17. Desalination and sustainability - An appraisal and current perspective.

    Science.gov (United States)

    Gude, Veera Gnaneswar

    2016-02-01

    Desalination technologies have evolved and advanced rapidly along with increasing water demands around the world since 1950s. Many reviews have focused on the techno-economic and environmental and ecological issues of the desalination technologies and emphasized the feasibility of desalination industry as an alternative to meet the water demands in many water scarce regions. Despite these efforts, many perceptions about desalination processes hinder their applications for potential water supplies. This article has two specific aims: 1) provide an overview of the desalination trends around the world and discuss the sustainability components of desalination processes in comparison with other water supply alternatives; and 2) discuss case studies for desalination, and drivers and factors that influence sustainable desalination and other alternative water sources for desalination to increase our current understanding on the sensitive and futuristic issues of water supply and resource management options for drought facing regions. Although some of the facts and recent developments discussed here show that desalination can be affordable and potentially sustainable, contributions that meaningfully address socio-economic and ecological and environmental issues of desalination processes are urgently required in this critical era of severe water stress for the present context and the future development of desalination technologies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. The role of simulation in teaching pediatric resuscitation: current perspectives

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    Lin Y

    2015-03-01

    Full Text Available Yiqun Lin,1 Adam Cheng2 1KidSIM-ASPIRE Simulation Research Program, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada; 2KidSIM-ASPIRE Research Program, Department of Pediatrics, Division of Emergency Medicine, University of Calgary, Alberta Children's Hospital, Calgary, AB, Canada Abstract: The use of simulation for teaching the knowledge, skills, and behaviors necessary for effective pediatric resuscitation has seen widespread growth and adoption across pediatric institutions. In this paper, we describe the application of simulation in pediatric resuscitation training and review the evidence for the use of simulation in neonatal resuscitation, pediatric advanced life support, procedural skills training, and crisis resource management training. We also highlight studies supporting several key instructional design elements that enhance learning, including the use of high-fidelity simulation, distributed practice, deliberate practice, feedback, and debriefing. Simulation-based training is an effective modality for teaching pediatric resuscitation concepts. Current literature has revealed some research gaps in simulation-based education, which could indicate the direction for the future of pediatric resuscitation research. Keywords: simulation, pediatric resuscitation, medical education, instructional design, crisis resource management, health care

  19. Pain in Neurodegenerative Disease: Current Knowledge and Future Perspectives

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    Marina de Tommaso

    2016-01-01

    Full Text Available Neurodegenerative diseases are going to increase as the life expectancy is getting longer. The management of neurodegenerative diseases such as Alzheimer’s disease (AD and other dementias, Parkinson’s disease (PD and PD related disorders, motor neuron diseases (MND, Huntington’s disease (HD, spinocerebellar ataxia (SCA, and spinal muscular atrophy (SMA, is mainly addressed to motor and cognitive impairment, with special care to vital functions as breathing and feeding. Many of these patients complain of painful symptoms though their origin is variable, and their presence is frequently not considered in the treatment guidelines, leaving their management to the decision of the clinicians alone. However, studies focusing on pain frequency in such disorders suggest a high prevalence of pain in selected populations from 38 to 75% in AD, 40% to 86% in PD, and 19 to 85% in MND. The methods of pain assessment vary between studies so the type of pain has been rarely reported. However, a prevalent nonneuropathic origin of pain emerged for MND and PD. In AD, no data on pain features are available. No controlled therapeutic trials and guidelines are currently available. Given the relevance of pain in neurodegenerative disorders, the comprehensive understanding of mechanisms and predisposing factors, the application and validation of specific scales, and new specific therapeutic trials are needed.

  20. Current perspectives: the impact of cyberbullying on adolescent health

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    Nixon CL

    2014-08-01

    Full Text Available Charisse L Nixon Pennsylvania State University, the Behrend College, Erie, PA, USA Abstract: Cyberbullying has become an international public health concern among adolescents, and as such, it deserves further study. This paper reviews the current literature related to the effects of cyberbullying on adolescent health across multiple studies worldwide and provides directions for future research. A review of the evidence suggests that cyberbullying poses a threat to adolescents' health and well-being. A plethora of correlational studies have demonstrated a cogent relationship between adolescents' involvement in cyberbullying and negative health indices. Adolescents who are targeted via cyberbullying report increased depressive affect, anxiety, loneliness, suicidal behavior, and somatic symptoms. Perpetrators of cyberbullying are more likely to report increased substance use, aggression, and delinquent behaviors. Mediating/moderating processes have been found to influence the relationship between cyberbullying and adolescent health. More longitudinal work is needed to increase our understanding of the effects of cyberbullying on adolescent health over time. Prevention and intervention efforts related to reducing cyberbullying and its associated harms are discussed. Keywords: cyberbullying, adolescent health, prevention, intervention

  1. Trypanocidal activity of nitroaromatic prodrugs: current treatments and future perspectives.

    Science.gov (United States)

    Wilkinson, Shane R; Bot, Christopher; Kelly, John M; Hall, Belinda S

    2011-01-01

    Chagas disease and African sleeping sickness are trypanosomal infections that represent important public health problems in Latin America and Africa, respectively. The restriction of these diseases to the poorer parts of the world has meant that they have been largely neglected and limited progress has been made in their treatment. The nitroheterocyclic prodrugs nifurtimox and benznidazole, in use against Chagas disease for >40 years, remain the only agents available for this infection. In the case of African sleeping sickness, nifurtimox has recently been added to the arsenal of medicines, with the nitroheterocycle fexinidazole currently under evaluation. For a long time, the cytotoxic mechanism of these drugs was poorly understood: nifurtimox was thought to act via production of superoxide anions and nitro radicals, while the mode of benznidazole action was more obscure. The trypanocidal activity of nitroheterocyclic drugs is now known to depend on a parasite type I nitroreductase (NTR). This enzyme is absent from mammalian cells, a difference that forms the basis for the drug selectivity. The role of this enzyme in drug activation has been genetically and biochemically validated. It catalyses the 2-electron reduction of nitroheterocyclic compounds within the parasite, producing toxic metabolites without significant generation of superoxide. Recognition that this enzyme is responsible for activation of nitroheterocyclic prodrugs has allowed screening for compounds that preferentially target the parasite. This approach has led to the identification of two new classes of anti-trypanosomal agents, nitrobenzylphosphoramide mustards and aziridinyl nitrobenzamides, and promises to yield new, safer, more effective drugs.

  2. Malt-induced premature yeast flocculation: current perspectives.

    Science.gov (United States)

    Panteloglou, Apostolos G; Smart, Katherine A; Cook, David J

    2012-06-01

    Premature yeast flocculation (PYF) is a sporadic problem for the malting and brewing industries which can have significant financial and logistical implications. The condition is characterised by abnormally heavy (and sometimes early) flocculation of yeast during brewery fermentations. The resulting low suspended yeast cell counts towards the end of the fermentation can result in flavour defects and incomplete attenuation (fermentation of sugars to alcohol). Despite several decades of research into the phenomenon, its precise nature and mechanisms have not been fully elucidated. In part this is because the term PYF has become a 'catch-all' syndrome which can have multiple origins. Furthermore, there are complex interactions in the malting and brewing processes which together mean that the PYF status of a malt sample is hard to predict at a generic level. Whether or not PYF is observed depends not only on barley quality, but on process factors in the maltings and to a substantial extent on the brewing yeast strain concerned. This article highlights the significance of PYF, and reviews current knowledge relating to the origins of this complex phenomenon.

  3. The relationship between oestrogen and muscle strength: a current perspective

    Directory of Open Access Journals (Sweden)

    Kirsty Jayne Elliott-Sale

    2014-04-01

    Full Text Available The relationship between muscle strength and oestrogen is ambiguous and is still largely unresolved. The evidence for and against an effect of oestradiol on determinants of muscle function is equivocal and often contradictory. The bulk of the research in this area was performed during the eighties and nineties, using models of reproductive functioning such as; the menstrual cycle, the menopause and hormone replacement therapy, oral contraceptives and in vitro fertilisation treatment, to alter the female hormonal milieu. In the last decade, approximately 15 papers have demonstrated a relationship, both positive and negative, between the concentration of oestrogen and skeletal muscle strength. Conversely, around 20 articles have not shown any influence of oestrogen on a number of strength measures. The majority of these studies were performed using post-menopausal and eumenorrheic females. Most current studies use hormonal assays to confirm oestrogen status, however no recent studies have reported the bioavailable concentration of oestradiol. Similarly, no research in the last 10 years has used in vitro fertilisation treatment or pregnancy as acute and chronic models of supra-physiological changes in sex hormone concentration. Future work should focus on performing meta-analyses on each of the key components of muscle strength in an attempt to elucidate a causal relationship. In addition, models of reproductive functioning that cause the greatest magnitude of change to oestrogen concentration should be used, while controlling as many confounding factors as possible.

  4. Alternatives to animal testing: current status and future perspectives.

    Science.gov (United States)

    Liebsch, Manfred; Grune, Barbara; Seiler, Andrea; Butzke, Daniel; Oelgeschläger, Michael; Pirow, Ralph; Adler, Sarah; Riebeling, Christian; Luch, Andreas

    2011-08-01

    On the occasion of the 20th anniversary of the Center for Alternative Methods to Animal Experiments (ZEBET), an international symposium was held at the German Federal Institute for Risk Assessment (BfR) in Berlin. At the same time, this symposium was meant to celebrate the 50th anniversary of the publication of the book "The Principles of Humane Experimental Technique" by Russell and Burch in 1959 in which the 3Rs principle (that is, Replacement, Reduction, and Refinement) has been coined and introduced to foster the development of alternative methods to animal testing. Another topic addressed by the symposium was the new vision on "Toxicology in the twenty-first Century", as proposed by the US-National Research Council, which aims at using human cells and tissues for toxicity testing in vitro rather than live animals. An overview of the achievements and current tasks, as well as a vision of the future to be addressed by ZEBET@BfR in the years to come is outlined in the present paper.

  5. Diagnosis and management of microscopic colitis: current perspectives

    Science.gov (United States)

    Bohr, Johan; Wickbom, Anna; Hegedus, Agnes; Nyhlin, Nils; Hultgren Hörnquist, Elisabeth; Tysk, Curt

    2014-01-01

    Collagenous colitis and lymphocytic colitis, together constituting microscopic colitis, are common causes of chronic diarrhea. They are characterized clinically by chronic nonbloody diarrhea and a macroscopically normal colonic mucosa where characteristic histopathological findings are seen. Previously considered rare, they now have emerged as common disorders that need to be considered in the investigation of the patient with chronic diarrhea. The annual incidence of each disorder is five to ten per 100,000 inhabitants, with a peak incidence in 60- to 70-year-old individuals and a predominance of female patients in collagenous colitis. The etiology and pathophysiology are not well understood, and the current view suggests an uncontrolled mucosal immune reaction to various luminal agents in predisposed individuals. Clinical symptoms comprise chronic diarrhea, abdominal pain, fatigue, weight loss, and fecal incontinence that may impair the patient’s health-related quality of life. An association is reported with other autoimmune disorders, such as celiac disease, thyroid disorders, diabetes mellitus, and arthritis. The best-documented treatment, both short-term and long-term, is budesonide, which induces clinical remission in up to 80% of patients after 8 weeks’ treatment. However, after successful budesonide therapy is ended, recurrence of clinical symptoms is common, and the best possible long-term management deserves further study. The long-term prognosis is good, and the risk of complications, including colonic cancer, is low. We present an update of the epidemiology, pathogenesis, diagnosis, and management of microscopic colitis. PMID:25170275

  6. FOG COMPUTING PERSPECTIVES IN CONNECTION WITH THE CURRENT GEOSPATIAL STANDARDS

    Directory of Open Access Journals (Sweden)

    E. Panidi

    2017-11-01

    Full Text Available Cloud Computing technologies and cloud-based Geographic Information Systems have became widely used in recent decades. However, the complexity and size of geospatial datasets remains growing and sometimes become going out of the cloud infrastructure paradigm. Additionally, many of currently used client devices have sufficient computational resources to store and process some amounts of data directly. Consequently, multilevel management techniques are demanded that support capabilities of horizontal (client-to-client data flows in addition to vertical (cloud-to-client data flows. These tendencies in information technologies (in general have led to the appearance of Fog Computing paradigm that extends a cloud infrastructure with the computational resources of client devices and implements client-side data storage, management and interchange. This position paper summarizes and discusses mentioned tendencies in connection with a number of available Open Geospatial Consortium standards. The paper highlights the standards, which can be recognized as the platform for the Fog Computing implementation into geospatial domain, and analyzing their strong and weak features from the Fog Computing point of view. The analysis is built upon author’s experience in implementation of the client-side geospatial Web services.

  7. Personalized medicine in CLL: Current status and future perspectives

    Science.gov (United States)

    Rozovski, Uri; Hazan-Halevy, Inbal; Keating, Michael J.; Estrov, Zeev

    2013-01-01

    Chronic lymphocytic leukemia (CLL) is the most common hematologic malignancy in the Western Hemisphere. Despite advances in research and the development of effective treatment regimens, CLL is still largely an incurable disease. Although several prognostic factors have been identified in recent years, most of the new prognostic factors are not utilized, and treatment decisions are still based on clinical staging and limited use of cytogenetic analysis. Patients with advanced disease are treated at diagnosis, whereas others, regardless of their prognostic indicators, are offered treatment only at disease progression. Furthermore, treatment guidelines for elderly or “unfit” patients are unavailable because most CLL trials have included mostly younger, healthier patients. Given the heterogeneity of the clinical manifestations and prognosis of CLL, patients are likely to benefit from a personalized therapeutic approach. Recent advances in CLL pathobiology research, the use of high-throughput technologies, and most importantly, the introduction of novel targeted therapies with high efficacy and low toxicity are currently transforming the treatment of CLL. A personalized approach that includes early intervention in selected patients with CLL is likely to bring physicians closer to the goal of attaining cures in most patients with CLL. PMID:23879961

  8. Neuroprotection for Stroke: Current Status and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Christoph Kleinschnitz

    2012-09-01

    Full Text Available Neuroprotection aims to prevent salvageable neurons from dying. Despite showing efficacy in experimental stroke studies, the concept of neuroprotection has failed in clinical trials. Reasons for the translational difficulties include a lack of methodological agreement between preclinical and clinical studies and the heterogeneity of stroke in humans compared to homogeneous strokes in animal models. Even when the international recommendations for preclinical stroke research, the Stroke Academic Industry Roundtable (STAIR criteria, were followed, we have still seen limited success in the clinic, examples being NXY-059 and haematopoietic growth factors which fulfilled nearly all the STAIR criteria. However, there are a number of neuroprotective treatments under investigation in clinical trials such as hypothermia and ebselen. Moreover, promising neuroprotective treatments based on a deeper understanding of the complex pathophysiology of ischemic stroke such as inhibitors of NADPH oxidases and PSD-95 are currently evaluated in preclinical studies. Further concepts to improve translation include the investigation of neuroprotectants in multicenter preclinical Phase III-type studies, improved animal models, and close alignment between clinical trial and preclinical methodologies. Future successful translation will require both new concepts for preclinical testing and innovative approaches based on mechanistic insights into the ischemic cascade.

  9. DNA evidence: current perspective and future challenges in India.

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    Verma, Sunil K; Goswami, Gajendra K

    2014-08-01

    Since the discovery of DNA fingerprinting technology in 1985 it has been used extensively as evidence in the court of law world-wide to establish the individual identity both in civil and criminal matters. In India, the first case of parentage dispute solved by the use of DNA fingerprinting technology was in 1989. Since then till date, the DNA technology has been used not only to resolve the cases of paternity and maternity disputes, but also for the establishment of individual identity in various criminal cases and for wildlife forensic identification. Since last half a decade, India is exercising to enact legislation on the use of DNA in the judicial realm and the draft 'Human DNA Bill-2012' is pending in the parliament. Largely, the promoters of forensic DNA testing have anticipated that DNA tests are nearly infallible and DNA technology could be the greatest single advance step in search for truth, conviction of the perpetrator, and acquittal of the innocent. The current article provides a comprehensive review on the status of DNA testing in India and elucidates the consequences of the admissibility of DNA as 'evidence' in the judicial dominion. In this backdrop of civil and criminal laws and changing ethical and societal attitudes, it is concluded that the DNA legislation in India and world-wide needs to be designed with utmost care. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Cardiorenal syndrome--current understanding and future perspectives.

    Science.gov (United States)

    Braam, Branko; Joles, Jaap A; Danishwar, Amir H; Gaillard, Carlo A

    2014-01-01

    Combined cardiac and renal dysfunction has gained considerable attention. Hypotheses about its pathogenesis have been formulated, albeit based on a relatively small body of experimental studies, and a clinical classification system has been proposed. Cardiorenal syndrome, as presently defined, comprises a heterogeneous group of acute and chronic clinical conditions, in which the failure of one organ (heart or kidney) initiates or aggravates failure of the other. This conceptual framework, however, has two major drawbacks: the first is that, despite worldwide interest, universally accepted definitions of cardiorenal syndrome are lacking and characterization of heart and kidney failure is not uniform. This lack of consistency hampers experimental studies on mechanisms of the disease. The second is that, although progress has been made in developing hypotheses for the pathogenesis of cardiorenal syndrome, these initiatives are at an impasse. No hierarchy has been identified in the myriad of haemodynamic and non-haemodynamic factors mediating cardiorenal syndrome. This Review discusses current understanding of cardiorenal syndrome and provides a roadmap for further studies in this field. Ultimately, discussion of the definition and characterization issues and of the lack of organization among pathogenetic factors is hoped to contribute to further advancement of this complex field.

  11. Cognitive Remediation in Schizophrenia: Current Status and Future Perspectives

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    Stefano Barlati

    2013-01-01

    Full Text Available Objectives. This study is aimed to review the current scientific literature on cognitive remediation in schizophrenia. In particular, the main structured protocols of cognitive remediation developed for schizophrenia are presented and the main results reported in recent meta-analyses are summarized. Possible benefits of cognitive remediation in the early course of schizophrenia and in subjects at risk for psychosis are also discussed. Methods. Electronic search of the relevant studies which appeared in the PubMed database until April 2013 has been performed and all the meta-analyses and review articles on cognitive remediation in schizophrenia have been also taken into account. Results. Numerous intervention programs have been designed, applied, and evaluated, with the objective of improving cognition and social functioning in schizophrenia. Several quantitative reviews have established that cognitive remediation is effective in reducing cognitive deficits and in improving functional outcome of the disorder. Furthermore, the studies available support the usefulness of cognitive remediation when applied in the early course of schizophrenia and even in subjects at risk of the disease. Conclusions. Cognitive remediation is a promising approach to improve real-world functioning in schizophrenia and should be considered a key strategy for early intervention in the psychoses.

  12. Personalized medicine in CLL: current status and future perspectives.

    Science.gov (United States)

    Rozovski, Uri; Hazan-Halevy, Inbal; Keating, Michael J; Estrov, Zeev

    2014-09-28

    Chronic lymphocytic leukemia (CLL) is the most common hematologic malignancy in the Western Hemisphere. Despite advances in research and the development of effective treatment regimens, CLL is still largely an incurable disease. Although several prognostic factors have been identified in recent years, most of the new prognostic factors are not utilized, and treatment decisions are still based on clinical staging and limited use of cytogenetic analysis. Patients with advanced disease are treated at diagnosis, whereas others, regardless of their prognostic indicators, are offered treatment only at disease progression. Furthermore, treatment guidelines for elderly or "unfit" patients are unavailable because most CLL trials have included mostly younger, healthier patients. Given theheterogeneity of the clinical manifestations and prognosis of CLL, patients are likely to benefit from a personalized therapeutic approach. Recent advances in CLL pathobiology research, the use of high-throughput technologies, and most importantly, the introduction of novel targeted therapies with high efficacy and low toxicity are currently transforming the treatment of CLL. A personalized approach that includes early intervention in selected patients with CLL is likely to bring physicians closer to the goal of attaining cures in most patients with CLL. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Fluconazole resistance in Candida species: a current perspective

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    Berkow EL

    2017-07-01

    Full Text Available Elizabeth L Berkow, Shawn R Lockhart Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA Abstract: Candida albicans and the emerging non-albicans Candida spp. have significant clinical relevance among many patient populations. Current treatment guidelines include fluconazole as a primary therapeutic option for the treatment of these infections, but it is only fungistatic against Candida spp. and both inherent and acquired resistance to fluconazole have been reported. Such mechanisms of resistance include increased drug efflux, alteration or increase in the drug target, and development of compensatory pathways for producing the target sterol, ergosterol. While many mechanisms of resistance observed in C. albicans are also found in the non-albicans species, there are also important and unexpected differences between species. Furthermore, mechanisms of fluconazole resistance in emerging Candida spp., including the global health threat Candida auris, are largely unknown. In order to preserve the utility of one of our fundamental antifungal drugs, fluconazole, it is essential that we fully appreciate the manner by which Candida spp. manifest resistance to it. Keywords: Candida, fluconazole resistance, ERG11, drug efflux, ergosterol

  14. Current state and perspectives of truffle genetics and sustainable biotechnology.

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    Poma, Anna; Limongi, Tania; Pacioni, Giovanni

    2006-09-01

    Mycorrhizal fungi belonging to the genus Tuber produce, after the establishment of a productive interaction with a plant host, hypogeous fruitbodies of great economic value known as ''truffles''. This review summarizes the state of art on life cycle, genetic, and biotechnological investigations of Tuber spp. The ascocarp formation in truffles is a consequence of the activation of the sexual phase of the biological cycle. The formation of a dikaryotic secondary mycelium and the karyogamy in the ascal cell (followed by meiosis with ascospores formation) have been hypothesized by several authors but some doubts yet arise from the Tuber cycle by considering that a series of abnormalities have been pointed out in respect to other Ascomycetes. It is unclear if binucleated hyphal cells are derived from the fusion of mononucleated cells belonging to mycelia from different mating types or from one only. According to the karyotypes of Tuber melanosporum, Tuber magnatum, and Tuber borchii, the numbers of hyphal chromosomes suggest a chromosome number of eight (2n); these values are in the range of those of several Ascomycetes and observed for Tuber aestivum (2n=10). The importance and growth in interest during the last years in the fungi protoplasts isolation and transformation techniques can be related to current developments in Tuber genetics and biotechnology. T. borchii could be transformed through liposome-mediated delivery of genetic material as mycelial protoplasts isolation and fusion with liposomes has already been established. On the other hand, Agrobacterium-mediated transformation has been successfully established for T. borchii.

  15. Current Perspectives on Desmoid Tumors: The Mayo Clinic Approach

    Energy Technology Data Exchange (ETDEWEB)

    Joglekar, Siddharth B. [Musculoskeletal Oncology, Mayo Clinic, Rochester, MN55905 (United States); Rose, Peter S.; Sim, Franklin, E-mail: sim.franklin@mayo.edu [Department of Orthopedics, Mayo Clinic, 200 1st ST SW, Rochester, MN 55905 (United States); Okuno, Scott [Department of Oncology, Mayo Clinic, Rochester, MN55905 (United States); Petersen, Ivy [Department of Radiation Oncology, Mayo Clinic, Rochester, MN55905 (United States)

    2011-08-08

    Desmoid tumors are a rare group of locally aggressive, non malignant tumors of fibroblastic origin that can lead to significant morbidity due to local invasion. Despite advances in the understanding of these tumors, their natural history is incompletely understood and the optimal treatment is still a matter of debate. Local control is the main goal of treatment and there has been a change in philosophy regarding the management of these tumors from aggressive surgical resection to function preservation. A multidisciplinary approach is essential to plan local control with acceptable morbidity. The current Mayo Clinic algorithm for the treatment of these tumors is based on institutional experience and the available evidence in the literature: asymptomatic/non progressive lesions away from vital structures are managed with observation and regular imaging; primary or recurrent desmoid tumors which are symptomatic or progressive or near vital structures are managed with wide surgical resection when wide surgical margins are possible with minimal functional and cosmetic loss. When positive or close surgical margins are likely, surgical resection with adjuvant radiotherapy or definitive radiotherapy is preferred. If likely functional or cosmetic deficit is unacceptable, radiotherapy is the treatment of choice. Unresectable lesions are considered for radiotherapy, chemotherapy or newer modalities however an unresectable lesion associated with a painful, functionless, infected extremity is managed with an amputation.

  16. Value of biomarkers in osteoarthritis: current status and perspectives

    Science.gov (United States)

    Lotz, M; Martel-Pelletier, J; Christiansen, C; Brandi, M-L; Bruyère, O; Chapurlat, R; Collette, J; Cooper, C; Giacovelli, G; Kanis, J A; Karsdal, M A; Kraus, V; Lems, W F; Meulenbelt, I; Pelletier, J-P; Raynauld, J-P; Reiter-Niesert, S; Rizzoli, R; Sandell, L J; Van Spil, W E; Reginster, J-Y

    2013-01-01

    Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the ‘omics’ (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and

  17. EPMA position paper in cancer: current overview and future perspectives.

    Science.gov (United States)

    Grech, Godfrey; Zhan, Xianquan; Yoo, Byong Chul; Bubnov, Rostyslav; Hagan, Suzanne; Danesi, Romano; Vittadini, Giorgio; Desiderio, Dominic M

    2015-01-01

    At present, a radical shift in cancer treatment is occurring in terms of predictive, preventive, and personalized medicine (PPPM). Individual patients will participate in more aspects of their healthcare. During the development of PPPM, many rapid, specific, and sensitive new methods for earlier detection of cancer will result in more efficient management of the patient and hence a better quality of life. Coordination of the various activities among different healthcare professionals in primary, secondary, and tertiary care requires well-defined competencies, implementation of training and educational programs, sharing of data, and harmonized guidelines. In this position paper, the current knowledge to understand cancer predisposition and risk factors, the cellular biology of cancer, predictive markers and treatment outcome, the improvement in technologies in screening and diagnosis, and provision of better drug development solutions are discussed in the context of a better implementation of personalized medicine. Recognition of the major risk factors for cancer initiation is the key for preventive strategies (EPMA J. 4(1):6, 2013). Of interest, cancer predisposing syndromes in particular the monogenic subtypes that lead to cancer progression are well defined and one should focus on implementation strategies to identify individuals at risk to allow preventive measures and early screening/diagnosis. Implementation of such measures is disturbed by improper use of the data, with breach of data protection as one of the risks to be heavily controlled. Population screening requires in depth cost-benefit analysis to justify healthcare costs, and the parameters screened should provide information that allow an actionable and deliverable solution, for better healthcare provision.

  18. Smartphone applications to support weight loss: current perspectives.

    Science.gov (United States)

    Pellegrini, Christine A; Pfammatter, Angela F; Conroy, David E; Spring, Bonnie

    2015-07-01

    Lower cost alternatives are needed for the traditional in-person behavioral weight loss programs to overcome challenges of lowering the worldwide prevalence of overweight and obesity. Smartphones have become ubiquitous and provide a unique platform to aid in the delivery of a behavioral weight loss program. The technological capabilities of a smartphone may address certain limitations of a traditional weight loss program, while also reducing the cost and burden on participants, interventionists, and health care providers. Awareness of the advantages smartphones offer for weight loss has led to the rapid development and proliferation of weight loss applications (apps). The built-in features and the mechanisms by which they work vary across apps. Although there are an extraordinary number of a weight loss apps available, most lack the same magnitude of evidence-based behavior change strategies typically used in traditional programs. As features develop and new capabilities are identified, we propose a conceptual model as a framework to guide the inclusion of features that can facilitate behavior change and lead to reductions in weight. Whereas the conventional wisdom about behavior change asserts that more is better (with respect to the number of behavior change techniques involved), this model suggests that less may be more because extra techniques may add burden and adversely impact engagement. Current evidence is promising and continues to emerge on the potential of smartphone use within weight loss programs; yet research is unable to keep up with the rapidly improving smartphone technology. Future studies are needed to refine the conceptual model's utility in the use of technology for weight loss, determine the effectiveness of intervention components utilizing smartphone technology, and identify novel and faster ways to evaluate the ever-changing technology.

  19. Risk management of seasonal influenza during pregnancy: current perspectives

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    Yudin MH

    2014-07-01

    Full Text Available Mark H Yudin The Department of Obstetrics and Gynecology, St Michael's Hospital, Li Ka Shing Knowledge Institute, University of Toronto, Toronto, ON, Canada Abstract: Influenza poses unique risks to pregnant women, who are particularly susceptible to morbidity and mortality. Historically, pregnant women have been overrepresented among patients with severe illness and complications from influenza, and have been more likely to require hospitalization and intensive care unit admission. An increased risk of adverse outcomes is also present for fetuses/neonates born to women affected by influenza during pregnancy. These risks to mothers and babies have been observed during both nonpandemic and pandemic influenza seasons. During the H1N1 influenza pandemic of 2009–2010, pregnant women were more likely to be hospitalized or admitted to intensive care units, and were at higher risk of death compared to nonpregnant adults. Vaccination remains the most effective intervention to prevent severe illness, and antiviral medications are an important adjunct to ameliorate disease when it occurs. Unfortunately, despite national guidelines recommending universal vaccination for women who are pregnant during influenza season, actual vaccination rates do not achieve desired targets among pregnant women. Pregnant women are also sometimes reluctant to use antiviral medications during pregnancy. Some of the barriers to use of vaccines and medications during pregnancy are a lack of knowledge of recommendations and of safety data. By improving knowledge and understanding of influenza and vaccination recommendations, vaccine acceptance rates among pregnant women can be improved. Currently, the appropriate use of vaccination and antiviral medications is the best line of defense against influenza and its sequelae among pregnant women, and strategies to increase acceptance are crucial. This article will review the importance of influenza in pregnancy, and discuss

  20. Complications and challenges associated with polycystic ovary syndrome: current perspectives

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    Palomba S

    2015-07-01

    Full Text Available Stefano Palomba,1 Susanna Santagni,1 Angela Falbo,1 Giovanni Battista La Sala1,21Unit of Obstetrics and Gynecology, Arcispedale Santa Maria Nuova-Scientific Institute of Treatment and Care (IRCCS, Reggio Emilia, 2Department of Obstetrics and Gynecology, University of Modena and Reggio Emilia, Modena, ItalyAbstract: Polycystic ovary syndrome (PCOS represents the most common endocrine dysfunction in fertile women and it is considered a heterogeneous and multifaceted disorder, with multiple reproductive and metabolic phenotypes which differently affect the early- and long-term syndrome’s risks. Women with PCOS present an adverse reproductive profile, including a high risk of pregnancy-induced hypertension, preeclampsia, and gestational diabetes mellitus. Patients with PCOS present not only a higher prevalence of classic cardiovascular risk factors, such as hypertension, dyslipidemia, and type-2 diabetes mellitus, but also of nonclassic cardiovascular risk factors, including mood disorders, such as depression and anxiety. Moreover, at the moment, clinical data on cardiovascular morbidity and mortality in women with PCOS are controversial. Finally, women with PCOS show an increased risk of endometrial cancer compared to non-PCOS healthy women, particularly during premenopausal period. Currently, we are unable to clarify if the increased PCOS early- and long-term risks are totally due to PCOS per se or mostly due to obesity, in particular visceral obesity, that characterized the majority of PCOS patients. In any case, the main endocrine and gynecological scientific societies agree to consider women with PCOS at increased risk of obstetric, cardiometabolic, oncology, and psychological complications throughout life, and it is recommended that these women be accurately assessed with periodic follow-up.Keywords: cardiovascular disease, infertility, polycystic ovary syndrome, PCOS, pregnancy

  1. Global properties of magnetotail current sheet flapping: THEMIS perspectives

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    A. Runov

    2009-01-01

    Full Text Available A sequence of magnetic field oscillations with an amplitude of up to 30 nT and a time scale of 30 min was detected by four of the five THEMIS spacecraft in the magnetotail plasma sheet. The probes P1 and P2 were at X=−15.2 and −12.7 RE and P3 and P4 were at X=−7.9 RE. All four probes were at −6.5>Y>−7.5 RE (major conjunction. Multi-point timing analysis of the magnetic field variations shows that fronts of the oscillations propagated flankward (dawnward and Earthward nearly perpendicular to the direction of the magnetic maximum variation (B1 at velocities of 20–30 km/s. These are typical characteristics of current sheet flapping motion. The observed anti-correlation between ∂B1/∂t and the Z-component of the bulk velocity make it possible to estimate a flapping amplitude of 1 to 3 RE. The cross-tail scale wave-length was found to be about 5 RE. Thus the flapping waves are steep tail-aligned structures with a lengthwise scale of >10 RE. The intermittent plasma motion with the cross-tail velocity component changing its sign, observed during flapping, indicates that the flapping waves were propagating through the ambient plasma. Simultaneous observations of the magnetic field variations by THEMIS ground-based magnetometers show that the flapping oscillations were observed during the growth phase of a substorm.

  2. Aerial wildfire fighting: history, current situation, problems and perspectives

    Directory of Open Access Journals (Sweden)

    A. V. Bryukhanov

    2017-10-01

    Full Text Available Nowadays aviation is among the most effective ways of early detection and suppression of wildfires. At the moment for the aerial wildfire fighting a few dozen models of aircraft are used worldwide, which are regularly modernized and renewed. In this article, authors give information about the history of fighting wildfires from the air, as well as analyze the current state of the issue with the use of aircraft and helicopter airtankers for firefighting, both at international level and in the territory of the Russian Federation. It is revealed that the most popular in the world still are the ground-based firefighting aircraft (regardless of the class of the carrying capacity. Amphibious firefighting aircraft now exist only in light (carrying capacity up to 5 tons and in medium type (capacity up to 15 tons. Among the helicopter aviation, heavy firefighting helicopters are mostly widely spread, as well as medium multipurpose helicopters, which are, apart from suppression, involved into delivery of people and goods to forest fire sites. The article is devoted to the main directions, according to which the development of aircraft tanker equipment abroad and in Russia occurs. The attention is directed to the most promising developments, and specific recommendations on how to increase the effectiveness of the fire aviation usage in Russia are given. Based on the studies carried out, a conclusion is drawn that for different countries there can be promising different types of firefighting aircraft, considering their landing field infrastructure, characteristics of forests and hydro systems, as well as the total area of the forest fund.

  3. Prognostic stratification of colorectal cancer patients: current perspectives

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    Schneider NI

    2014-07-01

    Full Text Available Nora I Schneider, Cord LangnerInstitute of Pathology, Medical University of Graz, Graz, AustriaAbstract: Tumor staging according to the American Joint Committee on Cancer/Union for International Cancer Control tumor, node, metastasis (TNM system is currently regarded as the standard for staging of patients with colorectal cancer. This system provides the strongest prognostic information for patients with early stage disease and those with advanced disease. For patients with intermediate levels of disease, it is less able to predict disease outcome. Therefore, additional prognostic markers are needed to improve the management of affected patients. Ideal markers are readily assessable on hematoxylin and eosin-stained tumor slides, and in this way are easily applicable worldwide. This review summarizes the histological features of colorectal cancer that can be used for prognostic stratification. Specifically, we refer to the different histological variants of colorectal cancer that have been identified, each of these variants carrying distinct prognostic significance. Established markers of adverse outcomes are lymphatic and venous invasion, as well as perineural invasion, but underreporting still occurs in the routine setting. Tumor budding and tumor necrosis are recent advances that may help to identify patients at high risk for recurrence. The prognostic significance of the antitumor inflammatory response has been known for quite a long time, but a lack of standardization prevented its application in routine pathology. However, scales to assess intra- and peritumoral inflammation have recently emerged, and can be expected to strengthen the prognostic significance of the pathology report.Keywords: colorectal cancer, lymphatic invasion, blood-vessel invasion, perineural invasion, tumor budding, tumor necrosis

  4. Current perspectives on genetically modified crops and detection methods.

    Science.gov (United States)

    Kamle, Madhu; Kumar, Pradeep; Patra, Jayanta Kumar; Bajpai, Vivek K

    2017-07-01

    Genetically modified (GM) crops are the fastest adopted commodities in the agribiotech industry. This market penetration should provide a sustainable basis for ensuring food supply for growing global populations. The successful completion of two decades of commercial GM crop production (1996-2015) is underscored by the increasing rate of adoption of genetic engineering technology by farmers worldwide. With the advent of introduction of multiple traits stacked together in GM crops for combined herbicide tolerance, insect resistance, drought tolerance or disease resistance, the requirement of reliable and sensitive detection methods for tracing and labeling genetically modified organisms in the food/feed chain has become increasingly important. In addition, several countries have established threshold levels for GM content which trigger legally binding labeling schemes. The labeling of GM crops is mandatory in many countries (such as China, EU, Russia, Australia, New Zealand, Brazil, Israel, Saudi Arabia, Korea, Chile, Philippines, Indonesia, Thailand), whereas in Canada, Hong Kong, USA, South Africa, and Argentina voluntary labeling schemes operate. The rapid adoption of GM crops has increased controversies, and mitigating these issues pertaining to the implementation of effective regulatory measures for the detection of GM crops is essential. DNA-based detection methods have been successfully employed, while the whole genome sequencing using next-generation sequencing (NGS) technologies provides an advanced means for detecting genetically modified organisms and foods/feeds in GM crops. This review article describes the current status of GM crop commercialization and discusses the benefits and shortcomings of common and advanced detection systems for GMs in foods and animal feeds.

  5. Diagnosis and management of microscopic colitis: current perspectives

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    Bohr J

    2014-08-01

    Full Text Available Johan Bohr,1,3 Anna Wickbom,1,3 Agnes Hegedus,2 Nils Nyhlin,1,3 Elisabeth Hultgren Hörnquist,3 Curt Tysk1,3 1Division of Gastroenterology, Department of Medicine, 2Department of Laboratory Medicine/Pathology, Örebro University Hospital, Örebro, 3School of Health and Medical Sciences, Örebro University, Örebro, Sweden Abstract: Collagenous colitis and lymphocytic colitis, together constituting microscopic colitis, are common causes of chronic diarrhea. They are characterized clinically by chronic nonbloody diarrhea and a macroscopically normal colonic mucosa where characteristic histopathological findings are seen. Previously considered rare, they now have emerged as common disorders that need to be considered in the investigation of the patient with chronic diarrhea. The annual incidence of each disorder is five to ten per 100,000 inhabitants, with a peak incidence in 60- to 70-year-old individuals and a predominance of female patients in collagenous colitis. The etiology and pathophysiology are not well understood, and the current view suggests an uncontrolled mucosal immune reaction to various luminal agents in predisposed individuals. Clinical symptoms comprise chronic diarrhea, abdominal pain, fatigue, weight loss, and fecal incontinence that may impair the patient's health-related quality of life. An association is reported with other autoimmune disorders, such as celiac disease, thyroid disorders, diabetes mellitus, and arthritis. The best-documented treatment, both short-term and long-term, is budesonide, which induces clinical remission in up to 80% of patients after 8 weeks' treatment. However, after successful budesonide therapy is ended, recurrence of clinical symptoms is common, and the best possible long-term management deserves further study. The long-term prognosis is good, and the risk of complications, including colonic cancer, is low. We present an update of the epidemiology, pathogenesis, diagnosis, and management of

  6. Artificial urinary sphincters for male stress urinary incontinence: current perspectives.

    Science.gov (United States)

    Cordon, Billy H; Singla, Nirmish; Singla, Ajay K

    2016-01-01

    The artificial urinary sphincter (AUS), which has evolved over many years, has become a safe and reliable treatment for stress urinary incontinence and is currently the gold standard. After 4 decades of existence, there is substantial experience with the AUS. Today AUS is most commonly placed for postprostatectomy stress urinary incontinence. Only a small proportion of urologists routinely place AUS. In a survey in 2005, only 4% of urologists were considered high-volume AUS implanters, performing >20 per year. Globally, ~11,500 AUSs are placed annually. Over 400 articles have been published regarding the outcomes of AUS, with a wide variance in success rates ranging from 61% to 100%. Generally speaking, the AUS has good long-term outcomes, with social continence rates of ~79% and high patient satisfaction usually between 80% and 90%. Despite good outcomes, a substantial proportion of patients, generally ~25%, will require revision surgery, with the rate of revision increasing with time. Complications requiring revision include infection, urethral atrophy, erosion, and mechanical failure. Most infections are gram-positive skin flora. Urethral atrophy and erosion lie on a spectrum resulting from the same problem, constant urethral compression. However, these two complications are managed differently. Mechanical failure is usually a late complication occurring on average later than infection, atrophy, or erosions. Various techniques may be used during revisions, including cuff relocation, downsizing, transcorporal cuff placement, or tandem cuff placement. Patient satisfaction does not appear to be affected by the need for revision as long as continence is restored. Additionally, AUS following prior sling surgery has comparable outcomes to primary AUS placement. Several new inventions are on the horizon, although none have been approved for use in the US at this point.

  7. Comparative proteomics evaluation of plasma exosome isolation techniques and assessment of the stability of exosomes in normal human blood plasma.

    Science.gov (United States)

    Kalra, Hina; Adda, Christopher G; Liem, Michael; Ang, Ching-Seng; Mechler, Adam; Simpson, Richard J; Hulett, Mark D; Mathivanan, Suresh

    2013-11-01

    Exosomes are nanovesicles released by a variety of cells and are detected in body fluids including blood. Recent studies have highlighted the critical application of exosomes as personalized targeted drug delivery vehicles and as reservoirs of disease biomarkers. While these research applications have created significant interest and can be translated into practice, the stability of exosomes needs to be assessed and exosome isolation protocols from blood plasma need to be optimized. To optimize methods to isolate exosomes from blood plasma, we performed a comparative evaluation of three exosome isolation techniques (differential centrifugation coupled with ultracentrifugation, epithelial cell adhesion molecule immunoaffinity pull-down, and OptiPrep(TM) density gradient separation) using normal human plasma. Based on MS, Western blotting and microscopy results, we found that the OptiPrep(TM) density gradient method was superior in isolating pure exosomal populations, devoid of highly abundant plasma proteins. In addition, we assessed the stability of exosomes in plasma over 90 days under various storage conditions. Western blotting analysis using the exosomal marker, TSG101, revealed that exosomes are stable for 90 days. Interestingly, in the context of cellular uptake, the isolated exosomes were able to fuse with target cells revealing that they were indeed biologically active. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. The hygiene hypothesis: current perspectives and future therapies

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    Stiemsma LT

    2015-07-01

    Full Text Available Leah T Stiemsma,1,2 Lisa A Reynolds,3 Stuart E Turvey,1,2,4 B Brett Finlay1,3,5 1Department of Microbiology & Immunology, University of British Columbia, 2The Child and Family Research Institute, 3Michael Smith Laboratories, University of British Columbia, 4Department of Pediatrics, University of British Columbia, 5Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada Abstract: Developed countries have experienced a steady increase in atopic disease and disorders of immune dysregulation since the 1980s. This increase parallels a decrease in infectious diseases within the same time period, while developing countries seem to exhibit the opposite effect, with less immune dysregulation and a higher prevalence of infectious disease. The “hygiene hypothesis”, proposed by Strachan in 1989, aimed to explain this peculiar generational rise in immune dysregulation. However, research over the past 10 years provides evidence connecting the commensal and symbiotic microbes (intestinal microbiota and parasitic helminths with immune development, expanding the hygiene hypothesis into the “microflora” and “old friends” hypotheses, respectively. There is evidence that parasitic helminths and commensal microbial organisms co-evolved with the human immune system and that these organisms are vital in promoting normal immune development. Current research supports the potential for manipulation of the bacterial intestinal microbiota to treat and even prevent immune dysregulation in the form of atopic disease and other immune-mediated disorders (namely inflammatory bowel disease and type 1 diabetes. Both human and animal model research are crucial in understanding the mechanistic links between these intestinal microbes and helminth parasites, and the human immune system. Pro-, pre-, and synbiotic, as well as treatment with live helminth and excretory/secretory helminth product therapies, are all potential

  9. RCOF in European region: current status and future perspective

    Science.gov (United States)

    Hovsepyan, A.

    2010-09-01

    Regional Climate Outlook Forums are a key component of WMO WCASP/CLIPS activities. The RCOF process pioneered in Africa in late 1990s, since then it spread worldwide, and at present climate outlook forums are being conducted nearly in all regions all over the world. The RCOF brings together experts from a climatologically homogeneous region and provides consensus based climate prediction and information, which has critical socio-economic significance. This information has been applied to reducing climate-related risks and supporting sustainable development. The RCOF process has facilitated a better understanding of the links between the past, current and future evolution of the climate system and its consequences for Members' socio-economic activities. RCOFs have greatly enhanced interactions and exchange of information between providers and users of climate information. In addition, RCOFs contribute substantially to training and capacity building in the regions targeted at. In RA VI the RCOF process was launched in 2008. The South-East European Climate Outlook Forum (SEECOF) mechanism covers mainly countries of South East Europe and Caucasus. Two SEECOFs have been successfully conducted in 2008 and 2009: SEECOF-I took place in Zagreb/Croatia in June 2008 and SEECOF-II was hosted by Hungary, Budapest, in November 2009. SEECOF-III was held as an online COF. Nevertheless, the RCOF mechanism in RA VI still needs substantial support in order to strengthen the process, to better involve the participating countries and users, to sharpen the communication of the consensus forecasts to build trust amongst the user communities, and most importantly to achieve sustainability, which is one of the priority tasks of the RAVI Working Group on Climate and Hydrology (WG CH). Through the Task Team on Regional Climate Outlook Forums (TT RCOF) the WG CH has taken responsibility for the co-ordination of the RCOF process in RA VI, in order to extend it to other parts of RA VI region

  10. Red blood cell transfusion in preterm neonates: current perspectives

    Directory of Open Access Journals (Sweden)

    Chirico G

    2014-06-01

    were evaluated, the girls in the liberal group had the most significant abnormalities. In conclusion, it would seem preferable to adopt restrictive criteria. Current recommendation on transfusion therapy should be revised to take into account this suggestion.Keywords: preterm neonates, red blood cells, transfusion, anemia

  11. Artificial urinary sphincters for male stress urinary incontinence: current perspectives

    Directory of Open Access Journals (Sweden)

    Cordon BH

    2016-07-01

    Full Text Available Billy H Cordon,1 Nirmish Singla,1 Ajay K Singla2 1Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, 2Department of Urology, University of Toledo College of Medicine, Toledo, OH, USA Abstract: The artificial urinary sphincter (AUS, which has evolved over many years, has become a safe and reliable treatment for stress urinary incontinence and is currently the gold standard. After 4 decades of existence, there is substantial experience with the AUS. Today AUS is most commonly placed for postprostatectomy stress urinary incontinence. Only a small proportion of urologists routinely place AUS. In a survey in 2005, only 4% of urologists were considered high-volume AUS implanters, performing >20 per year. Globally, ~11,500 AUSs are placed annually. Over 400 articles have been published regarding the outcomes of AUS, with a wide variance in success rates ranging from 61% to 100%. Generally speaking, the AUS has good long-term outcomes, with social continence rates of ~79% and high patient satisfaction usually between 80% and 90%. Despite good outcomes, a substantial proportion of patients, generally ~25%, will require revision surgery, with the rate of revision increasing with time. Complications requiring revision include infection, urethral atrophy, erosion, and mechanical failure. Most infections are gram-positive skin flora. Urethral atrophy and erosion lie on a spectrum resulting from the same problem, constant urethral compression. However, these two complications are managed differently. Mechanical failure is usually a late complication occurring on average later than infection, atrophy, or erosions. Various techniques may be used during revisions, including cuff relocation, downsizing, transcorporal cuff placement, or tandem cuff placement. Patient satisfaction does not appear to be affected by the need for revision as long as continence is restored. Additionally, AUS following prior sling surgery has comparable

  12. Cardiovascular comorbidity in patients with restless legs syndrome: current perspectives

    Directory of Open Access Journals (Sweden)

    Vargas-Pérez NJ

    2017-05-01

    bulk of the evidence favors such an association. Conclusion: The current evidence in general supports the association between RLS/PLMS and CVD. The variability of results likely represent differences in study designs, RLS criteria used, RLS severity, duration of disease, and time of follow-up between the studies. As the association between RLS/PLMS and CVD is not definitive at this time, further suggested studies are outlined. Keywords: restless legs syndrome, periodic limb movements in sleep, cardiovascular disease, heart disease, hypertension, stroke, chronic kidney disease

  13. Geology and religion - historical perspective and current problems

    Science.gov (United States)

    Kölbl-Ebert, Martina

    2010-05-01

    Today, when referring to the relationship between geology and religion, people usually at once think of Christian (and other) fundamentalists and their chronic palaeontological illiteracy leading to Creationism, to Intelligent Design, and a distrust of science in general among them most prominently geology, palaeontology and evolutionary biology. Thus the relationship of geology and religion is usually considered to be under strain. In former times things used to be quite different, and for most of human history the observation of geological phenomena and the acquisition of geological expertise was intimately connected with religious ideas. The Judeo-Christian sense of a finite Earth history prepared the ground for accepting the Earth's different strata as testimony to the development of our globe through time. It was this religious, theological framework, from which the early geology started to evolve. However, with increasing observations there was a growing mismatch between what was expected according to ancient, scriptural authorities and the actual data. The release of geology from religious connotations or associations was a development closely connected with the Enlightenment, when geology and religion started to drift apart not with a violent rupture but in a subtle and sometimes circuitous manner. However, outside the group of people with geological expertise, not all was smooth and peaceful, and some conservative clergymen as well as laypersons were rather shocked by the new ideas that came with geology: the immensity of the timescale, a dynamic Earth, not just a ruin shaped by the Deluge, and a dynamic biology too with the Darwinian theory of evolution, which was founded in part on palaeontological evidence and the assumption of a long geological time scale. Nevertheless and interestingly the Creationism we face today is a rather recent phenomenon influenced by a number of motives, most of them philosophical and theological in nature. And so, the current

  14. Development of a rapid lateral flow immunoassay test for detection of exosomes previously enriched from cell culture medium and body fluids

    Directory of Open Access Journals (Sweden)

    Myriam Oliveira-Rodríguez

    2016-08-01

    Full Text Available Exosomes are cell-secreted nanovesicles (40–200 nm that represent a rich source of novel biomarkers in the diagnosis and prognosis of certain diseases. Despite the increasingly recognized relevance of these vesicles as biomarkers, their detection has been limited due in part to current technical challenges in the rapid isolation and analysis of exosomes. The complexity of the development of analytical platforms relies on the heterogeneous composition of the exosome membrane. One of the most attractive tests is the inmunochromatographic strips, which allow rapid detection by unskilled operators. We have successfully developed a novel lateral flow immunoassay (LFIA for the detection of exosomes based on the use of tetraspanins as targets. We have applied this platform for the detection of exosomes purified from different sources: cell culture supernatants, human plasma and urine. As proof of concept, we explored the analytical potential of this LFIA platform to accurately quantify exosomes purified from a human metastatic melanoma cell line. The one-step assay can be completed in 15 min, with a limit of detection of 8.54×105 exosomes/µL when a blend of anti-CD9 and anti-CD81 were selected as capture antibodies and anti-CD63 labelled with gold nanoparticles as detection antibody. Based on our results, this platform could be well suited to be used as a rapid exosome quantification tool, with promising diagnostic applications, bearing in mind that the detection of exosomes from different sources may require adaptation of the analytical settings to their specific composition.

  15. Development of a rapid lateral flow immunoassay test for detection of exosomes previously enriched from cell culture medium and body fluids.

    Science.gov (United States)

    Oliveira-Rodríguez, Myriam; López-Cobo, Sheila; Reyburn, Hugh T; Costa-García, Agustín; López-Martín, Soraya; Yáñez-Mó, María; Cernuda-Morollón, Eva; Paschen, Annette; Valés-Gómez, Mar; Blanco-López, Maria Carmen

    2016-01-01

    Exosomes are cell-secreted nanovesicles (40-200 nm) that represent a rich source of novel biomarkers in the diagnosis and prognosis of certain diseases. Despite the increasingly recognized relevance of these vesicles as biomarkers, their detection has been limited due in part to current technical challenges in the rapid isolation and analysis of exosomes. The complexity of the development of analytical platforms relies on the heterogeneous composition of the exosome membrane. One of the most attractive tests is the inmunochromatographic strips, which allow rapid detection by unskilled operators. We have successfully developed a novel lateral flow immunoassay (LFIA) for the detection of exosomes based on the use of tetraspanins as targets. We have applied this platform for the detection of exosomes purified from different sources: cell culture supernatants, human plasma and urine. As proof of concept, we explored the analytical potential of this LFIA platform to accurately quantify exosomes purified from a human metastatic melanoma cell line. The one-step assay can be completed in 15 min, with a limit of detection of 8.54×10(5) exosomes/µL when a blend of anti-CD9 and anti-CD81 were selected as capture antibodies and anti-CD63 labelled with gold nanoparticles as detection antibody. Based on our results, this platform could be well suited to be used as a rapid exosome quantification tool, with promising diagnostic applications, bearing in mind that the detection of exosomes from different sources may require adaptation of the analytical settings to their specific composition.

  16. Current Challenges for K-12 Dance Education and Development: Perspectives from Higher Education

    Science.gov (United States)

    Risner, Doug

    2007-01-01

    From an administrative perspective, this article investigates equity issues in dance education, and current challenges and opportunities for leadership in postsecondary dance programs involved in teacher education and certification. Although dance education is varied in content and environment, much is shared in terms of common goals for gender…

  17. Surveys of current status in biomedical science grant review: funding organisations' and grant reviewers' perspectives

    DEFF Research Database (Denmark)

    Schroter, Sara; Groves, Trish; Højgaard, Liselotte

    2010-01-01

    The objectives of this research were (a) to describe the current status of grant review for biomedical projects and programmes from the perspectives of international funding organisations and grant reviewers, and (b) to explore funders' interest in developing uniform requirements for grant review...

  18. The emerging roles of exosomes in tumor-stroma interaction.

    Science.gov (United States)

    Fu, Hailong; Yang, Huan; Zhang, Xu; Xu, Wenrong

    2016-09-01

    The tumor-stroma interaction is critical for the development and progression of cancer. Cancer-associated fibroblasts (CAFs), one of the major components of the tumor stroma, can promote tumor growth and metastasis. Exosomes are secreted microvesicles that mediate cell-to-cell communication. Exosomal contents, including proteins, nucleic acids, and lipids, can be shuttled from donor cells to target cells. Recent studies suggest that exosomes play important roles in the tumor-stroma interaction. Herein, we review the multifaceted roles of exosomes in the tumor-stroma interaction and the underlying molecular mechanisms. Literature search for all relevant publications was performed on PubMed databases. The keywords of exosomes, tumor, stroma, CAFs, mesenchymal stem cells (MSCs) and other closely related terms were used for searching. Tumor cell-derived exosomes induce the differentiation of fibroblasts and MSCs into CAFs. In turn, exosomes secreted by CAFs promote tumor growth, metastasis, and drug resistance through distinct mechanisms. Moreover, exosomes from stromal cells can be used as therapeutic vehicles for the delivery of anticancer drugs. Tumor cells communicate with CAFs through exosomes, which establishes a bidirectional cross talk to promote tumor growth, metastasis, and drug resistance. Targeting exosomes in tumor-stroma interaction may have important implications for anticancer therapy.

  19. Exosomal Secretion of Cytoplasmic Prostate Cancer Xenograft-derived Proteins *S⃞

    Science.gov (United States)

    Jansen, Flip H.; Krijgsveld, Jeroen; van Rijswijk, Angelique; van den Bemd, Gert-Jan; van den Berg, Mirella S.; van Weerden, Wytske M.; Willemsen, Rob; Dekker, Lennard J.; Luider, Theo M.; Jenster, Guido

    2009-01-01

    Novel markers for prostate cancer (PCa) are needed because current established markers such as prostate-specific antigen lack diagnostic specificity and prognostic value. Proteomics analysis of serum from mice grafted with human PCa xenografts resulted in the identification of 44 tumor-derived proteins. Besides secreted proteins we identified several cytoplasmic proteins, among which were most subunits of the proteasome. Native gel electrophoresis and sandwich ELISA showed that these subunits are present as proteasome complexes in the serum from xenograft-bearing mice. We hypothesized that the presence of proteasome subunits and other cytoplasmic proteins in serum of xenografted mice could be explained by the secretion of small vesicles by cancer cells, so-called exosomes. Therefore, mass spectrometry and Western blotting analyses of the protein content of exosomes isolated from PCa cell lines was performed. This resulted in the identification of mainly cytoplasmic proteins of which several had previously been identified in the serum of xenografted mice, including proteasome subunits. The isolated exosomes also contained RNA, including the gene fusion TMPRSS2-ERG product. These observations suggest that although their function is not clearly defined cancer-derived exosomes offer possibilities for the identification of novel biomarkers for PCa. PMID:19204029

  20. GMSC-Derived Exosomes Combined with a Chitosan/Silk Hydrogel Sponge Accelerates Wound Healing in a Diabetic Rat Skin Defect Model

    Directory of Open Access Journals (Sweden)

    Quan Shi

    2017-11-01

    Full Text Available Background: Delayed wound healing in diabetic patients is one of the most challenging complications in clinical medicine, as it poses a greater risk of gangrene, amputation and even death. Therefore, a novel method to promote diabetic wound healing is of considerable interest at present. Previous studies showed that injection of MSC-derived exosomes has beneficial effects on wound healing. In current studies, we aimed to isolate exosomes derived from gingival mesenchymal stem cells (GMSCs and then loading them to the chitosan/silk hydrogel sponge to evaluate the effects of this novel non-invasive method on skin defects in diabetic rats.Methods: GMSCs were isolated from human gingival connective tissue and characterized by surface antigen analysis and in vitro multipotent differentiation. The cell supernatant was collected to isolate the exosomes. The exosomes were characterized by transmission electron microscopy, Western blot and size distribution analysis. The chitosan/silk-based hydrogel sponge was prepared using the freeze-drying method and then structural and physical properties were characterized. Then, the exosomes were added to the hydrogel and tested in a diabetic rat skin defect model. The effects were evaluated by wound area measurement, histological, immunohistochemical and immunofluorescence analysis.Results: We have successfully isolated GMSCs and exosomes with a mean diameter of 127 nm. The chitosan/silk hydrogel had the appropriate properties of swelling and moisture retention capacity. The in vivo studies showed that the incorporating of GMSC-derived exosomes to hydrogel could effectively promote healing of diabetic skin defects. The histological analysis revealed more neo-epithelium and collagen in the hydrogel-exosome group. In addition, the hydrogel-exosome group had the highest microvessel density and nerve density.Conclusions: The combination of GMSC-derived exosomes and hydrogel could effectively promote skin wound healing

  1. Current perspectives on the role of TRAMP in nuclear RNA surveillance and quality control

    OpenAIRE

    Pan K; Huang Z; Lee JTH; Wong CM

    2015-01-01

    Kewu Pan, Zhe Huang, Jimmy Tsz Hang Lee, Chi-Ming Wong State Key Laboratory of Pharmaceutical Biotechnology, Department of Medicine, Shenzhen Institute of Research and Innovation, the University of Hong Kong, Pokfulam, Hong Kong Abstract: The TRAMP complex assists the nuclear exosome to degrade a broad range of ribonucleic acid (RNA) substrates by increasing both exoribonucleolytic activity and substrate specificity. However, how the interactions between the TRAMP subunits and the components...

  2. Urinary Exosomes and Their Cargo: Potential Biomarkers for Mineralocorticoid Arterial Hypertension?

    Directory of Open Access Journals (Sweden)

    Eric R. Barros

    2017-09-01

    Full Text Available Arterial hypertension (AHT currently affects approximately 40% of adults worldwide, and its pathological mechanisms are mainly related to renal, vascular, and endocrine systems. Steroid hormones as aldosterone and cortisol are highly relevant to human endocrine physiology, and also to endocrine hypertension. Pathophysiological conditions, such as primary aldosteronism, affect approximately 10% of patients diagnosed with AHT and are secondary to a high production of aldosterone, increasing the risk also for cardiovascular damage and heart diseases. Excess of aldosterone or cortisol increases the activity of the mineralocorticoid receptor (MR in epithelial and non-epithelial cells. Current research in this field highlights the potential regulatory mechanisms of the MR pathway, including pre-receptor regulation of the MR (action of 11BHSD2, MR activating proteins, and the downstream genes/proteins sensitive to MR (e.g., epithelial sodium channel, NCC, NKCC2. Mineralocorticoid AHT is present in 15–20% of hypertensive subjects, but the mechanisms associated to this condition have been poorly described, due mainly to the absence of reliable biomarkers. In this way, steroids, peptides, and lately urinary exosomes are thought to be potential reporters of biological processes. This review highlight exosomes and their cargo as potential biomarkers of metabolic changes associated to mineralocorticoid AHT. Recent reports have shown the presence of RNA, microRNAs, and proteins in urinary exosomes, which could be used as biomarkers in physiological and pathophysiological conditions. However, more studies are needed in order to benefit from exosomes and the exosomal cargo as a diagnostic tool in mineralocorticoid AHT.

  3. Isolation of nanoscale exosomes using viscoelastic effect

    Science.gov (United States)

    Hu, Guoqing; Liu, Chao

    2017-11-01

    Exosomes, molecular cargos secreted by almost all mammalian cells, are considered as promising biomarkers to identify many diseases including cancers. However, the small size of exosomes (30-200 nm) poses serious challenges on their isolation from the complex media containing a variety of extracellular vesicles (EVs) of different sizes, especially in small sample volumes. Here we develop a viscoelasticity-based microfluidic system to directly separate exosomes from cell culture media or serum in a continuous, size-dependent, and label-free manner. Using a small amount of biocompatible polymer as the additive into the media to control the viscoelastic forces exerted on EVs, we are able to achieve a high separation purity (>90%) and recovery (>80%) of exosomes. The size cutoff in viscoelasticity-based microfluidics can be easily controlled using different PEO concentrations. Based on this size-dependent viscoelastic separation strategy, we envision the handling of diverse nanoscale objects, such as gold nanoparticles, DNA origami structures, and quantum dots. This work was supported financially by National Natural Science Foundation of China (11572334, 91543125).

  4. HIV and mature dendritic cells: Trojan exosomes riding the Trojan horse?

    National Research Council Canada - National Science Library

    Izquierdo-Useros, Nuria; Naranjo-Gómez, Mar; Erkizia, Itziar; Puertas, Maria Carmen; Borràs, Francesc E; Blanco, Julià; Martinez-Picado, Javier

    2010-01-01

    ...). The Trojan exosome hypothesis proposes that retroviruses can take advantage of the cell-encoded intercellular vesicle traffic and exosome exchange pathway, moving between cells in the absence...

  5. Problem-based learning research in anesthesia teaching: current status and future perspective.

    Science.gov (United States)

    Chilkoti, G; Mohta, M; Wadhwa, R; Saxena, A K

    2014-01-01

    The teaching curriculum in anesthesia involves traditional teaching methods like topic-based didactic lectures, seminars, and journal clubs; intraoperative apprenticeship; and problem-based learning (PBL) and simulation. The advantages of incorporating PBL in anesthesia teaching include development of skills like clinical reasoning, critical thinking, and self-directed learning; in addition it also helps in developing a broader perspective of case scenarios. The present paper discusses the characteristics, key elements, and goals of PBL; various PBL methods available; lacunae in the existing knowledge of PBL research; its current status and future perspectives in anesthesia teaching.

  6. Problem-Based Learning Research in Anesthesia Teaching: Current Status and Future Perspective

    Science.gov (United States)

    Chilkoti, G.; Mohta, M.; Wadhwa, R.; Saxena, A. K.

    2014-01-01

    The teaching curriculum in anesthesia involves traditional teaching methods like topic-based didactic lectures, seminars, and journal clubs; intraoperative apprenticeship; and problem-based learning (PBL) and simulation. The advantages of incorporating PBL in anesthesia teaching include development of skills like clinical reasoning, critical thinking, and self-directed learning; in addition it also helps in developing a broader perspective of case scenarios. The present paper discusses the characteristics, key elements, and goals of PBL; various PBL methods available; lacunae in the existing knowledge of PBL research; its current status and future perspectives in anesthesia teaching. PMID:24982673

  7. Exosomes as agents of change in the cardiovascular system.

    Science.gov (United States)

    Poe, A J; Knowlton, A A

    2017-10-01

    Exosomes have an evolving role in paracrine and autocrine signaling, which is enhanced because these lipid vesicles are quite stable and can deliver miRNA, DNA, protein and other molecules to cells throughout the body. Most cell types release exosomes, and exosomes are found in all biological fluids, making them accessible biomarkers. Significantly, exosomes can carry a biologically potent cargo, which can alter the phenotype of recipient cells. In the cardiovascular system exosomes have been primarily studied for their role in mediating the beneficial effects of mesenchymal stem cells after myocardial injury. Exosomes released by cardiac cells in disease states, such as myocardial ischemia, can potentially have important pathophysiologic effects on other cardiac cells as well as on distant organs. Published by Elsevier Ltd.

  8. Proteomic Profiling of Exosomes Leads to the Identification of Novel Biomarkers for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Duijvesz, Diederick; Burnum-Johnson, Kristin E.; Gritsenko, Marina A.; Hoogland, Marije; Vredenbregt-van den Berg, Mirella S.; Willemsen, Rob; Luider, Theo N.; Pasa-Tolic, Ljiljana; Jenster, Guido

    2013-12-31

    Introduction: Current markers for prostate cancer, such as PSA lack specificity. Therefore, novel biomarkers are needed. Unfortunately, biomarker discovery from body fluids is often hampered by the high abundance of many proteins unrelated to disease. An attractive alternative biomarker discovery approach is the isolation of small vesicles (exosomes, ~100 nm). They contain proteins that are specific to the tissue from which they are derived and therefore can be considered as treasure chests for disease-specific marker discovery. Profiling prostate cancer-derived exosomes could reveal new markers for this malignancy. Materials and Methods: Exosomes were isolated from 2 immortalized primary prostate epithelial cells (PNT2C2 and RWPE-1) and 2 PCa cell lines (PC346C and VCaP) by ultracentrifugation. Proteomic analyses utilized a nanoLC coupled with an LTQ-Orbitrap operated in tandem MS (MS/MS) mode, followed by the Accurate Mass and Time (AMT) tag approach. Exosomal proteins were validated by Western blotting. A Tissue Micro Array, containing 481 different PCa samples (radical prostatectomy), was used to correlate candidate markers with several clinical-pathological parameters such as PSA, Gleason score, biochemical recurrence, and (PCa-related) death. Results: Proteomic characterization resulted in the identification of 263 proteins by at least 2 peptides. Specifically analysis of exosomes from PNT2C2, RWPE-1, PC346C, and VCaP identified 248, 233, 169, and 216 proteins, respectively. Statistical analyses revealed 52 proteins differently expressed between PCa and control cells, 9 of which were more abundant in PCa. Validation by Western blotting confirmed a higher abundance of FASN, XPO1 and PDCD6IP (ALIX) in PCa exosomes. The Tissue Micro 4 Array showed strong correlation of higher Gleason scores and local recurrence with increased cytoplasmic XPO1 (P<0.001). Conclusions: Differentially abundant proteins of cell line-derived exosomes make a clear subdivision between

  9. Exosomes in Tumor Microenvironment Influence Cancer Progression and Metastasis

    OpenAIRE

    Kahlert, Christoph; Kalluri, Raghu

    2013-01-01

    Exosomes are small membrane vesicles of endocytic origin with a size of 50 – 100 nm. They can contain microRNAs, mRNAs, DNA fragments and proteins, which are shuttled from a donar cell to recipient cells. Many different cell types including immune cells, mesenchymal cells and cancer cells release exosomes. There is emerging evidence that cancer-derived exosomes contribute to the recruitment and reprogramming of constituents associated with tumor environment. Here, we discuss different mechani...

  10. Exosome-Based Cell-Cell Communication in the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Joana Maia

    2018-02-01

    Full Text Available Tumors are not isolated entities, but complex systemic networks involving cell-cell communication between transformed and non-transformed cells. The milieu created by tumor-associated cells may either support or halt tumor progression. In addition to cell-cell contact, cells communicate through secreted factors via a highly complex system involving characteristics such as ligand concentration, receptor expression and integration of diverse signaling pathways. Of these, extracellular vesicles, such as exosomes, are emerging as novel cell-cell communication mediators in physiological and pathological scenarios. Exosomes, membrane vesicles of endocytic origin released by all cells (both healthy and diseased, ranging in size from 30 to 150 nm, transport all the main biomolecules, including lipids, proteins, DNAs, messenger RNAs and microRNA, and perform intercellular transfer of components, locally and systemically. By acting not only in tumor cells, but also in tumor-associated cells such as fibroblasts, endothelium, leukocytes and progenitor cells, tumor- and non-tumor cells-derived exosomes have emerged as new players in tumor growth and invasion, tumor-associated angiogenesis, tissue inflammation and immunologic remodeling. In addition, due to their property of carrying molecules from their cell of origin to the peripheral circulation, exosomes have been increasingly studied as sources of tumor biomarkers in liquid biopsies. Here we review the current literature on the participation of exosomes in the communication between tumor and tumor-associated cells, highlighting the role of this process in the setup of tumor microenvironments that modulate tumor initiation and metastasis.

  11. Simplified protocol for flow cytometry analysis of fluorescently labeled exosomes and microvesicles using dedicated flow cytometer

    Science.gov (United States)

    Pospichalova, Vendula; Svoboda, Jan; Dave, Zankruti; Kotrbova, Anna; Kaiser, Karol; Klemova, Dobromila; Ilkovics, Ladislav; Hampl, Ales; Crha, Igor; Jandakova, Eva; Minar, Lubos; Weinberger, Vit; Bryja, Vitezslav

    2015-01-01

    Flow cytometry is a powerful method, which is widely used for high-throughput quantitative and qualitative analysis of cells. However, its straightforward applicability for extracellular vesicles (EVs) and mainly exosomes is hampered by several challenges, reflecting mostly the small size of these vesicles (exosomes: ~80–200 nm, microvesicles: ~200–1,000 nm), their polydispersity, and low refractive index. The current best and most widely used protocol for beads-free flow cytometry of exosomes uses ultracentrifugation (UC) coupled with floatation in sucrose gradient for their isolation, labeling with lipophilic dye PKH67 and antibodies, and an optimized version of commercial high-end cytometer for analysis. However, this approach requires an experienced flow cytometer operator capable of manual hardware adjustments and calibration of the cytometer. Here, we provide a novel and fast approach for quantification and characterization of both exosomes and microvesicles isolated from cell culture media as well as from more complex human samples (ascites of ovarian cancer patients) suitable for multiuser labs by using a flow cytometer especially designed for small particles, which can be used without adjustments prior to data acquisition. EVs can be fluorescently labeled with protein-(Carboxyfluoresceinsuccinimidyl ester, CFSE) and/or lipid- (FM) specific dyes, without the necessity of removing the unbound fluorescent dye by UC, which further facilitates and speeds up the characterization of microvesicles and exosomes using flow cytometry. In addition, double labeling with protein- and lipid-specific dyes enables separation of EVs from common contaminants of EV preparations, such as protein aggregates or micelles formed by unbound lipophilic styryl dyes, thus not leading to overestimation of EV numbers. Moreover, our protocol is compatible with antibody labeling using fluorescently conjugated primary antibodies. The presented methodology opens the possibility for

  12. Killer B Lymphocytes and their Fas Ligand Positive Exosomes as Inducers of Immune Tolerance

    Directory of Open Access Journals (Sweden)

    Steven Karl Lundy

    2015-03-01

    Full Text Available Induction of immune tolerance is a key process by which the immune system is educated to modulate reactions against benign stimuli such as self-antigens and commensal microbes. Understanding and harnessing the natural mechanisms of immune tolerance may become an increasingly useful strategy for treating many types of allergic and autoimmune diseases, as well as for improving the acceptance of solid organ transplants. Our laboratory and others have been interested in the natural ability of some B lymphocytes to express the death-inducing molecule Fas ligand (FasL, and their ability to kill T helper (TH lymphocytes. We have recently shown that experimental transformation of human B cells by a non-replicative variant of Epstein-Barr virus (EBV consistently resulted in high expression of functional FasL protein. The production and release of FasL+ exosomes that co-expressed MHC Class II molecules and had the capacity to kill antigen-specific TH cells was also observed. Several lines of evidence indicate that FasL+ B cells and FasL+MHCII+ exosomes have important roles in natural immune tolerance and have a great deal of therapeutic potential. Taken together, these findings suggest that EBV-immortalized human B lymphoblastoid cell lines could be used as cellular factories for FasL+ exosomes, which would be employed to therapeutically establish and/or regain immune tolerance toward specific antigens. The goals of this review are to summarize current knowledge of the roles of FasL+ B cells and exosomes in immune regulation, and to suggest methods of manipulating killer B cells and FasL+ exosomes for clinical purposes.

  13. Transcranial direct current stimulation of the right temporoparietal junction impairs third-person perspective taking.

    Science.gov (United States)

    van Elk, Michiel; Duizer, Monique; Sligte, Ilja; van Schie, Hein

    2017-02-01

    Given the current debates about the precise functional role of the right temporoparietal junction (rTPJ) in egocentric and exocentric perspective taking, in the present study we manipulated activity in the rTPJ to investigate the effects on a spatial perspective-taking task. Participants engaged in a mental body transformation task, requiring them to mentally rotate their own body to the position of an avatar, while undergoing anodal, cathodal, or sham transcranial direct current stimulation (tDCS) of the rTPJ. As a control task, participants judged the laterality of a stimulus feature with respect to a fixation cross on the screen. For the first half of the experiment (only during online tDCS), a task-selective effect of tDCS was observed, reflected in slower reaction times following anodal than following cathodal and sham tDCS for the mental body transformation task, but not for the control task. The effects of tDCS were most pronounced for stimuli implying a more difficult mental body transformation. No effects of tDCS were observed during the second half of the experiment. The effects of tDCS were most pronounced for participants scoring low on aberrant perceptual beliefs and spiritual transcendence, suggesting a relation between third-person perspective taking and bodily and perceptual experiences. The finding that anodal stimulation of the rTPJ impairs third-person perspective taking indicates a key role of this region in exocentric spatial processing.

  14. Exosomal tetraspanins mediate cancer metastasis by altering host microenvironment.

    Science.gov (United States)

    Lu, Jun; Li, Jun; Liu, Shuo; Wang, Teng; Ianni, Alessandro; Bober, Eva; Braun, Thomas; Xiang, Rong; Yue, Shijing

    2017-09-22

    The metastases of malignant tumors develop through a cascade of events. The establishment of a pre-metastatic micro-environment is initiated by communication between tumors and host. Exosomes come into focus as the most potent intercellular communicators playing a pivotal role in this process. Cancer cells release exosomes into the extracellular environment prior to metastasis. Tetraspanin is a type of 4 times transmembrane proteins. It may be involved in cell motility, adhesion, morphogenesis, as well as cell and vesicular membrane fusion. The exosomal tetraspanin network is a molecular scaffold connecting various proteins for signaling transduction. The complex of tetraspanin-integrin determines the recruiting cancer exosomes to pre-metastatic sites. Tetraspanin is a key element for the target cell selection of exosomes uptake that may lead to the reprogramming of target cells. Reprogrammed target cells assist pre-metastatic niche formation. Previous reviews have described the biogenesis, secretion and intercellular interaction of exosomes in various tumors. However, there is a lack of reviews on the topic of exosomal tetraspanin in the context of cancer. In this review, we will describe the main characteristics of exosomal tetraspanin in cancer cells. We will also discuss how the cancer exosomal tetraspanin alters extracellular environment and regulates cancer metastasis.

  15. Exosomes from eosinophils autoregulate and promote eosinophil functions.

    Science.gov (United States)

    Cañas, José Antonio; Sastre, Beatriz; Mazzeo, Carla; Fernández-Nieto, Mar; Rodrigo-Muñoz, José Manuel; González-Guerra, Andrés; Izquierdo, Manuel; Barranco, Pilar; Quirce, Santiago; Sastre, Joaquín; Del Pozo, Victoria

    2017-05-01

    Eosinophils are able to secrete exosomes that have an undefined role in asthma pathogenesis. We hypothesized that exosomes released by eosinophils autoregulate and promote eosinophil function. Eosinophils of patients with asthma (n = 58) and healthy volunteers (n = 16) were purified from peripheral blood, and exosomes were isolated and quantified from eosinophils of the asthmatic and healthy populations. Apoptosis, adhesion, adhesion molecules expression, and migration assays were performed with eosinophils in the presence or absence of exosomes from healthy and asthmatic individuals. Reactive oxygen species (ROS) were evaluated by flow cytometry with an intracellular fluorescent probe and nitric oxide (NO) and a colorimetric kit. In addition, exosomal proteins were analyzed by mass spectrometry. Eosinophil-derived exosomes induced an increase in NO and ROS production on eosinophils. Moreover, exosomes could act as a chemotactic factor on eosinophils, and they produced an increase in cell adhesion, giving rise to a specific augmentation of adhesion molecules, such as ICAM-1 and integrin α2. Protein content between exosomes from healthy and asthmatic individuals seems to be similar in both groups. In conclusion, we found that exosomes from the eosinophils of patients with asthma could modify several specific eosinophil functions related to asthma pathogenesis and that they could contribute fundamentally to the development and maintenance of asthma. © Society for Leukocyte Biology.

  16. Characteristics and Roles of Exosomes in Cardiovascular Disease.

    Science.gov (United States)

    Zhang, Yuan; Hu, Yan-Wei; Zheng, Lei; Wang, Qian

    2017-03-01

    Exosomes are nano-sized biological membrane-enclosed vesicles that contain a cell-specific cargo of proteins, lipids, and nucleic acids that are released and taken up by most cell types, thereby inducing expression and functional changes via horizontal transfer of cargos between cells. Thus, exosomes present a largely unknown "cell-to-cell" communication system, which is now increasingly being investigated for diagnostic and therapeutic use in cardiovascular disease (CVD). The purpose of this review is to summarize recent findings on the properties and roles of exosomes in a variety of physiological and pathological settings related to CVD. We focus on available information on exosome-mediated intercellular communication relevant to myocardial injury, repair, and regeneration. Finally, we address the promise of exosomes as valuable diagnostic and prognostic biomarkers, and their potential use as therapeutic tools in CVD. Exosomes remain largely unexplored for therapeutic use in the field of cardiovascular diagnosis and medicine. A more detailed characterization of cardiac exosomes shed by different components of the heart will be of fundamental importance to address specific changes in the profile of exosomal microRNAs and proteins, which will enable the clinical use of exosomes as minimally invasive diagnostic tools and vehicles for delivery of targeted therapies for CVD.

  17. Exosomes in cancer theranostic: Diamonds in the rough.

    Science.gov (United States)

    Cordonnier, Marine; Chanteloup, Gaëtan; Isambert, Nicolas; Seigneuric, Renaud; Fumoleau, Pierre; Garrido, Carmen; Gobbo, Jessica

    2017-03-04

    During the last 10 years, exosomes, which are small vesicles of 50-200 nm diameter of endosomal origin, have aroused a great interest in the scientific and clinical community for their roles in intercellular communication in almost all physiological and pathological processes. Most cells can potentially release these nanovesicles that share with the parent cell a similar lipid bilayer with transmembrane proteins and a panel of enclosed soluble proteins such as heat shock proteins and genetic material, thus acting as potential nanoshuttles of biomarkers. Exosomes surface proteins allow their targeting and capture by recipient cells, while the exosomes' content can modify the physiological state of recipient cells. Tumor derived exosomes by interacting with other cells of the tumor microenvironment modulate tumor progression, angiogenic switch, metastasis, and immune escape. Targeting tumor-derived exosomes might be an interesting approach in cancer therapy. Furthermore, because a key issue to improve cancer patients' outcome relies on earlier cancer diagnosis (metastases, as opposed to the primary tumor, are responsible for most cancer deaths) exosomes have been put forward as promising biomarker candidates for cancer diagnosis and prognosis. This review summarizes the roles of exosomes in cancer and clinical interest, focusing on the importance of exosomal heat shock proteins (HSP). The challenges of clinical translation of HSP-exosomes as therapeutic targets and biomarkers for early cancer detection are also discussed.

  18. Exosomes: From Garbage Bins to Promising Therapeutic Targets.

    Science.gov (United States)

    H Rashed, Mohammed; Bayraktar, Emine; K Helal, Gouda; Abd-Ellah, Mohamed F; Amero, Paola; Chavez-Reyes, Arturo; Rodriguez-Aguayo, Cristian

    2017-03-02

    Intercellular communication via cell-released vesicles is a very important process for both normal and tumor cells. Cell communication may involve exosomes, small vesicles of endocytic origin that are released by all types of cells and are found in abundance in body fluids, including blood, saliva, urine, and breast milk. Exosomes have been shown to carry lipids, proteins, mRNAs, non-coding RNAs, and even DNA out of cells. They are more than simply molecular garbage bins, however, in that the molecules they carry can be taken up by other cells. Thus, exosomes transfer biological information to neighboring cells and through this cell-to-cell communication are involved not only in physiological functions such as cell-to-cell communication, but also in the pathogenesis of some diseases, including tumors and neurodegenerative conditions. Our increasing understanding of why cells release exosomes and their role in intercellular communication has revealed the very complex and sophisticated contribution of exosomes to health and disease. The aim of this review is to reveal the emerging roles of exosomes in normal and pathological conditions and describe the controversial biological role of exosomes, as it is now understood, in carcinogenesis. We also summarize what is known about exosome biogenesis, composition, functions, and pathways and discuss the potential clinical applications of exosomes, especially as biomarkers and novel therapeutic agents.

  19. Development of exosome surface display technology in living human cells.

    Science.gov (United States)

    Stickney, Zachary; Losacco, Joseph; McDevitt, Sophie; Zhang, Zhiwen; Lu, Biao

    2016-03-25

    Surface display technology is an emerging key player in presenting functional proteins for targeted drug delivery and therapy. Although a number of technologies exist, a desirable mammalian surface display system is lacking. Exosomes are extracellular vesicles that facilitate cell-cell communication and can be engineered as nano-shuttles for cell-specific delivery. In this study, we report the development of a novel exosome surface display technology by exploiting mammalian cell secreted nano-vesicles and their trans-membrane protein tetraspanins. By constructing a set of fluorescent reporters for both the inner and outer surface display on exosomes at two selected sites of tetraspanins, we demonstrated the successful exosomal display via gene transfection and monitoring fluorescence in vivo. We subsequently validated our system by demonstrating the expected intracellular partitioning of reporter protein into sub-cellular compartments and secretion of exosomes from human HEK293 cells. Lastly, we established the stable engineered cells to harness the ability of this robust system for continuous production, secretion, and uptake of displayed exosomes with minimal impact on human cell biology. In sum, our work paved the way for potential applications of exosome, including exosome tracking and imaging, targeted drug delivery, as well as exosome-mediated vaccine and therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Development of exosome surface display technology in living human cells

    Energy Technology Data Exchange (ETDEWEB)

    Stickney, Zachary, E-mail: zstickney@scu.edu; Losacco, Joseph, E-mail: jlosacco@scu.edu; McDevitt, Sophie, E-mail: smmcdevitt@scu.edu; Zhang, Zhiwen, E-mail: zzhang@scu.edu; Lu, Biao, E-mail: blu2@scu.edu

    2016-03-25

    Surface display technology is an emerging key player in presenting functional proteins for targeted drug delivery and therapy. Although a number of technologies exist, a desirable mammalian surface display system is lacking. Exosomes are extracellular vesicles that facilitate cell–cell communication and can be engineered as nano-shuttles for cell-specific delivery. In this study, we report the development of a novel exosome surface display technology by exploiting mammalian cell secreted nano-vesicles and their trans-membrane protein tetraspanins. By constructing a set of fluorescent reporters for both the inner and outer surface display on exosomes at two selected sites of tetraspanins, we demonstrated the successful exosomal display via gene transfection and monitoring fluorescence in vivo. We subsequently validated our system by demonstrating the expected intracellular partitioning of reporter protein into sub-cellular compartments and secretion of exosomes from human HEK293 cells. Lastly, we established the stable engineered cells to harness the ability of this robust system for continuous production, secretion, and uptake of displayed exosomes with minimal impact on human cell biology. In sum, our work paved the way for potential applications of exosome, including exosome tracking and imaging, targeted drug delivery, as well as exosome-mediated vaccine and therapy.

  1. Exosomes Derived From Natural Killer Cells Exert Therapeutic Effect in Melanoma.

    Science.gov (United States)

    Zhu, Liya; Kalimuthu, Senthilkumar; Gangadaran, Prakash; Oh, Ji Min; Lee, Ho Won; Baek, Se Hwan; Jeong, Shin Young; Lee, Sang-Woo; Lee, Jaetae; Ahn, Byeong-Cheol

    2017-01-01

    imaging system and ultrasound imaging. Tumor mass was monitored after in vivo experiments. Results: RT-PCR and western blotting confirmed effluc gene expression and protein levels in B16F10/effluc cells. B16F10/effluc activity was found to increase with increasing cell numbers, using BLI assay. For NK-92 Exo characterization, western blotting was performed on both ultracentrifuged and density gradient-isolated exosomes. The results confirmed that NK cell-derived exosomes express two typical exosome proteins, namely CD63 and ALIX. We demonstrated by western blot analysis that NK-92 Exo presented two functional NK proteins, namely perforin and FasL. Moreover, we confirmed the membrane expression of FasL. The enzyme-linked immunosorbent assay results indicated that NK-92 Exo can secrete tumor necrosis factor (TNF)-α, which affected the cell proliferation signaling pathway. The antitumor effect of NK-92 Exo against B16F10/effluc cells in vitro was confirmed by BLI (p < 0.001) and CCK-8 assays (p < 0.001). Furthermore, in normal healthy cells, even after 24 h of co-culture, NK-92 Exo did not exhibit significant side effects. In the in vivo experiments, tumors in the vehicle control group were significantly increased, compared with those in the NK-92 Exo-treated group (p < 0.05). Conclusion: The results of the current study suggest that exosomes derived from NK cells exert cytotoxic effects on melanoma cells and thus warrant further development as a potential immunotherapeutic strategy for cancer.

  2. Label-free Proteomic Analysis of Exosomes Derived from Inducible Hepatitis B Virus-Replicating HepAD38 Cell Line.

    Science.gov (United States)

    Jia, Xiaofang; Chen, Jieliang; Megger, Dominik A; Zhang, Xiaonan; Kozlowski, Maya; Zhang, Lijun; Fang, Zhong; Li, Jin; Chu, Qiaofang; Wu, Min; Li, Yaming; Sitek, Barbara; Yuan, Zhenghong

    2017-04-01

    proteasome subunit proteins by HepAD38 (dox(-))-exo might modulate the production of pro-inflammatory molecules in the recipient monocytes. These results revealed the composition and potential function of exosomes produced during HBV replication, thus providing a new perspective on the role of exosomes in HBV-host interaction. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Cytosolic YB-1 and NSUN2 are the only proteins recognizing specific motifs present in mRNAs enriched in exosomes.

    Science.gov (United States)

    Kossinova, Olga A; Gopanenko, Alexander V; Tamkovich, Svetlana N; Krasheninina, Olga A; Tupikin, Alexey E; Kiseleva, Elena; Yanshina, Darya D; Malygin, Alexey A; Ven'yaminova, Alia G; Kabilov, Marsel R; Karpova, Galina G

    2017-06-01

    Exosomes, membranous vesicles secreted by various cells, are involved in intercellular communication and carry vast repertoires of RNAs and proteins. Processes mediating RNA sorting into exosomes are currently poorly understood. Using bioinformatics approaches, three structural motifs ACCAGCCU, CAGUGAGC and UAAUCCCA have been discovered as enriched in exosomal mRNAs and long noncoding RNAs. Here, utilizing short RNA hairpins, each containing one of the motifs, in a pull-down assay of cytosolic extract of human embryonic kidney 293 (HEK293) cells, we prove that multifunctional RNA-binding protein YB-1 specifically interacts with all three motifs, whereas methyltransferase NSUN2 recognizes only the motif CAGUGAGC. RNA hairpins other than those mentioned above pull out neither YB-1 nor NSUN2. Both these proteins are found in exosomes secreted by HEK293 cells. YB-1 for all that is detected as a form having a slightly higher electrophoretic mobility than that of YB-1 associated with the above RNA hairpins, assuming changes in posttranslational modifications of the protein during its transfer from cytoplasm into exosomes. Next generation sequencing of total exosomal RNA (eRNA) reveals a large representative set of RNA species, including mRNAs containing the above-mentioned motifs. The degree of enrichment in exosomes with this kind of mRNAs strongly depends on the locations of eRNA-specific motifs within the mRNA sequences. Altogether, our findings point to YB-1 and NSUN2 as possible mediators of the process of transfer of specific mRNAs into exosomes, allowing us to speculate on an involvement of these proteins in the mRNA sorting via the recognition of the above motifs. Copyright © 2017. Published by Elsevier B.V.

  4. Perspective: Improving Nutritional Guidelines for Sustainable Health Policies: Current Status and Perspectives.

    Science.gov (United States)

    Magni, Paolo; Bier, Dennis M; Pecorelli, Sergio; Agostoni, Carlo; Astrup, Arne; Brighenti, Furio; Cook, Robert; Folco, Emanuela; Fontana, Luigi; Gibson, Robert A; Guerra, Ranieri; Guyatt, Gordon H; Ioannidis, John Pa; Jackson, Ann S; Klurfeld, David M; Makrides, Maria; Mathioudakis, Basil; Monaco, Alessandro; Patel, Chirag J; Racagni, Giorgio; Schünemann, Holger J; Shamir, Raanan; Zmora, Niv; Peracino, Andrea

    2017-07-01

    A large body of evidence supports the notion that incorrect or insufficient nutrition contributes to disease development. A pivotal goal is thus to understand what exactly is appropriate and what is inappropriate in food ingestion and the consequent nutritional status and health. The effective application of these concepts requires the translation of scientific information into practical approaches that have a tangible and measurable impact at both individual and population levels. The agenda for the future is expected to support available methodology in nutrition research to personalize guideline recommendations, properly grading the quality of the available evidence, promoting adherence to the well-established evidence hierarchy in nutrition, and enhancing strategies for appropriate vetting and transparent reporting that will solidify the recommendations for health promotion. The final goal is to build a constructive coalition among scientists, policy makers, and communication professionals for sustainable health and nutritional policies. Currently, a strong rationale and available data support a personalized dietary approach according to personal variables, including sex and age, circulating metabolic biomarkers, food quality and intake frequency, lifestyle variables such as physical activity, and environmental variables including one's microbiome profile. There is a strong and urgent need to develop a successful commitment among all the stakeholders to define novel and sustainable approaches toward the management of the health value of nutrition at individual and population levels. Moving forward requires adherence to well-established principles of evidence evaluation as well as identification of effective tools to obtain better quality evidence. Much remains to be done in the near future. © 2017 American Society for Nutrition.

  5. Perturbations in the Urinary Exosome in Transplant Rejection

    Energy Technology Data Exchange (ETDEWEB)

    Sigdel, Tara K.; NG, Yolanda; Lee, Sangho; Nicora, Carrie D.; Qian, Weijun; Smith, Richard D.; Camp, David G.; Sarwal, Minnie M.

    2015-01-05

    Background: Urine exosomes, vesicles exocytosed into urine by all renal epithelial cell types, occur under normal physiologic and disease states. Exosome contents may mirror disease-specific proteome perturbations in kidney injury. Analysis methodologies for the exosomal fraction of the urinary proteome were developed and for comparing the urinary exosomal fraction versus unfractionated proteome for biomarker discovery. Methods: Urine exosomes were isolated by centrifugal filtration from mid-stream, second morning void, urine samples collected from kidney transplant recipients with and without biopsy matched acute rejection. The proteomes of unfractionated whole urine (Uw) and urine exosomes (Uexo) underwent mass spectrometry-based quantitative proteomics analysis. The proteome data were analyzed for significant differential protein abundances in acute rejection (AR). Results: Identifications of 1018 and 349 proteins, Uw and Uexo fractions, respectively, demonstrated a 279 protein overlap between the two urinary compartments with 25%(70) of overlapping proteins unique to Uexoand represented membrane bound proteins (p=9.31e-7). Of 349 urine exosomal proteins identified in transplant patients 220 were not previously identified in the normal urine exosomal fraction. Uexo proteins (11), functioning in the inflammatory / stress response, were more abundant in patients with biopsy-confirmed acute rejection, 3 of which were exclusive to Uexo. Uexo AR-specific biomarkers (8) were also detected in Uw, but since they were observed at significantly lower abundances in Uw, they were not significant for AR in Uw. Conclusions: A rapid urinary exosome isolation method and quantitative measurement of enriched Uexo proteins was applied. Urine proteins specific to the exosomal fraction were detected either in unfractionated urine (at low abundances) or by Uexo fraction analysis. Perturbed proteins in the exosomal compartment of urine collected from kidney transplant patients were

  6. Enrichment of selective miRNAs in exosomes and delivery of exosomal miRNAs in vitro and in vivo.

    Science.gov (United States)

    Zhang, Duo; Lee, Heedoo; Zhu, Ziwen; Minhas, Jasleen K; Jin, Yang

    2017-01-01

    Exosomes are nanovesicles secreted by cells and contain various molecules including protein, lipid, and DNA/RNA. They are crucial mediators of the intercellular communication and serve as promising vehicles for drug delivery and gene therapy. Recently, accumulating evidence suggests that microRNAs (miRNAs) may serve as new and potentially powerful targets for therapeutic interventions against various human diseases. However, steadily and effectively delivering miRNA mimics or inhibitors to target cells remains a major obstacle. To enhance the efficacy of exosome-mediated delivery of miRNA molecules, it is crucial to develop a convenient and efficient method to enrich specific miRNAs or antisense oligos in isolated exosomes. Here we report a novel method to prepare specific miRNA molecule-loaded exosomes. Using a modified calcium chloride-mediated transfection method, we successfully enhanced the designated miRNA mimics or inhibitors in isolated exosomes directly, instead of transfecting their mother cells. We also compared this method with direct transfection of exosomes using electroporation. Both methods confirmed that exosomes can serve as cargos to deliver a robustly increased amount of selected miRNA mimic(s) or inhibitor(s) to the recipient cells. Delivery of these miRNA molecule enriched-exosomes subsequently results in highly efficient overexpression or deletion of the designated miRNAs in the recipient cells both in vivo and in vitro. Additionally, we confirmed that exosome-delivered miRNA mimics or inhibitors are functional in the recipient cells. Collectively, we developed a novel protocol to conveniently manipulate exosomal miRNAs with high efficiency and successfully deliver the exosomal miRNA molecules to recipient cells. Copyright © 2017 the American Physiological Society.

  7. Interplay between Autophagy, Exosomes and HIV-1 Associated Neurological Disorders: New Insights for Diagnosis and Therapeutic Applications

    Directory of Open Access Journals (Sweden)

    Chet Raj Ojha

    2017-07-01

    Full Text Available The autophagy–lysosomal pathway mediates a degradative process critical in the maintenance of cellular homeostasis as well as the preservation of proper organelle function by selective removal of damaged proteins and organelles. In some situations, cells remove unwanted or damaged proteins and RNAs through the release to the extracellular environment of exosomes. Since exosomes can be transferred from one cell to another, secretion of unwanted material to the extracellular environment in exosomes may have an impact, which can be beneficial or detrimental, in neighboring cells. Exosome secretion is under the influence of the autophagic system, and stimulation of autophagy can inhibit exosomal release and vice versa. Neurons are particularly vulnerable to degeneration, especially as the brain ages, and studies indicate that imbalances in genes regulating autophagy are a common feature of many neurodegenerative diseases. Cognitive and motor disease associated with severe dementia and neuronal damage is well-documented in the brains of HIV-infected individuals. Neurodegeneration seen in the brain in HIV-1 infection is associated with dysregulation of neuronal autophagy. In this paradigm, we herein provide an overview on the role of autophagy in HIV-associated neurodegenerative disease, focusing particularly on the effect of autophagy modulation on exosomal release of HIV particles and how this interplay impacts HIV infection in the brain. Specific autophagy–regulating agents are being considered for therapeutic treatment and prevention of a broad range of human diseases. Various therapeutic strategies for modulating specific stages of autophagy and the current state of drug development for this purpose are also evaluated.

  8. Biodistribution and Delivery Efficiency of Unmodified Tumor-Derived Exosomes

    Science.gov (United States)

    Smyth, Tyson; Kullberg, Max; Malik, Noeen; Smith-Jones, Peter; Graner, Michael W.; Anchordoquy, Thomas J.

    2014-01-01

    The use of exosomes as a drug delivery vehicle has gained considerable interest. To establish if exosomes could be utilized effectively for drug delivery, a better understanding of their in vivo fate must be established. Through comparisons to liposomal formulations, which have been studied extensively for the last thirty years, we were able to make some comprehensive conclusions about the fate of unmodified tumor-derived exosomes in vivo. We observed a comparable rapid clearance and minimal tumor accumulation of intravenously-injected exosomes, PC:Chol liposomes, and liposomes formulated with the lipid extract of exosomes, suggesting the unique protein and lipid composition of exosomes does not appreciably impact exosomes’ rate of clearance and biodistribution. This rapid clearance along with minimal tumor accumulation of unmodified exosomes limits their use as an anti-cancer drug delivery vehicle; however, when delivered intratumorally, exosomes remained associated with tumor tissue to a significantly greater extent than PC:Chol liposomes. Furthermore, experiments utilizing mice with impaired adaptive or innate immune systems, revealed the significance of the innate immune system along with the complement protein C5 on exosomes’ rate of clearance. PMID:25523519

  9. Proteogenomic analysis reveals exosomes are more oncogenic than ectosomes

    Science.gov (United States)

    Liem, Michael; Fonseka, Pamali; Atukorala, Ishara; Ozcitti, Cemil; Mechler, Adam; Adda, Christopher G.; Ang, Ching-Seng; Mathivanan, Suresh

    2015-01-01

    Extracellular vesicles (EVs) include the exosomes (30-100 nm) that are produced through the endocytic pathway via the multivesicular bodies and the ectosomes (100-1000 nm) that are released through the budding of the plasma membrane. Despite the differences in the mode of biogenesis and size, reliable markers that can distinguish between exosomes and ectosomes are non-existent. Moreover, the precise functional differences between exosomes and ectosomes remains poorly characterised. Here, using label-free quantitative proteomics, we highlight proteins that could be exploited as markers to discriminate between exosomes and ectosomes. For the first time, a global proteogenomics analysis unveiled the secretion of mutant proteins that are implicated in cancer progression through tumor-derived EVs. Follow up integrated bioinformatics analysis highlighted the enrichment of oncogenic cargo in exosomes and ectosomes. Interestingly, exosomes induced significant cell proliferation and migration in recipient cells compared to ectosomes confirming the oncogenic nature of exosomes. These findings ascertain that cancer cells facilitate oncogenesis by the secretion of mutant and oncoproteins into the tumor microenvironment via exosomes and ectosomes. The integrative proteogenomics approach utilized in this study has the potential to identify disease biomarker candidates which can be later assayed in liquid biopsies obtained from cancer patients. PMID:25944692

  10. 3D plasmonic nanobowl platform for the study of exosomes in solution

    Science.gov (United States)

    Lee, Changwon; Carney, Randy P.; Hazari, Sidhartha; Smith, Zachary J.; Knudson, Alisha; Robertson, Christopher S.; Lam, Kit S.; Wachsmann-Hogiu, Sebastian

    2015-05-01

    Thin silver film coated nanobowl Surface Enhanced Raman Spectroscopy (SERS) substrates are used to capture exosomes in solution for SERS measurements that can provide biochemical analysis of intact and ruptured exosomes. Exosomes derived via Total Exosome Isolation Reagent (TEIR) as well as ultracentrifugation (UC) from the SKOV3 cell line were analyzed. Spectra of exosomes derived via TEIR are dominated by a signal characteristic for the TEIR kit that needs to be subtracted for all measurements. Differences in SERS spectra recorded at different times during the drying of the exosome solution are statistically analyzed with Principal Component Analysis (PCA). At the beginning of the drying process, SERS spectra of exosomes exhibit peaks characteristic for both lipids and proteins. Later on during the drying process, new SERS peaks develop, suggesting that the initially intact exosome ruptures over time. This time-dependent evolution of SERS peaks enables analysis of exosomal membrane contents and the contents inside the exosomes.

  11. Vaccine industry perspective of current issues of good manufacturing practices regarding product inspections and stability testing.

    Science.gov (United States)

    Monahan, T R

    2001-12-15

    I address 2 important topics of current good manufacturing practices as they apply to vaccine products: product inspections and stability testing. The perspective presented is that of regulated industry. There are 2 major categories of product/facility inspections: those occurring before licensure of a vaccine product and those occurring after a vaccine product is licensed. The logistics and focus of each inspection type, the preapproval inspection, and the required biennial inspection are discussed, as are guidance and recommendations for achieving successful inspections. The requirements, guidance, and recommendations regarding the type, amount, and extensiveness of stability data for vaccine products are presented. The discussion details the potential differences in the amount and type of data required for products that are not yet licensed versus marketed products. Guidance, from a regulated industry perspective, regarding the design and implementation of a successful stability program is also discussed.

  12. Exosomes Derived from Breast Cancer Cells, Small Trojan Horses?

    Science.gov (United States)

    Villagrasa, Alejandro; Álvarez, Pablo Juan; Osuna, Antonio; Garrido, Jose Manuel; Aránega, Antonia; Rodríguez-Serrano, Fernando

    2014-12-01

    Exosomes are small extracellular vesicles secreted to the extracellular environment by several cell types, including tumor cells. It has been demonstrated that exosomes have an important role in intercellular communication, but they have recently been implicated in various tumor processes, including the oncogenic transformation of cells in the tumor microenvironment, tumor drug resistance, and the transport of tumor factors. Tumors appear to use exosomes to dialogue with and transform neighboring cells to create an ideal environment for their growth and expansion. On the other hand, the structure and function of exosomes may make them useful in cancer diagnosis and prognosis, because they contain molecules that could serve as biomarkers, including oncogenes, miRNAs, and certain proteins. They have the ability to travel via body fluids, from which they could be isolated and used to transport drugs to specific targets. This review aims to provide an update on the role of exosomes derived from breast cancer cells.

  13. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.

    NARCIS (Netherlands)

    Buschow, S.I.; Balkom, B.W.M. van; Aalberts, M.; Heck, A.J.R. van; Wauben, M.; Stoorvogel, W.

    2010-01-01

    Professional antigen-presenting cells secrete major histocompatibility complex class II (MHC II) carrying exosomes with unclear physiological function(s). Exosomes are first generated as the intraluminal vesicles (ILVs) of a specific type of multivesicular body, and are then secreted by fusion of

  14. Identification and proteomic analysis of osteoblast-derived exosomes

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Min; Ke, Ronghu; Cai, Tianyi; Yang, Junyi; Mu, Xiongzheng, E-mail: cranio@vip.163.com

    2015-11-06

    Exosomes are nanometer-sized vesicles with the function of intercellular communication, and they are released by various cell types. To reveal the knowledge about the exosomes from osteoblast, and explore the potential functions of osteogenesis, we isolated microvesicles from supernatants of mouse Mc3t3 by ultracentrifugation, characterized exosomes by electron microscopy and immunoblotting and presented the protein profile by proteomic analysis. The result demonstrated that microvesicles were between 30 and 100 nm in diameter, round shape with cup-like concavity and expressed exosomal marker tumor susceptibility gene (TSG) 101 and flotillin (Flot) 1. We identified a total number of 1069 proteins among which 786 proteins overlap with ExoCarta database. Gene Oncology analysis indicated that exosomes mostly derived from plasma membrane and mainly involved in protein localization and intracellular signaling. The Ingenuity Pathway Analysis showed pathways are mostly involved in exosome biogenesis, formation, uptake and osteogenesis. Among the pathways, eukaryotic initiation factor 2 pathways played an important role in osteogenesis. Our study identified osteoblast-derived exosomes, unveiled the content of them, presented potential osteogenesis-related proteins and pathways and provided a rich proteomics data resource that will be valuable for further studies of the functions of individual proteins in bone diseases. - Highlights: • We for the first time identified exosomes from mouse osteoblast. • Osteoblasts-derived exosomes contain osteoblast peculiar proteins. • Proteins from osteoblasts-derived exosomes are intently involved in EIF2 pathway. • EIF2α from the EIF2 pathway plays an important role in osteogenesis.

  15. Long Distance Metabolic Regulation through Adipose-Derived Circulating Exosomal miRNAs: A Trail for RNA-Based Therapies?

    Directory of Open Access Journals (Sweden)

    Farah Fatima

    2017-08-01

    Full Text Available The contribution of non-coding RNAs, such as microRNAs (miRNAs in regulating physiological and pathological states has been intensively elucidated during last 15 years. The discovery of circulating miRNAs (cir-miRNAs in variety of body fluids, is, however a recent focus of interest in understanding pathophysiological states of their originating cells/organs. Yet another stimulating debate that takes miRNAs to the next level is their presence in exosomes, and this is truly interesting area of research. Exosomes are cell-derived extracellular vesicles, and are naturally equipped biological vehicles that not only enable functional transfer of miRNAs between cells (horizontal transfer but also foster inter-organ communication, presumably guided by organ specific receptors—decorated on their surface. However, understandings on inter-organ communication elicited by tissue specific exosomal-miRNA fingerprints remain elusive. Recently, Thomou et al., has discovered that adipose tissue contributes a large fraction of adipose specific exosomal-miRNA fingerprints in blood circulation. Experimental evidence emphasize adipose tissue as major depot of cir-miRNAs that sail through blood flow and reach to distal organs—primarily in the liver, where they regulate gene expression of host tissue and elicit metabolic control. This appears to be a genetic form of adipokines (endocrine factors secreted from adipose tissue. We review such offshore metabolic insults, and make an effort to address few important missing links between miRNAs processing and their incorporation into exosomes. We provide potential perspectives on how this knowledge could be steered towards RNA-based therapeutics for monitoring complex metabolic diseases and beyond.

  16. Long Distance Metabolic Regulation through Adipose-Derived Circulating Exosomal miRNAs: A Trail for RNA-Based Therapies?

    Science.gov (United States)

    Fatima, Farah; Nawaz, Muhammad

    2017-01-01

    The contribution of non-coding RNAs, such as microRNAs (miRNAs) in regulating physiological and pathological states has been intensively elucidated during last 15 years. The discovery of circulating miRNAs (cir-miRNAs) in variety of body fluids, is, however a recent focus of interest in understanding pathophysiological states of their originating cells/organs. Yet another stimulating debate that takes miRNAs to the next level is their presence in exosomes, and this is truly interesting area of research. Exosomes are cell-derived extracellular vesicles, and are naturally equipped biological vehicles that not only enable functional transfer of miRNAs between cells (horizontal transfer) but also foster inter-organ communication, presumably guided by organ specific receptors—decorated on their surface. However, understandings on inter-organ communication elicited by tissue specific exosomal-miRNA fingerprints remain elusive. Recently, Thomou et al., has discovered that adipose tissue contributes a large fraction of adipose specific exosomal-miRNA fingerprints in blood circulation. Experimental evidence emphasize adipose tissue as major depot of cir-miRNAs that sail through blood flow and reach to distal organs—primarily in the liver, where they regulate gene expression of host tissue and elicit metabolic control. This appears to be a genetic form of adipokines (endocrine factors secreted from adipose tissue). We review such offshore metabolic insults, and make an effort to address few important missing links between miRNAs processing and their incorporation into exosomes. We provide potential perspectives on how this knowledge could be steered towards RNA-based therapeutics for monitoring complex metabolic diseases and beyond. PMID:28824444

  17. Current status and future perspectives of accelerator-based x-ray light sources

    Science.gov (United States)

    Tanaka, Takashi

    2017-09-01

    State-of-the-art x-ray light sources are nowadays based on large-scale electron accelerators, because the synchrotron radiation (SR) and x-ray free electron laser (XFEL) radiation generated by high-energy electron beams have many advantages over other alternatives in terms of the wavelength tunability, high brightness and flux, high coherence, flexible polarization states, and so on. This is the reason why SR and XFEL light sources have largely contributed to the evolution of x-ray science. This paper reviews the current status of such accelerator-based x-ray light source facilities and discusses their future perspectives.

  18. Clinicians' perspective of the current diagnostic criteria for myofascial pain syndrome.

    Science.gov (United States)

    Grosman-Rimon, Liza; Clarke, Hance; Chan, Aaron K; Mills, Patricia Branco; Rathbone, Alasdair Timothy Llewelyn; Kumbhare, Dinesh

    2017-01-01

    Myofascial pain syndrome (MPS) is one of the most common chronic musculoskeletal pain disorders. However, MPS is often under-diagnosed. The purpose of this study was to characterize practicing clinicians' perspectives of the current diagnostic criteria for MPS. A cross-sectional study design was used with a self-administered questionnaire. The questionnaire evaluated clinicians' perspective of the current diagnostic criteria for MPS. The sample population (n= 119) consisted of 40% family physicians, 31% physical medicine (PM) and rehabilitation specialists, 11% rheumatologists, 10% emergency room (ER) physicians, and 8% anesthesiologists specializing in chronic pain. Our findings demonstrated that participating clinicians agree that ``point tenderness'' and ``pain reproduction'' are criteria for MPS. In contrast, the clinicians do not consider ``autonomic symptoms'' as an important criterion for MPS. The anesthesiologists view ``restricted range of motion'' as a criterion for MPS more than the other groups, and they tend to consider ``referred pain'' and ``pain reproduction'' as criteria. Physical medicine and rehabilitation specialists and anesthesiologists tend to view ``local twitch response'' more as a criterion for MPS compared with the other groups. Most groups of clinicians consider ``weakness without atrophy'' as an important MPS criterion except for family physicians. It is important to note that ``poor sleep'', ``daytime fatigue'' and ``cognitive symptoms'', which are not considered as MPS symptoms, are often mistaken for MPS among practicing clinicians. Our findings suggest that the diagnostic criteria are not well known, highlighting the need for an expert consensus to determine the importance of each criterion for MPS diagnosis.

  19. Current knowledge and perspectives on biofilm formation: the case of Listeria monocytogenes.

    Science.gov (United States)

    da Silva, Eliane Pereira; De Martinis, Elaine Cristina Pereira

    2013-02-01

    Listeriosis is a rare, serious, and mainly food-borne infection caused by the bacterium Listeria monocytogenes. This food-borne infection primarily affects pregnant women and immunologically compromised individuals. L. monocytogenes is recognized as a problem for the food industry, mainly due to its environmental persistence, attributed in part to its ability to form biofilms. Biofilms are microbial communities adhered to biotic or abiotic surfaces coated by self-produced extracellular polymers. These structures confer protection to bacterial cells and decrease the efficiency of cleaning and disinfection procedures. This article presents a brief review of current perspectives on the formation of biofilms, with emphasis on L. monocytogenes, highlighting the importance of cell-to-cell communication and structural composition of the microbial communities. The techniques currently used to study biofilms and the need to develop new strategies for the prevention and control of biofilm-forming pathogens are also discussed.

  20. New perspectives for leishmaniasis chemotherapy over current anti-leishmanial drugs: a patent landscape.

    Science.gov (United States)

    Machado-Silva, Alice; Guimarães, Pedro Pires Goulart; Tavares, Carlos Alberto Pereira; Sinisterra, Rubén Dario

    2015-03-01

    Although leishmaniasis is estimated to cause the ninth largest disease burden among individual infectious diseases, it is still one of the most neglected diseases in terms of drug development. Current drugs are highly toxic, resistance is common and compliance of patients to treatment is low, as treatment is long and drug price is high. In this review, the authors carried out a patent landscape in search for new perspectives for leishmaniasis therapy. This search encompassed patent documents having priority date between 1994 and 2014. Selected compounds were compared to current anti-leishmanial drugs regarding efficacy and toxicity, when experimental data were available. Most patents related to drugs for leishmaniasis have not been produced by the pharmaceutical industry but rather by public research institutes or by universities, and the majority of the inventions disclosed are still in preclinical phase. There is an urgent need to find new ways of funding research for leishmaniasis drugs, incentivizing product development partnerships and pushing forward innovation.

  1. Clinical proteomics-driven precision medicine for targeted cancer therapy: current overview and future perspectives.

    Science.gov (United States)

    Zhou, Li; Wang, Kui; Li, Qifu; Nice, Edouard C; Zhang, Haiyuan; Huang, Canhua

    2016-01-01

    Cancer is a common disease that is a leading cause of death worldwide. Currently, early detection and novel therapeutic strategies are urgently needed for more effective management of cancer. Importantly, protein profiling using clinical proteomic strategies, with spectacular sensitivity and precision, offer excellent promise for the identification of potential biomarkers that would direct the development of targeted therapeutic anticancer drugs for precision medicine. In particular, clinical sample sources, including tumor tissues and body fluids (blood, feces, urine and saliva), have been widely investigated using modern high-throughput mass spectrometry-based proteomic approaches combined with bioinformatic analysis, to pursue the possibilities of precision medicine for targeted cancer therapy. Discussed in this review are the current advantages and limitations of clinical proteomics, the available strategies of clinical proteomics for the management of precision medicine, as well as the challenges and future perspectives of clinical proteomics-driven precision medicine for targeted cancer therapy.

  2. Exosomes: novel effectors of human platelet lysate activity.

    Science.gov (United States)

    Torreggiani, E; Perut, F; Roncuzzi, L; Zini, N; Baglìo, S R; Baldini, N

    2014-09-22

    Despite the popularity of platelet-rich plasma (PRP) and platelet lysate (PL) in orthopaedic practice, the mechanism of action and the effectiveness of these therapeutic tools are still controversial. So far, the activity of PRP and PL has been associated with different growth factors (GF) released during platelet degranulation. This study, for the first time, identifies exosomes, nanosized vesicles released in the extracellular compartment by a number of elements, including platelets, as one of the effectors of PL activity. Exosomes were isolated from human PL by differential ultracentrifugation, and analysed by electron microscopy and Western blotting. Bone marrow stromal cells (MSC) treated with three different exosome concentrations (0.6 μg, 5 μg and 50 μg) showed a significant, dose-dependent increase in cell proliferation and migration compared to the control. In addition, osteogenic differentiation assays demonstrated that exosome concentration differently affected the ability of MSC to deposit mineralised matrix. Finally, the analysis of exosome protein content revealed a higher amount of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) as compared to PL. In regards to RNA content, an enrichment of small RNAs in exosomes as compared to donor platelets has been found. These results suggest that exosomes consistently contribute to PL activity and could represent an advantageous nanodelivery system for cell-free regeneration therapies.

  3. Exosome Proteome of U-87MG Glioblastoma Cells

    Directory of Open Access Journals (Sweden)

    Sohyun Chun

    2016-12-01

    Full Text Available Exosomes are small membrane vesicles between 30 and 100 nm in diameter secreted by many cell types, and are associated with a wide range of physiological and/or pathological processes. Exosomes containing proteins, lipids, mRNA, and microRNA contribute to cell-to-cell communication and cell-to-environment regulation, however, their biological functions are not yet fully understood. In this report, exosomes in the glioblastoma cell line, U-87MG, were isolated and the proteome was investigated. In addition, exosome proteome changes in U-87MG cells exposed to a low temperature were investigated to elucidate whether the exosome proteome could respond to an external stimulus. Cell culture medium was collected, and exosomes were isolated by continuous centrifugation eliminating cell debris, nucleic acids, and other particles. The morphology of exosomes was observed by cryo-tunneling electron microscopy. According to 2-dimensional electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry, certain proteins including collagen type VI alpha 1, putative RNA-binding protein 15B chain A, substrate induced remodeling of the active site regulates HTRA1, coatomer protein complex-subunit beta 2, myosin-heavy chain 1, and keratin-type I cytoskeletal 9 showed differences between the control proteome and the low temperature-exposed proteome.

  4. Exosomes carrying immunoinhibitory proteins and their role in cancer.

    Science.gov (United States)

    Whiteside, T L

    2017-09-01

    Recent emergence of exosomes as information carriers between cells has introduced us to a new previously unknown biological communication system. Multi-directional cross-talk mediated by exosomes carrying proteins, lipids and nucleic acids between normal cells, cells harbouring a pathogen or cancer and immune cells has been instrumental in determining outcomes of physiological as well as pathological conditions. Exosomes play a key role in the broad spectrum of human diseases. In cancer, tumour-derived exosomes carry multiple immunoinhibitory signals, disable anti-tumour immune effector cells and promote tumour escape from immune control. Exosomes delivering negative signals to immune cells in cancer, viral infections, autoimmune or other diseases may interfere with therapy and influence outcome. Exosomes can activate tissue cells to produce inhibitory factors and thus can suppress the host immune responses indirectly. Exosomes also promise to be non-invasive disease biomarkers with a dual capability to provide insights into immune dysfunction as well as disease progression and outcome. © 2017 British Society for Immunology.

  5. Tumor-derived exosomes and their role in cancer progression

    Science.gov (United States)

    Whiteside, Theresa L

    2017-01-01

    Tumor cells actively produce, release and utilize exosomes to promote tumor growth. Mechanisms through which tumor-derived exosomes subserve the tumor are under intense investigation. These exosomes are information carriers, conveying molecular and genetic messages from tumor cells to normal or other abnormal cells residing at close or distant sites. Tumor-derived exosomes are found in all body fluids. Upon the contact with target cells, they alter phenotypic and functional attributes of recipients, reprogramming them into active contributors to angiogenesis, thrombosis, metastasis and immunosuppression. Exosomes produced by tumors carry cargos that in part mimic contents of parent cells and are of potential interest as non-invasive biomarkers of cancer. Their role in inhibiting the host antitumor responses and in mediating drug resistance is important for cancer therapy. Tumor-derived exosomes may interfere with cancer immunotherapy, but they also could serve as adjuvants and antigenic components of antitumor vaccines. Their biological roles in cancer development or progression as well as cancer therapy suggest that tumor-derived exosomes are critical components of oncogenic transformation. PMID:27117662

  6. Exosomes and Their Therapeutic Potentials of Stem Cells

    Directory of Open Access Journals (Sweden)

    Chao Han

    2016-01-01

    Full Text Available Exosomes, a group of vesicles originating from the multivesicular bodies (MVBs, are released into the extracellular space when MVBs fuse with the plasma membrane. Numerous studies indicate that exosomes play important roles in cell-to-cell communication, and exosomes from specific cell types and conditions display multiple functions such as exerting positive effects on regeneration in many tissues. It is widely accepted that the therapeutic potential of stem cells may be mediated largely by the paracrine factors, so harnessing the paracrine effects of stem and progenitor cells without affecting these living, replicating, and potentially pluripotent cell populations is an advantage in terms of safety and complexity. Ascending evidence indicated that exosomes might be the main components of paracrine factors; thus, understanding the role of exosomes in each subtype of stem cells is far-reaching. In this review, we discuss the functions of exosomes from different types of stem cells and emphasize the therapeutic potentials of exosomes, providing an alternative way of developing strategies to cure diseases.

  7. MicroRNAs in Parasitic Helminthiases: Current Status and Future Perspectives.

    Science.gov (United States)

    Cai, Pengfei; Gobert, Geoffrey N; McManus, Donald P

    2016-01-01

    MicroRNAs (miRNAs) play a variety of roles in diverse biological processes at the post-transcriptional regulatory level. Although numerous miRNAs have been identified in parasitic helminths, we still know little about their biological functions. As molecular signatures that can be stably detectable in serum and plasma, worm-derived miRNAs have shown promise as markers for the early detection of particular helminth infections. In addition, host miRNAs are dysregulated during the development of pathology associated with helminthiases and show potential as therapeutic intervention targets. This review discusses the possible biological roles of helminth miRNAs, the prediction of their specific targets, their application in diagnosis and anti-pathology therapy interventions, and the potential functions of miRNAs in extracellular vesicle cargo, such as exosomes, in helminth-host interplay. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. In Vivo Neuroimaging of Exosomes Using Gold Nanoparticles.

    Science.gov (United States)

    Betzer, Oshra; Perets, Nisim; Angel, Ariel; Motiei, Menachem; Sadan, Tamar; Yadid, Gal; Offen, Daniel; Popovtzer, Rachela

    2017-11-28

    Exosomes are emerging as effective therapeutic tools for various pathologies. These extracellular vesicles can bypass biological barriers, including the blood-brain barrier, and can serve as powerful drug and gene therapy transporters. However, the progress of therapy development is impeded by several challenges, including insufficient data on exosome trafficking and biodistribution and the difficulty to image deep brain structures in vivo. Herein, we established a method for noninvasive in vivo neuroimaging and tracking of exosomes, based on glucose-coated gold nanoparticle (GNP) labeling and computed tomography imaging. Labeling of exosomes with the GNPs was achieved directly, as opposed to the typical and less efficient indirect labeling mode through parent cells. On the mechanistic level, we found that the glucose-coated GNPs were uptaken into MSC-derived exosomes via an active, energy-dependent mechanism that is mediated by the glucose transporter GLUT-1 and involves endocytic proteins. Next, we determined optimal parameters of size and administration route; we demonstrated that 5 nm GNPs enabled improved exosome labeling and that intranasal, compared to intravenous, administration led to superior brain accumulation and thus enhanced in vivo neuroimaging. Furthermore, using a mouse model of focal brain ischemia, we noninvasively tracked intranasally administered GNP-labeled exosomes, which showed increased accumulation at the lesion site over 24 h, as compared to nonspecific migration and clearance from control brains over the same period. Thus, this exosome labeling technique can serve as a powerful diagnostic tool for various brain disorders and could potentially enhance exosome-based treatments for neuronal recovery.

  9. Exosomes from uninfected cells activate transcription of latent HIV-1.

    Science.gov (United States)

    Barclay, Robert A; Schwab, Angela; DeMarino, Catherine; Akpamagbo, Yao; Lepene, Benjamin; Kassaye, Seble; Iordanskiy, Sergey; Kashanchi, Fatah

    2017-07-14

    HIV-1 infection causes AIDS, infecting millions worldwide. The virus can persist in a state of chronic infection due to its ability to become latent. We have previously shown a link between HIV-1 infection and exosome production. Specifically, we have reported that exosomes transport viral proteins and RNA from infected cells to neighboring uninfected cells. These viral products could then elicit an innate immune response, leading to activation of the Toll-like receptor and NF-κB pathways. In this study, we asked whether exosomes from uninfected cells could activate latent HIV-1 in infected cells. We observed that irrespective of combination antiretroviral therapy, both short- and long-length viral transcripts were increased in wild-type HIV-1-infected cells exposed to purified exosomes from uninfected cells. A search for a possible mechanism for this finding revealed that the exosomes increase RNA polymerase II loading onto the HIV-1 promoter in the infected cells. These viral transcripts, which include trans-activation response (TAR) RNA and a novel RNA that we termed TAR-gag, can then be packaged into exosomes and potentially be exported to neighboring uninfected cells, leading to increased cellular activation. To better decipher the exosome release pathways involved, we used siRNA to suppress expression of ESCRT (endosomal sorting complex required for transport) proteins and found that ESCRT II and IV significantly control exosome release. Collectively, these results imply that exosomes from uninfected cells activate latent HIV-1 in infected cells and that true transcriptional latency may not be possible in vivo, especially in the presence of combination antiretroviral therapy.

  10. Perturbations in the Urinary Exosome in Transplant Rejection

    Directory of Open Access Journals (Sweden)

    Tara eSigdel

    2015-01-01

    Full Text Available Urine exosomes are small vesicles exocytosed into the urine by all renal epithelial cell types under normal physiologic and disease states. Urine exosomal proteins may mirror disease specific proteome perturbations in kidney injury. Analysis methodologies for the exosomal fraction of the urinary proteome were developed for comparing the urinary exosomal fraction versus unfractionated proteome for biomarker discovery. Urine exosomes were isolated by centrifugal filtration of urine samples collected from kidney transplant patients with and without acute rejection, which were biopsy matched. The proteomes of unfractionated whole urine (Uw and urine exosomes (Ue underwent mass spectroscopy-based quantitative proteonomics analysis. The proteome data were analyzed for significant differential protein abundances in acute rejection (AR. A total of 1018 proteins were identified in Uw and 349 proteins in Ue. 279 overlapped between the two urinary compartments and 70 proteins were unique to the Ue compartment. Of 349 exosomal proteins identified from transplant patients,220 had not been previously identified in the normal Ue fraction. 11 Ue proteins, functionally involved in an inflammatory and stress response, were more abundant in urine samples from patients with acute rejection, 3 of which are exclusive to the Ue fraction. Ue AR-specific biomarkers(8 were also detected in Uw, but since they were observed at significantly lower abundances in Uw, they were not significant for AR in Uw. A rapid urinary exosome isolation method and quantitative measurement of enriched Ue proteins was applied. Perturbed proteins in the exosomal compartment of urine collected from kidney transplant patients were specific to inflammatory responses, and were not observed in the Ue fraction from normal healthy subjects. Ue specific protein alterations in renal disease provide potential mechanistic insights and offer a unique panel of sensitive biomarkers for monitoring AR.

  11. HIF-1-mediated production of exosomes during hypoxia is protective in renal tubular cells.

    Science.gov (United States)

    Zhang, Wei; Zhou, Xiangjun; Yao, Qisheng; Liu, Yutao; Zhang, Hao; Dong, Zheng

    2017-10-01

    Exosomes are nano-sized vesicles produced and secreted by cells to mediate intercellular communication. The production and function of exosomes in kidney tissues and cells remain largely unclear. Hypoxia is a common pathophysiological condition in kidneys. This study was designed to characterize exosome production during hypoxia of rat renal proximal tubular cells (RPTCs), investigate the regulation by hypoxia-inducible factor-1 (HIF-1), and determine the effect of the exosomes on ATP-depletion-induced tubular cell injury. Hypoxia did not change the average sizes of exosomes secreted by RPTCs, but it significantly increased exosome production in a time-dependent manner. HIF-1 induction with dimethyloxalylglycine also promoted exosome secretion, whereas pharmacological and genetic suppression of HIF-1 abrogated the increase of exosome secretion under hypoxia. The exosomes from hypoxic RPTCs had inhibitory effects on apoptosis of RPTCs following ATP depletion. The protective effects were lost in the exosomes from HIF-1α knockdown cells. It is concluded that hypoxia stimulates exosome production and secretion in renal tubular cells. The exosomes from hypoxic cells are protective against renal tubular cell injury. HIF-1 mediates exosome production during hypoxia and contributes to the cytoprotective effect of the exosomes. Copyright © 2017 the American Physiological Society.

  12. Exosomes or microvesicles? Two kinds of extracellular vesicles with different routes to modify protozoan-host cell interaction.

    Science.gov (United States)

    Evans-Osses, Ingrid; Reichembach, Luis H; Ramirez, Marcel I

    2015-10-01

    Parasite-host cell interaction can be modulated by a dynamic communication between extracellular vesicles (EVs). They should play key roles in cell-cell communications transferring biomolecules (miRNA, proteins, soluble factors) from one cell to another cell. While many names have been used to denominate EVs, a better comprehension to understand these vesicles is raised when we classify it according to biogenesis: originated from multivesicular bodies, named exosomes, and from plasmatic membranes, denominated microvesicles. Here, we have reviewed EV participation during the protozoan-host cell interaction and reinforced the differences and similarities between exosomes and microvesicles, suggesting different intracellular routes and functions. We also discussed perspectives to study EVs and the role of EVs in diagnosis and chemotherapies of infectious diseases.

  13. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.

    Science.gov (United States)

    Baietti, Maria Francesca; Zhang, Zhe; Mortier, Eva; Melchior, Aurélie; Degeest, Gisèle; Geeraerts, Annelies; Ivarsson, Ylva; Depoortere, Fabienne; Coomans, Christien; Vermeiren, Elke; Zimmermann, Pascale; David, Guido

    2012-06-03

    The biogenesis of exosomes, small secreted vesicles involved in signalling processes, remains incompletely understood. Here, we report evidence that the syndecan heparan sulphate proteoglycans and their cytoplasmic adaptor syntenin control the formation of exosomes. Syntenin interacts directly with ALIX through LYPX(n)L motifs, similarly to retroviral proteins, and supports the intraluminal budding of endosomal membranes. Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs, and impact on the trafficking and confinement of FGF signals. This study identifies a key role for syndecan-syntenin-ALIX in membrane transport and signalling processes.

  14. Research Progress of Exosomes in Lung Cancer Diagnosis and Treatment

    Directory of Open Access Journals (Sweden)

    Hongbo ZOU

    2016-11-01

    Full Text Available As the leading cause of morbidity and cancer related-death worldwide, lung cancer has a serious threat to human health. Exosomes are nanoscale lipid membrane vesicles derived from multivesicles, which containing active biomolecules including proteins, lipids, nucleic acids and etc. Exosomes play important roles in lung cancer initiation and progression by promoting the formation of tumor microenvironment, enhancing tumor invasive and metastasis capability, leading to immunosuppression and resistance to chemoradiotherapy, and also have the application value in early diagnosis and treatment. This review summarizes the research progress of exosomes in tumor initiation and progression, and its roles in diagnosis and treatment of lung cancer.

  15. Interaction profiling identifies the human nuclear exosome targeting complex

    DEFF Research Database (Denmark)

    Lubas, Michal Szymon; Christensen, Marianne Spangsberg; Kristiansen, Maiken Søndergaard

    2011-01-01

    The RNA exosome is a conserved degradation machinery, which obtains full activity only when associated with cofactors. The most prominent activator of the yeast nuclear exosome is the RNA helicase Mtr4p, acting in the context of the Trf4p/Air2p/Mtr4p polyadenylation (TRAMP) complex. The existence...... from nucleoli, and consistently NEXT is specifically required for the exosomal degradation of promoter upstream transcripts (PROMPTs). We also detect putative homolog TRAMP subunits hTRF4-2 (Trf4p) and ZCCHC7 (Air2p) in hRRP6 and hMTR4 precipitates. However, at least ZCCHC7 function is restricted...

  16. Tumour-derived exosomes as a signature of pancreatic cancer - liquid biopsies as indicators of tumour progression.

    Science.gov (United States)

    Nuzhat, Zarin; Kinhal, Vyjayanthi; Sharma, Shayna; Rice, Gregory E; Joshi, Virendra; Salomon, Carlos

    2017-03-07

    Pancreatic cancer is the fourth most common cause of death due to cancer in the world. It is known to have a poor prognosis, mostly because early stages of the disease are generally asymptomatic. Progress in pancreatic cancer research has been slow, leaving several fundamental questions pertaining to diagnosis and treatment unanswered. Recent studies highlight the putative utility of tissue-specific vesicles (i.e. extracellular vesicles) in the diagnosis of disease onset and treatment monitoring in pancreatic cancer. Extracellular vesicles are membrane-limited structures derived from the cell membrane. They contain specific molecules including proteins, mRNA, microRNAs and non-coding RNAs that are secreted in the extracellular space. Extracellular vesicles can be classified according to their size and/or origin into microvesicles (~150-1000 nm) and exosomes (~40-120 nm). Microvesicles are released by budding from the plasmatic membrane, whereas exosomes are released via the endocytic pathway by fusion of multivesicular bodies with the plasmatic membrane. This endosomal origin means that exosomes contain an abundance of cell-specific biomolecules which may act as a 'fingerprint' of the cell of origin. In this review, we discuss our current knowledge in the diagnosis and treatment of pancreatic cancer, particularly the potential role of EVs in these facets of disease management. In particular, we suggest that as exosomes contain cellular protein and RNA molecules in a cell type-specific manner, they may provide extensive information about the signature of the tumour and pancreatic cancer progression.

  17. The human cap-binding complex is functionally connected to the nuclear RNA exosome

    DEFF Research Database (Denmark)

    Andersen, Peter Refsing; Domanski, Michal; Kristiansen, Maiken S

    2013-01-01

    Nuclear processing and quality control of eukaryotic RNA is mediated by the RNA exosome, which is regulated by accessory factors. However, the mechanism of exosome recruitment to its ribonucleoprotein (RNP) targets remains poorly understood. Here we report a physical link between the human exosome...... of combinatorial depletion of CBCN and exosome components underscore the functional relevance of CBC-exosome bridging at the level of target RNA. Specifically, CBCA suppresses read-through products of several RNA families by promoting their transcriptional termination. We suggest that the RNP 5' cap links...... transcription termination to exosomal RNA degradation through CBCN....

  18. Medical radiation countermeasures for nuclear and radiological emergencies: Current status and future perspectives

    Directory of Open Access Journals (Sweden)

    Rajesh Arora

    2010-01-01

    Full Text Available Nuclear and radiological emergencies (NREs occurred globally and recent incidences in India are indicating toward the need for comprehensive medical preparedness required both at incident site and hospitals. The enhanced threat attributed toward insurgency is another causative factor of worry. The response capabilities and operational readiness of responders (both health and non-health service providers in contaminated environment need to be supported by advancement in R & D and technological efforts to develop prophylactics and radiation mitigators. It is essential to develop phase 1 alternatives of such drugs for unseen threats as a part of initial preparedness. At the incident site and hospital level, external decontamination procedures need to be standardized and supported by protective clothing and Shudika kits developed by INMAS. The medical management of exposure requires systematic approach to perform triage, resuscitation and curative care. The internal contamination requires decorporation agents to be administered based on procedural diagnostics. Various key issues pertaining to policy decisions, R & D promotion, community awareness, specialized infrastructure for NREs preparedness has been discussed. The present review is an attempt to provide vital information about the current status of various radiation countermeasures and future perspective(s ahead.

  19. Neuroimaging of attention-deficit/hyperactivity disorder: current neuroscience-informed perspectives for clinicians.

    Science.gov (United States)

    Cortese, Samuele; Castellanos, F Xavier

    2012-10-01

    The neuroimaging literature on attention-deficit/hyperactivity disorder (ADHD) is growing rapidly. Here, we provide a critical overview of neuroimaging studies published recently, highlighting perspectives that may be of relevance for clinicians. After a comprehensive search of PubMed, Ovid, Web of Science, and EMBASE, we located 41 pertinent papers published between January 2011 and April 2012, comprising both structural and functional neuroimaging studies. This literature is increasingly contributing to the notion that the pathophysiology of ADHD reflects abnormal interplay among large-scale brain circuits. Moreover, recent studies have begun to reveal the mechanisms of action of pharmacological treatment. Finally, imaging studies with a developmental perspective are revealing the brain correlates of ADHD over the lifespan, complementing clinical observations on the phenotypic continuity and discontinuity of the disorder. However, despite the increasing potential to eventually inform clinical practice, current imaging studies do not have validated applications in day-to-day clinical practice. Although novel analytical techniques are likely to accelerate the pace of translational applications, at the present we advise caution regarding inappropriate commercial misuse of imaging techniques in ADHD.

  20. Intra-individual variability in tinnitus patients : current thoughts and perspectives.

    Science.gov (United States)

    Dauman, N; Erlandsson, S; Lundlin, L; Dauman, R

    2015-04-01

    Most tinnitus studies have attempted to compare groups of individuals, thus revealing inter-individuals differences, i.e., variations between compared subjects. For methodological reasons, inter-individual studies cannot take into account the variability of tinnitus experience, which has been known for decades to be relevant in daily practice with tinnitus patients. The concept of intra-individual variability has been promoted in the research literature, in order to shed light on this aspect of individual perception. In previous studies, unrelated to hearing, the concept of intra-individual variability implied inclusion of the environment (i.e., physical and social interactions) as a factor of individual performance. In tinnitus research, we believe that the concept of variability (within a person) could find a place beside the concept of variation (between groups of subjects). In this paper, four perspectives of tinnitus experiences from the clinical and research fields are described: (1) ENT consultation; (2) short-term group psychotherapy; (3) psychodynamic psychotherapy; and (4) clinical psychological research. Intra-individual variability stresses the importance of defining tinnitus in a dynamic way, contrary to the current definition of tinnitus as the perception of sound(s). In clinical practice, it is useful to embrace the perspective of the perceiver of tinnitus, and to include social and cultural circumstances as well as audiological/physical changes.

  1. Stem Cells as New Agents for the Treatment of Infertility: Current and Future Perspectives and Challenges

    Directory of Open Access Journals (Sweden)

    Vladislav Volarevic

    2014-01-01

    Full Text Available Stem cells are undifferentiated cells that are present in the embryonic, fetal, and adult stages of life and give rise to differentiated cells that make up the building blocks of tissue and organs. Due to their unlimited source and high differentiation potential, stem cells are considered as potentially new therapeutic agents for the treatment of infertility. Stem cells could be stimulated in vitro to develop various numbers of specialized cells including male and female gametes suggesting their potential use in reproductive medicine. During past few years a considerable progress in the derivation of male germ cells from pluripotent stem cells has been made. In addition, stem cell-based strategies for ovarian regeneration and oocyte production have been proposed as future clinical therapies for treating infertility in women. In this review, we summarized current knowledge and present future perspectives and challenges regarding the use of stem cells in reproductive medicine.

  2. School health education and promotion: current approaches and critical perspectives 2: part 2

    DEFF Research Database (Denmark)

    Leahy, Deana; Simovska, Venka

    2018-01-01

    - The six papers in the special issue draw from a range of critical perspectives to engage with questions of school health education and health promotion, from conceptual historical analyses, to teachers’ views on criticality, to issues of race and culture, to critical sexuality education, and to emotional......Purpose - This Special Issue is the second in a series that aims to place the spotlight on educational research and its contribution to the field of school-based health and wellbeing promotion. The purpose of both special issues is to bring together scholars from across the world to consider...... current developments in research on curricula, interventions, policies and practices concerning health education and promotion and related professional development of teachers. Design/methodology/approach – As in the first Special Issue published in 2017 (School health education and promotion: Health...

  3. Proteomics of Important Food Crops in the Asia Oceania Region: Current Status and Future Perspectives

    KAUST Repository

    Chakraborty, Subhra

    2015-06-02

    In the rapidly growing economies of Asia and Oceania, food security has become a primary concern. With the rising population, growing more food at affordable prices is becoming even more important. In addition, the predicted climate change will lead to drastic changes in global surface temperature and changes in rainfall patterns that in turn would pose a serious threat to plant vegetation worldwide. As a result, understanding how plants will survive in a changing climate will be increasingly important. Such challenges require integrated approaches to increase agricultural production and cope with environmental threats. Proteomics can play a role in unravel the underlying mechanisms for food production to address the growing demand for food. In this review, the current status of food crop proteomics is discussed, especially in regards to the Asia and Oceania regions. Furthermore, the future perspective in relation to proteomic techniques for the important food crops is highlighted.

  4. Advances for prosthetic technology from historical perspective to current status to future application

    CERN Document Server

    LeMoyne, Robert

    2016-01-01

    This book focuses on the advances in transtibial prosthetic technology and targets research in the evolution of the powered prosthesis such as the BiOM, which was derived from considerable research and development at the Massachusetts Institute of Technology. The concept of the book spans the historical evolution of prosthetic applications from passive to new and futuristic robotic prosthetic technologies.  The author describes the reasons for amputation, surgical procedures, and an historical perspective of the prosthesis for the lower limb. He also addresses the phases and sub-phases of gait and compensatory mechanisms arising for a transtibial prosthesis and links the compensatory mechanisms to long-term morbidities.  The general technologies for gait analysis central to prosthetic design and the inherent biomechanics foundations for analysis are also explored.  The book reports on recent-past to current-term applications with passive elastic prostheses.  The core of the book deals with futuristic robo...

  5. Proteomics of Important Food Crops in the Asia Oceania Region: Current Status and Future Perspectives.

    Science.gov (United States)

    Chakraborty, Subhra; Salekdeh, Ghasem Hosseini; Yang, Pingfang; Woo, Sun Hee; Chin, Chiew Foan; Gehring, Chris; Haynes, Paul A; Mirzaei, Mehdi; Komatsu, Setsuko

    2015-07-02

    In the rapidly growing economies of Asia and Oceania, food security has become a primary concern. With the rising population, growing more food at affordable prices is becoming even more important. In addition, the predicted climate change will lead to drastic changes in global surface temperature and changes in rainfall patterns that in turn will pose a serious threat to plant vegetation worldwide. As a result, understanding how plants will survive in a changing climate will be increasingly important. Such challenges require integrated approaches to increase agricultural production and cope with environmental threats. Proteomics can play a role in unraveling the underlying mechanisms for food production to address the growing demand for food. In this review, the current status of food crop proteomics is discussed, especially in regard to the Asia and Oceania regions. Furthermore, the future perspective in relation to proteomic techniques for the important food crops is highlighted.

  6. A Survey of Strategies to Modulate the Bone Morphogenetic Protein Signaling Pathway: Current and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Jonathan W. Lowery

    2016-01-01

    Full Text Available Bone morphogenetic proteins (BMPs constitute the largest subdivision of the TGF-β family of ligands and are unequivocally involved in regulating stem cell behavior. Appropriate regulation of canonical BMP signaling is critical for the development and homeostasis of numerous human organ systems, as aberrations in the BMP pathway or its regulation are increasingly associated with diverse human pathologies. In this review, we provide a wide-perspective on strategies that increase or decrease BMP signaling. We briefly outline the current FDA-approved approaches, highlight emerging next-generation technologies, and postulate prospective avenues for future investigation. We also detail how activating other pathways may indirectly modulate BMP signaling, with a particular emphasis on the relationship between the BMP and Activin/TGF-β pathways.

  7. Genetic Vulnerability as a Distal Risk Factor for Suicidal Behaviour: Historical Perspective and Current Knowledge.

    Science.gov (United States)

    Andriessen, Karl; Videtic-Paska, Alja

    2015-09-01

    Suicide is a multidimensional problem. Observations of family history of suicide suggest the existence of a genetic vulnerability to suicidal behaviour. Starting with a historical perspective, the article reviews current knowledge of a genetic vulnerability to suicidal behaviour, distinct from the genetic vulnerability to psychiatric disorders, focused on clinical and population-based studies, and findings from recent molecular genetics association studies. The review includes peer-reviewed research articles and review papers from the professional literature in English language, retrieved from PubMed/Medline and PsycINFO. The research literature confirms a existence of a genetic vulnerability to suicidal behaviour. Even though the results of individual studies are difficult to compare, genetic influences could explain up to half of the variance of the occurrence of suicide. Genetic vulnerability could be a distal risk factor for suicide, which helps us to understand the occurrence of suicide among vulnerable people. Ethical implications of such vulnerability are highlighted.

  8. Mars atmospheric losses induced by the solar wind: current knowledge and perspective

    Science.gov (United States)

    Ermakov, Vladimir; Zelenyi, Lev; Vaisberg, Oleg; Sementsov, Egor; Dubinin, Eduard

    2017-04-01

    Solar wind induced atmospheric losses have been studied since earlier 1970th. Several loss channels have been identified including pick-up of exospheric photo-ions and ionospheric ions escape. Measurements performed during several solar cycles showed variation of these losses by about factor of 10, being largest at maximum solar activity. MAVEN spacecraft equipped with comprehensive set of instruments with high temporal and mass resolution operating at Mars since fall 2014 ensures much better investigation of solar wind enforcing Martian environment, Mars atmospheric losses processes and mass loss rate. These issues are very important for understanding of Martian atmospheric evolution including water loss during cosmogonic time. Simultaneous observations by MAVEN and MEX spacecraft open the new perspective in study of Martian environment. In this report we discuss results of past and current missions and preliminary analysis of heavy ions escape using simultaneous measurements of MEX and MAVEN spacecraft.

  9. Zika virus infection in Vietnam: current epidemic, strain origin, spreading risk, and perspective.

    Science.gov (United States)

    Chu, Dinh-Toi; Ngoc, Vo Truong Nhu; Tao, Yang

    2017-11-01

    Zika virus infection and its associated microcephaly have being receiving global concern. This infection has spread widely since the first outbreak was recorded in Africa in 1952. Now, it has been reported in over 70 countries on five continents including Africa, North and South America, Asia, and Europe. Vietnam is one of the most recent countries which had cases of Zika virus infection at the end of 2016. This country has also reported the first case of a microcephaly-born baby which was probably linked to Zika virus infection. However, information on the Zika virus epidemic in Vietnam is still limited. This brief report intends to update the current Zika virus epidemic, and to discuss challenges and perspectives in controlling this infection in Vietnam.

  10. Heparanase activates the syndecan-syntenin-ALIX exosome pathway

    National Research Council Canada - National Science Library

    Bart Roucourt Sofie Meeussen Jie Bao Pascale Zimmermann Guido David

    2015-01-01

    ... for transport accessory component ALIX. Here we investigated the role of heparanase, the only mammalian enzyme able to cleave heparan sulfate internally, in the syndecan-synten- in-ALIX exosome biogenesis pathway...

  11. Functional delivery of viral miRNAs via exosomes

    National Research Council Canada - National Science Library

    D. Michiel Pegtel; Katherine Cosmopoulos; David A. Thorley-Lawson; Monique A. J. van Eijndhoven; Erik S. Hopmans; Jelle L. Lindenberg; Tanja D. de Gruijl; Thomas Würdinger; Jaap M. Middeldorp; Elliott Kieff

    2010-01-01

    .... Interestingly, miRNAs are secreted actively through small vesicles called "exosomes" that protect them from degradation by RNases, suggesting that these miRNAs may function outside the cell in which they were produced...

  12. Current status of robotic training in the UK – a trainees perspective

    Directory of Open Access Journals (Sweden)

    Kaite E Chan

    2014-02-01

    Full Text Available The validation of robotic surgery in a growing number of operative procedures has increased its acceptance nationwide and its usage is becoming widespread. Training needs to reflect this fast paced environment to ensure that surgeons continue to progress competently and safely. Current surgical training in the UK is validated through the Intercollegiate Surgical Curriculum Programme (ISCP with progression assessed through an Annual Review of Curriculum Progress (ARCP. There has been some resistance to this since its introduction and many trainees remain dissatisfied with this programme. Training in robotic surgery is currently focused through fellowships with little regular exposure to urology trainees at more junior levels. Robotic simulation provides a useful adjunct to training for both technical and non-technical skills. Its usage is particularly valuable to more inexperienced trainees but may be of limited benefit in those with more advanced skills. Training programmes such as the fundamental skills in robotic surgery (FSRS have been created to facilitate robotic training and it is likely that the future of robotic surgery training will include a combination of theoretical learning, training programmes and fellowship training.-------------------------------------------------------Cite this article as: Chan KE, Vasdev N. Current status of robotic training in the UK – a trainees perspective. Int J Cancer Ther Oncol 2014; 2(1:02013.DOI: http://dx.doi.org/10.14319/ijcto.0201.3

  13. Nanoscale bio-platforms for living cell interrogation: current status and future perspectives

    Science.gov (United States)

    Chang, Lingqian; Hu, Jiaming; Chen, Feng; Chen, Zhou; Shi, Junfeng; Yang, Zhaogang; Li, Yiwen; Lee, Ly James

    2016-02-01

    The living cell is a complex entity that dynamically responds to both intracellular and extracellular environments. Extensive efforts have been devoted to the understanding intracellular functions orchestrated with mRNAs and proteins in investigation of the fate of a single-cell, including proliferation, apoptosis, motility, differentiation and mutations. The rapid development of modern cellular analysis techniques (e.g. PCR, western blotting, immunochemistry, etc.) offers new opportunities in quantitative analysis of RNA/protein expression up to a single cell level. The recent entries of nanoscale platforms that include kinds of methodologies with high spatial and temporal resolution have been widely employed to probe the living cells. In this tutorial review paper, we give insight into background introduction and technical innovation of currently reported nanoscale platforms for living cell interrogation. These highlighted technologies are documented in details within four categories, including nano-biosensors for label-free detection of living cells, nanodevices for living cell probing by intracellular marker delivery, high-throughput platforms towards clinical current, and the progress of microscopic imaging platforms for cell/tissue tracking in vitro and in vivo. Perspectives for system improvement were also discussed to solve the limitations remains in current techniques, for the purpose of clinical use in future.

  14. Effects of storage temperature on airway exosome integrity for diagnostic and functional analyses.

    Science.gov (United States)

    Maroto, Rosario; Zhao, Yingxin; Jamaluddin, Mohammad; Popov, Vsevolod L; Wang, Hongwang; Kalubowilage, Madumali; Zhang, Yueqing; Luisi, Jonathan; Sun, Hong; Culbertson, Christopher T; Bossmann, Stefan H; Motamedi, Massoud; Brasier, Allan R

    2017-01-01

    Background: Extracellular vesicles contain biological molecules specified by cell-type of origin and modified by microenvironmental changes. To conduct reproducible studies on exosome content and function, storage conditions need to have minimal impact on airway exosome integrity. Aim: We compared surface properties and protein content of airway exosomes that had been freshly isolated vs. those that had been treated with cold storage or freezing. Methods: Mouse bronchoalveolar lavage fluid (BALF) exosomes purified by differential ultracentrifugation were analysed immediately or stored at +4°C or -80°C. Exosomal structure was assessed by dynamic light scattering (DLS), transmission electron microscopy (TEM) and charge density (zeta potential, ζ). Exosomal protein content, including leaking/dissociating proteins, were identified by label-free LC-MS/MS. Results: Freshly isolated BALF exosomes exhibited a mean diameter of 95 nm and characteristic morphology. Storage had significant impact on BALF exosome size and content. Compared to fresh, exosomes stored at +4°C had a 10% increase in diameter, redistribution to polydisperse aggregates and reduced ζ. Storage at -80°C produced an even greater effect, resulting in a 25% increase in diameter, significantly reducing the ζ, resulting in multilamellar structure formation. In fresh exosomes, we identified 1140 high-confidence proteins enriched in 19 genome ontology biological processes. After storage at room temperature, 848 proteins were identified. In preparations stored at +4°C, 224 proteins appeared in the supernatant fraction compared to the wash fractions from freshly prepared exosomes; these proteins represent exosome leakage or dissociation of loosely bound "peri-exosomal" proteins. In preparations stored at -80°C, 194 proteins appeared in the supernatant fraction, suggesting that distinct protein groups leak from exosomes at different storage temperatures. Conclusions: Storage destabilizes the surface

  15. Exosomes derived from endometriotic stromal cells have enhanced angiogenic effects in vitro.

    Science.gov (United States)

    Harp, Djana; Driss, Adel; Mehrabi, Sharifeh; Chowdhury, Indrajit; Xu, Wei; Liu, Dong; Garcia-Barrio, Minerva; Taylor, Robert N; Gold, Bert; Jefferson, Samantha; Sidell, Neil; Thompson, Winston

    2016-07-01

    Our objective has been to establish a pro-angiogenic role for exosomes in endometriosis and to determine whether a differential expression profile of cellular and exosomal microRNAs (miRNAs) exists in endometriosis. We performed an in vitro study of human primary endometrial stromal cells (ESCs) and human umbilical vein endothelial cells (HUVECs). We isolated and characterized exosomes from ESCs from five endometriosis patients and five phase-matched controls. Exosomes were characterized by transmission electron microscopy and NanoSight technology. MiRNA was assessed by deep sequencing and reverse transcription with quantitative polymerase chain reaction. Exosome uptake studies were achieved by means of confocal microscopy. The pro-angiogenic experiments were executed by treating HUVECs with ESC-derived exosomes. We observed differential profiles of exosomal miRNA expression between exosomes derived from endometriosis lesion cells and diseased eutopic stromal cells compared with exosomes derived from control ESCs. We also demonstrated autocrine cellular uptake of exosomes and paracrine functional angiogenic effects of exosomes on HUVECs. The results of this study support the hypothesis that exosomes derived from ESCs play autocrine/paracrine roles in the development of endometriosis, potentially modulating angiogenesis. The broader clinical implications are that Sampson's theory of retrograde menstruation possibly encompasses the finding that exosomes work as intercellular communication modulators in endometriosis.

  16. Tumor-derived exosomes in cancer progression and treatment failure

    Science.gov (United States)

    Shen, Bo; Feng, Jifeng

    2015-01-01

    Exosomes have diameter within the range of 30-100nm and spherical to cup-shaped nanoparticles with specific surface molecular characteristics, such as CD9 and CD63. These vesicles are present in nearly all human body fluids, including blood plasma/serum, saliva, breast milk, cerebrospinal fluid, urine, semen, and particularly enriched in tumor microenvironment. Exosomes contain multiple proteins, DNA, mRNA, miRNA, long non-coding RNA, and even genetic materials of viruses/prions. These materials are biochemically and functionally distinct and can be transferred to a recipient cell where they regulate protein expression and signaling pathways. Recently, exosomes are demonstrated to have a close relationship with tumor development and metastasis. Exosomes influence therapeutic effect in cancer patients. In this review, we describe the biogenesis, composition, and function of exosomes. The mechanism on how tumor-derived exosomes contribute to cancer progression and clinical treatment failure is also described, with special focus on their potential applications in cancer therapy. PMID:26452221

  17. Small RNA Library Construction for Exosomal RNA from Biological Samples for the Ion Torrent PGM™ and Ion S5™ System.

    Science.gov (United States)

    Cheng, Lesley; Hill, Andrew F

    2017-01-01

    Next-generation deep sequencing (NGS) technology represents a powerful and innovative approach to profile small RNA. Currently, there are a number of large-scale and benchtop sequencing platforms available on the market. Although each platform is relatively straightforward to operate, constructing cDNA libraries can be the most difficult part of the NGS workflow. Constructing quality libraries is essential to obtaining a successful sequencing run of high-quality reads and coverage. The quality and yield of RNA affect hybridization and ligation of sequencing adapters. In the field of biomarker discovery, there has been an interest in profiling exosomal RNA from biological fluids. However, very little RNA yield is obtained when extracting RNA from exosomes, thus making library construction difficult. Here, this protocol describes an optimized protocol for constructing small RNA libraries from low yields of RNA, in particular, extracted from exosomes isolated from biological fluids.

  18. Cells release subpopulations of exosomes with distinct molecular and biological properties.

    Science.gov (United States)

    Willms, Eduard; Johansson, Henrik J; Mäger, Imre; Lee, Yi; Blomberg, K Emelie M; Sadik, Mariam; Alaarg, Amr; Smith, C I Edvard; Lehtiö, Janne; El Andaloussi, Samir; Wood, Matthew J A; Vader, Pieter

    2016-03-02

    Cells release nano-sized membrane vesicles that are involved in intercellular communication by transferring biological information between cells. It is generally accepted that cells release at least three types of extracellular vesicles (EVs): apoptotic bodies, microvesicles and exosomes. While a wide range of putative biological functions have been attributed to exosomes, they are assumed to represent a homogenous population of EVs. We hypothesized the existence of subpopulations of exosomes with defined molecular compositions and biological properties. Density gradient centrifugation of isolated exosomes revealed the presence of two distinct subpopulations, differing in biophysical properties and their proteomic and RNA repertoires. Interestingly, the subpopulations mediated differential effects on the gene expression programmes in recipient cells. In conclusion, we demonstrate that cells release distinct exosome subpopulations with unique compositions that elicit differential effects on recipient cells. Further dissection of exosome heterogeneity will advance our understanding of exosomal biology in health and disease and accelerate the development of exosome-based diagnostics and therapeutics.

  19. A European Perspective on Auditory Processing Disorder-Current Knowledge and Future Research Focus

    Science.gov (United States)

    Iliadou, Vasiliki (Vivian); Ptok, Martin; Grech, Helen; Pedersen, Ellen Raben; Brechmann, André; Deggouj, Naïma; Kiese-Himmel, Christiane; Śliwińska-Kowalska, Mariola; Nickisch, Andreas; Demanez, Laurent; Veuillet, Evelyne; Thai-Van, Hung; Sirimanna, Tony; Callimachou, Marina; Santarelli, Rosamaria; Kuske, Sandra; Barajas, Jose; Hedjever, Mladen; Konukseven, Ozlem; Veraguth, Dorothy; Stokkereit Mattsson, Tone; Martins, Jorge Humberto; Bamiou, Doris-Eva

    2017-01-01

    Current notions of “hearing impairment,” as reflected in clinical audiological practice, do not acknowledge the needs of individuals who have normal hearing pure tone sensitivity but who experience auditory processing difficulties in everyday life that are indexed by reduced performance in other more sophisticated audiometric tests such as speech audiometry in noise or complex non-speech sound perception. This disorder, defined as “Auditory Processing Disorder” (APD) or “Central Auditory Processing Disorder” is classified in the current tenth version of the International Classification of diseases as H93.25 and in the forthcoming beta eleventh version. APDs may have detrimental effects on the affected individual, with low esteem, anxiety, and depression, and symptoms may remain into adulthood. These disorders may interfere with learning per se and with communication, social, emotional, and academic-work aspects of life. The objective of the present paper is to define a baseline European APD consensus formulated by experienced clinicians and researchers in this specific field of human auditory science. A secondary aim is to identify issues that future research needs to address in order to further clarify the nature of APD and thus assist in optimum diagnosis and evidence-based management. This European consensus presents the main symptoms, conditions, and specific medical history elements that should lead to auditory processing evaluation. Consensus on definition of the disorder, optimum diagnostic pathway, and appropriate management are highlighted alongside a perspective on future research focus.

  20. Current perspectives for management of acute respiratory insufficiency in premature infants with acute respiratory syndrome.

    Science.gov (United States)

    Chen, Peng; Zhang, Ying; Li, Long-Yun

    2014-09-01

    Current perspectives for management of acute respiratory insufficiency in premature infants with acute respiratory syndrome and the pathology of acute respiratory insufficiency in the preterm infant, including the current therapy modalities on disposition are presented. Since the therapeutical challenge and primary clinical goal are to normalize ventilation ratio and lung perfusion, when respiratory insufficiency occurs, it is very important to introduce the respiratory support as soon possible, in order to reduce development of pulmonary cyanosis and edema, and intrapulmonary or intracardial shunts. A characteristic respiratory instability that reflects through fluctuations in gas exchange and ventilation is often present in premature infants. Adapting the respiratory support on a continuous basis to the infant's needs is challenging and not always effective. Although a large number of ventilation strategies for the neonate are available, there is a need for additional consensus on management of acute respiratory distress syndrome in pediatric population lately redefined by Berlin definition criteria, in order to efficiently apply various modes of respiratory support in daily pediatrician clinical use.

  1. A European Perspective on Auditory Processing Disorder-Current Knowledge and Future Research Focus

    Directory of Open Access Journals (Sweden)

    Vasiliki (Vivian Iliadou

    2017-11-01

    Full Text Available Current notions of “hearing impairment,” as reflected in clinical audiological practice, do not acknowledge the needs of individuals who have normal hearing pure tone sensitivity but who experience auditory processing difficulties in everyday life that are indexed by reduced performance in other more sophisticated audiometric tests such as speech audiometry in noise or complex non-speech sound perception. This disorder, defined as “Auditory Processing Disorder” (APD or “Central Auditory Processing Disorder” is classified in the current tenth version of the International Classification of diseases as H93.25 and in the forthcoming beta eleventh version. APDs may have detrimental effects on the affected individual, with low esteem, anxiety, and depression, and symptoms may remain into adulthood. These disorders may interfere with learning per se and with communication, social, emotional, and academic-work aspects of life. The objective of the present paper is to define a baseline European APD consensus formulated by experienced clinicians and researchers in this specific field of human auditory science. A secondary aim is to identify issues that future research needs to address in order to further clarify the nature of APD and thus assist in optimum diagnosis and evidence-based management. This European consensus presents the main symptoms, conditions, and specific medical history elements that should lead to auditory processing evaluation. Consensus on definition of the disorder, optimum diagnostic pathway, and appropriate management are highlighted alongside a perspective on future research focus.

  2. Brain-Computer Interfaces Using Sensorimotor Rhythms: Current State and Future Perspectives

    Science.gov (United States)

    Yuan, Han; He, Bin

    2014-01-01

    Many studies over the past two decades have shown that people can use brain signals to convey their intent to a computer using brain-computer interfaces (BCIs). BCI systems extract specific features of brain activity and translate them into control signals that drive an output. Recently, a category of BCIs that are built on the rhythmic activity recorded over the sensorimotor cortex, i.e. the sensorimotor rhythm (SMR), has attracted considerable attention among the BCIs that use noninvasive neural recordings, e.g. electroencephalography (EEG), and have demonstrated the capability of multi-dimensional prosthesis control. This article reviews the current state and future perspectives of SMR-based BCI and its clinical applications, in particular focusing on the EEG SMR. The characteristic features of SMR from the human brain are described and their underlying neural sources are discussed. The functional components of SMR-based BCI, together with its current clinical applications are reviewed. Lastly, limitations of SMR-BCIs and future outlooks are also discussed. PMID:24759276

  3. BIOBANKS ARE AN ESSENTIAL TOOL FOR TRANSPLANTATION. HISTORY, CURRENT STATE, PERSPECTIVES

    Directory of Open Access Journals (Sweden)

    O. N. Reznik

    2016-01-01

    Full Text Available Organ shortage remains to be a crucial issue in transplantation. However, it’s not the only challenge that modern transplantation is facing. There are critical issues to be solved, such as, choosing optimal patient-specific immunosuppressive regimen, preventing or coping effectively with graft rejection and improving graft and patient survival rates. There are still a number of ongoing studies on ischemia-reperfusion injury mechanisms. It is also unknown what the true limitations of organ viability are and what mechanisms actually regulate it. The upcoming era of personalized medicine dictates the necessity for individualized approach to these issues. The creation of transplant biobanks followed by different studies on their base may be the key option to resolve problems of modern transplantation. Biobanks are an essential basis of personalized medicine, which allows largescale population studies, discovery of new biomarkers and therapy targets as well as new drugs development. The importance of this relatively new fi eld has increased over last decades making its way from small collections of samples to large national and international biorepositories. There are biobanks of different types and purposes. In this article a systematic review is given covering historical reference, term definition, and classifi cation variants. Furthermore, the current state of the industry is highlighted along with current issues and perspectives with respect to transplantation.

  4. Current perspectives on biomedical waste management: Rules, conventions and treatment technologies

    Directory of Open Access Journals (Sweden)

    Malini R Capoor

    2017-01-01

    Full Text Available Unregulated biomedical waste management (BMWM is a public health problem. This has posed a grave threat to not only human health and safety but also to the environment for the current and future generations. Safe and reliable methods for handling of biomedical waste (BMW are of paramount importance. Effective BMWM is not only a legal necessity but also a social responsibility. This article reviews the current perspectives on BMWM and rules, conventions and the treatment technologies used worldwide. BMWM should ideally be the subject of a national strategy with dedicated infrastructure, cradle-to-grave legislation, competent regulatory authority and trained personnel. Improving the management of biomedical waste begins with waste minimisation. These standards, norms and rules on BMWM in a country regulate the disposal of various categories of BMW to ensure the safety of the health-care workers, patients, public and environment. Furthermore, developing models for the monitoring of hospital health-care waste practices and research into non-burn eco-friendly sustainable technologies, recycling and polyvinyl chloride-free devices will go in long way for safe carbon environment. Globally, greater research in BMWM is warranted to understand its growing field of public health importance.

  5. Exosome Cofactors Connect Transcription Termination to RNA Processing by Guiding Terminated Transcripts to the Appropriate Exonuclease within the Nuclear Exosome.

    Science.gov (United States)

    Kim, Kyumin; Heo, Dong-Hyuk; Kim, Iktae; Suh, Jeong-Yong; Kim, Minkyu

    2016-06-17

    The yeast Nrd1 interacts with the C-terminal domain (CTD) of RNA polymerase II (RNApII) through its CTD-interacting domain (CID) and also associates with the nuclear exosome, thereby acting as both a transcription termination and RNA processing factor. Previously, we found that the Nrd1 CID is required to recruit the nuclear exosome to the Nrd1 complex, but it was not clear which exosome subunits were contacted. Here, we show that two nuclear exosome cofactors, Mpp6 and Trf4, directly and competitively interact with the Nrd1 CID and differentially regulate the association of Nrd1 with two catalytic subunits of the exosome. Importantly, Mpp6 promotes the processing of Nrd1-terminated transcripts preferentially by Dis3, whereas Trf4 leads to Rrp6-dependent processing. This suggests that Mpp6 and Trf4 may play a role in choosing a particular RNA processing route for Nrd1-terminated transcripts within the exosome by guiding the transcripts to the appropriate exonuclease. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. EXOSOMES: CAN DOCTORS STILL IGNORE THEIR EXISTENCE?

    Directory of Open Access Journals (Sweden)

    Celeste Caruso Bavisotto

    2013-04-01

    Full Text Available With this invited commentary we want to draw the attention of young medical doctors, the main readers of this journal, towards the existence and importance of a group of nanovesicles released by human cells: the exosomes. These vesicles are incontinently secreted as a mean of cell-to-cell communication. They are involved in a number of physiologic processes as well as in the pathogenesis of, virtually, all human diseases. They can be isolated from all biological fluids, like blood, urine, sweat, sperm, crevicular fluid, bile, etc., and their composition in terms of proteins, RNA and lipids is different in pathology that in physiologic conditions. It is therefore possible to predict that they will become an important diagnostic and therapeutic tool in medicine.

  7. Exosomes Derived from Squamous Head and Neck Cancer Promote Cell Survival after Ionizing Radiation

    Science.gov (United States)

    Mutschelknaus, Lisa; Peters, Carsten; Winkler, Klaudia; Yentrapalli, Ramesh; Heider, Theresa; Atkinson, Michael John; Moertl, Simone

    2016-01-01

    Exosomes are nanometer-sized extracellular vesicles that are believed to function as intercellular communicators. Here, we report that exosomes are able to modify the radiation response of the head and neck cancer cell lines BHY and FaDu. Exosomes were isolated from the conditioned medium of irradiated as well as non-irradiated head and neck cancer cells by serial centrifugation. Quantification using NanoSight technology indicated an increased exosome release from irradiated compared to non-irradiated cells 24 hours after treatment. To test whether the released exosomes influence the radiation response of other cells the exosomes were transferred to non-irradiated and irradiated recipient cells. We found an enhanced uptake of exosomes isolated from both irradiated and non-irradiated cells by irradiated recipient cells compared to non-irradiated recipient cells. Functional analyses by exosome transfer indicated that all exosomes (from non-irradiated and irradiated donor cells) increase the proliferation of non-irradiated recipient cells and the survival of irradiated recipient cells. The survival-promoting effects are more pronounced when exosomes isolated from irradiated compared to non-irradiated donor cells are transferred. A possible mechanism for the increased survival after irradiation could be the increase in DNA double-strand break repair monitored at 6, 8 and 10 h after the transfer of exosomes isolated from irradiated cells. This is abrogated by the destabilization of the exosomes. Our results demonstrate that radiation influences both the abundance and action of exosomes on recipient cells. Exosomes transmit prosurvival effects by promoting the proliferation and radioresistance of head and neck cancer cells. Taken together, this study indicates a functional role of exosomes in the response of tumor cells to radiation exposure within a therapeutic dose range and encourages that exosomes are useful objects of study for a better understanding of tumor

  8. Exosomes as potent regulators of HCC malignancy and potential bio-tools in clinical application

    OpenAIRE

    Qu, Zhen; Jiang, Chunping; Wu, Junhua; Ding, Yitao

    2015-01-01

    Exosomes are small membranous vesicles about 30~100 nm in diameter and formed from inward budding of the limiting membrane of multi-vesicular bodies (MVB). Exosomes are secreted by most cell types (including hepatocellular carcinoma cells) into the extracellular environment and can be isolated from various body fluids. Exosomes have broad biological function through delivering contained molecules to the target cells. Although limited studies on hepatocellular carcinoma (HCC) exosomes, increas...

  9. Isolation and characterization of exosomes from cell culture supernatants and biological fluids

    OpenAIRE

    Théry, Clotilde; Amigorena, Sebastian; Raposo, Graça; Clayton, Aled

    2006-01-01

    Exosomes are small membrane vesicles found in cell culture supernatants and in different biological fluids. Exosomes form in a particular population of endosomes, called multivesicular bodies (MVBs), by inward budding into the lumen of the compartment. Upon fusion of MVBs with the plasma membrane, these internal vesicles are secreted. Exosomes possess a defined set of membrane and cytosolic proteins. The physiological function of exosomes is still a matter of debate, but increasing results in...

  10. Demographic and traditional knowledge perspectives on the current status of Canadian polar bear subpopulations.

    Science.gov (United States)

    York, Jordan; Dowsley, Martha; Cornwell, Adam; Kuc, Miroslaw; Taylor, Mitchell

    2016-05-01

    Subpopulation growth rates and the probability of decline at current harvest levels were determined for 13 subpopulations of polar bears (Ursus maritimus) that are within or shared with Canada based on mark-recapture estimates of population numbers and vital rates, and harvest statistics using population viability analyses (PVA). Aboriginal traditional ecological knowledge (TEK) on subpopulation trend agreed with the seven stable/increasing results and one of the declining results, but disagreed with PVA status of five other declining subpopulations. The decline in the Baffin Bay subpopulation appeared to be due to over-reporting of harvested numbers from outside Canada. The remaining four disputed subpopulations (Southern Beaufort Sea, Northern Beaufort Sea, Southern Hudson Bay, and Western Hudson Bay) were all incompletely mark-recapture (M-R) sampled, which may have biased their survival and subpopulation estimates. Three of the four incompletely sampled subpopulations were PVA identified as nonviable (i.e., declining even with zero harvest mortality). TEK disagreement was nonrandom with respect to M-R sampling protocols. Cluster analysis also grouped subpopulations with ambiguous demographic and harvest rate estimates separately from those with apparently reliable demographic estimates based on PVA probability of decline and unharvested subpopulation growth rate criteria. We suggest that the correspondence between TEK and scientific results can be used to improve the reliability of information on natural systems and thus improve resource management. Considering both TEK and scientific information, we suggest that the current status of Canadian polar bear subpopulations in 2013 was 12 stable/increasing and one declining (Kane Basin). We do not find support for the perspective that polar bears within or shared with Canada are currently in any sort of climate crisis. We suggest that monitoring the impacts of climate change (including sea ice decline) on polar bear

  11. A survey on IVIVC/IVIVR development in the pharmaceutical industry - Past experience and current perspectives.

    Science.gov (United States)

    Nguyen, M A; Flanagan, T; Brewster, M; Kesisoglou, F; Beato, S; Biewenga, J; Crison, J; Holm, R; Li, R; Mannaert, E; McAllister, M; Mueller-Zsigmondy, M; Muenster, U; Ojala, K; Page, S; Parr, A; Rossenu, S; Timmins, P; Van Peer, A; Vermeulen, A; Langguth, P

    2017-05-01

    The present work aimed to describe the current status of IVIVC/IVIVR development in the pharmaceutical industry, focusing on the use and perception of specific approaches as well as successful and failed case studies. Two questionnaires have been distributed to 13 EFPIA partners of the Oral Biopharmaceutics Tools Initiative and to the Pharmacokinetics Working Party of the European Medicines Agency in order to capture the perspectives and experiences of industry scientists and agency members, respectively. Responses from ten companies and three European Agencies were received between May 21st 2014 and January 19th 2016. The majority of the companies acknowledged the importance of IVIVC/IVIVR throughout the drug development stages and a well-balanced rate of return on investment. However, the IVIVC/IVIVR approach seemed to be underutilized in regulatory submissions. Four of the ten companies stated to have an internal guidance related to IVIVC/IVIVR modelling, whereas three felt that an overall strategy is not necessary. Successful models mainly served to support formulation development and to provide a better mechanistic understanding. There was not yet much experience with safe-space IVIVRs as well as the use of physiologically based modelling in the field of IVIVC. At the same time, the responses from both industry and agencies indicated that there might be a need for a regulatory framework to guide the application of these novel approaches. The relevance of IVIVC/IVIVR for oral IR drug products was recognized by most of the companies. For IR formulations, relationships other than Level A correlation were more common outcomes among the provided case studies, such as multiple Level C correlation or safe-space IVIVR, which could be successfully used for requesting regulatory flexibility. Compared to the responses from industry scientists, there was a trend towards a higher appreciation of the BCS among the regulators, but a less positive attitude towards the utility

  12. Release of luminal exosomes contributes to TLR4-mediated epithelial antimicrobial defense.

    Directory of Open Access Journals (Sweden)

    Guoku Hu

    Full Text Available Exosomes are membranous nanovesicles released by most cell types from multi-vesicular endosomes. They are speculated to transfer molecules to neighboring or distant cells and modulate many physiological and pathological procedures. Exosomes released from the gastrointestinal epithelium to the basolateral side have been implicated in antigen presentation. Here, we report that luminal release of exosomes from the biliary and intestinal epithelium is increased following infection by the protozoan parasite Cryptosporidium parvum. Release of exosomes involves activation of TLR4/IKK2 signaling through promoting the SNAP23-associated vesicular exocytotic process. Downregulation of let-7 family miRNAs by activation of TLR4 signaling increases SNAP23 expression, coordinating exosome release in response to C. parvum infection. Intriguingly, exosomes carry antimicrobial peptides of epithelial cell origin, including cathelicidin-37 and beta-defensin 2. Activation of TLR4 signaling enhances exosomal shuttle of epithelial antimicrobial peptides. Exposure of C. parvum sporozoites to released exosomes decreases their viability and infectivity both in vitro and ex vivo. Direct binding to the C. parvum sporozoite surface is required for the anti-C. parvum activity of released exosomes. Biliary epithelial cells also increase exosomal release and display exosome-associated anti-C. parvum activity following LPS stimulation. Our data indicate that TLR4 signaling regulates luminal exosome release and shuttling of antimicrobial peptides from the gastrointestinal epithelium, revealing a new arm of mucosal immunity relevant to antimicrobial defense.

  13. Purified horse milk exosomes contain an unpredictable small number of major proteins

    Directory of Open Access Journals (Sweden)

    Sergey E. Sedykh

    2017-06-01

    The article describes the morphology and the protein content of major horse milk exosomes for the first time. Our results on the decrease of major protein number identified in exosomal preparations after gel filtration may be important to the studies of biological functions of pure exosomes.

  14. Inflammasome-Derived Exosomes Activate NF-κB Signaling in Macrophages.

    Science.gov (United States)

    Zhang, Yuehui; Liu, Fangbing; Yuan, Yanzhi; Jin, Chaozhi; Chang, Cheng; Zhu, Yunping; Zhang, Xiuyuan; Tian, Chunyan; He, Fuchu; Wang, Jian

    2017-01-06

    Exosomes are secreted small vesicles that mediate various biological processes, such as tumorigenesis and immune response. However, whether the inflammasome signaling leads to the change of constituent of exosomes and its roles in immune response remains to be determined. We isolated the exosomes from macrophages with treatment of mock, endotoxin, or endotoxin/nigericin. A label-free quantification method by MS/MS was used to identify the components of exosomes. In total, 2331 proteins were identified and 513 proteins were exclusively detected in exosomes with endotoxin and nigericin treatment. The differentially expressed proteins were classified by Gene Ontology and KEGG pathways. The immune response-related proteins and signaling pathways were specifically enriched in inflammasome-derived exosomes. Moreover, we treated macrophages with the exosomes from different stimulation. We found that inflammasome-derived exosomes directly activate NF-κB signaling pathway, while the control or endotoxin-derived exosomes have no effect. The inflammatory signaling was amplified in neighbor cells in an exosome-dependent way. The inflammasome-derived exosomes might be used to augment the immune response in disease treatment, and preventing the transfer of these exosomes might ameliorate autoimmune diseases.

  15. BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression

    National Research Council Canada - National Science Library

    Roccaro, Aldo M; Sacco, Antonio; Maiso, Patricia; Azab, Abdel Kareem; Tai, Yu-Tzu; Reagan, Michaela; Azab, Feda; Flores, Ludmila M; Campigotto, Federico; Weller, Edie; Anderson, Kenneth C; Scadden, David T; Ghobrial, Irene M

    2013-01-01

    .... Cell-cell communication is mediated by exosomes. In this study, we showed that MM BM-MSCs release exosomes that are transferred to MM cells, thereby resulting in modulation of tumor growth in vivo. Exosomal microRNA (miR...

  16. Announcing , the Official Journal of the American Society for Exosomes and Microvesicles

    Directory of Open Access Journals (Sweden)

    Stephen J. Gould

    2013-01-01

    Full Text Available This editorial article introduces the new scientific journal Exosomes and Microvesicles (EXMV , the official journal of the American Society for Exosomes and Microvesicles (ASEMV, and describes its editorial line and mission in relation to the role of the Society, the state of the art of the study of exosomes and microvesicles, and the overall approach of the publication.

  17. Exosomes as Mediators of the Systemic Adaptations to Endurance Exercise.

    Science.gov (United States)

    Safdar, Adeel; Tarnopolsky, Mark A

    2017-05-10

    Habitual endurance exercise training is associated with multisystemic metabolic adaptations that lower the risk of inactivity-associated disorders such as obesity and type 2 diabetes mellitus (T2DM). Identification of complex systemic signaling networks responsible for these benefits are of great interest because of their therapeutic potential in metabolic diseases; however, specific signals that modulate the multisystemic benefits of exercise in multiple tissues and organs are only recently being discovered. Accumulated evidence suggests that muscle and other tissues have an endocrine function and release peptides and nucleic acids into the circulation in response to acute endurance exercise to mediate the multisystemic adaptations. Factors released from skeletal muscle have been termed myokines and we propose that the total of all factors released in response to endurance exercise (including peptides, nucleic acids, and metabolites) be termed, "exerkines." We propose that many of the exerkines are released within extracellular vesicles called exosomes, which regulate peripheral organ cross talk. Exosomes (30-140 nm) and larger microvesicles [MVs] (100-1000 nm) are subcategories of extracellular vesicles that are released into the circulation. Exosomes contain peptides and several nucleic acids (microRNA [miRNA], messenger RNA [mRNA], mitochondrial DNA [mtDNA]) and are involved in intercellular/tissue exchange of their contents. An acute bout of endurance exercise increases circulating exosomes that are hypothesized to mediate organ cross talk to promote systemic adaptation to endurance exercise. Further support for the role of exosomes (and possibly MVs) in mediating the systemic benefits of exercise comes from the fact that the majority of the previously reported myokines/exerkines are found in extracellular vesicles databases (Vesiclepedia and ExoCarta). We propose that exosomes isolated from athletes following exercise or exosomes bioengineered to incorporate

  18. Tumour exosomes from cells harbouring PTPRZ1-MET fusion contribute to a malignant phenotype and temozolomide chemoresistance in glioblastoma.

    Science.gov (United States)

    Zeng, A-L; Yan, W; Liu, Y-W; Wang, Z; Hu, Q; Nie, E; Zhou, X; Li, R; Wang, X-F; Jiang, T; You, Y-P

    2017-09-21

    Exosomes are carriers of pro-tumorigenic factors that participate in glioblastoma (GBM) progression, and many fusion genes are strong driver mutations in neoplasia and are involved in tumorigenesis. However, the ability of fusion genes to be transduced by exosomes is unknown. We characterized exosomes from GBM cells harbouring and not harbouring PTPRZ1-MET fusion (ZM fusion). We also determined the effect of the exosomes from ZM fusion cells (ZM exosomes) on pro-oncogenic secretions and showed that ZM exosomes are internalized by the recipient cells. In addition, we studied the effect of ZM exosome-mediated intercellular communication in the GBM microenvironment. MET proto-oncogene expression was higher in ZM exosomes. Moreover, phosphorylated MET was detected only in ZM exosomes and not in exosomes released by non-ZM fusion GBM cells. ZM exosomes transferred to non-ZM fusion GBM cells and normal human astrocytes altered gene expression and induced epithelial-mesenchymal transition. The uptake of ZM exosomes also induced an exosome-dependent phenotype defined by GBM cell migration and invasion, neurosphere growth and angiogenesis. In addition, ZM exosomes conferred temozolomide resistance to the GBM cells, and exosome-derived ZM fusion network proteins targeted multiple pro-oncogenic effectors in recipient cells within the GBM microenvironment. Our findings show that exosomes mediate the aggressive character of GBM and demonstrate the role of ZM fusion in the exacerbation of this effect. These findings have possible implications for the foundation of gene fusion-based therapy for managing GBM.

  19. Current technologies, economics, and perspectives for 2,5-dimethylfuran production from biomass-derived intermediates.

    Science.gov (United States)

    Saha, Basudeb; Abu-Omar, Mahdi M

    2015-04-13

    Since the U.S. Department of Energy (DOE) published a perspective article that described the potential of the top ten biomass-derived platform chemicals as petroleum replacements for high-value commodity and specialty chemicals, researchers around the world have been motivated to develop technologies for the conversion of biomass and biomass-derived intermediates into chemicals and fuels. Among several biorefinery processes, the conversion of biomass carbohydrates into 2,5-dimethylfuran (DMF) has received significant attention because of its low oxygen content, high energy content, and high octane value. DMF can further serve as a petroleum-replacement, biorenewable feedstock for the production of p-xylene (pX). In this review, we aim specifically to present a concise and up-to-date analysis of DMF production technologies with a critical discussion on catalytic systems, mechanistic insight, and process economics, which includes sensitivity analysis, so that more effective catalysts can be designed. Special emphasis has been given to bifunctional catalysts that improve DMF yields and selectivity and the synergistic effect of the bifunctional sites. Process economics for the current processes and the scope for further improvement are discussed. It is anticipated that the chemistry detailed in this review will guide researchers to develop more practical catalytic processes to enable the economic production of bio-based DMF. Processes for the upgrade of DMF to pX are also described. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Corrosion Protection Systems and Fatigue Corrosion in Offshore Wind Structures: Current Status and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Seth J. Price

    2017-02-01

    Full Text Available Concerns over reducing CO2 emissions associated with the burning of fossil fuels in combination with an increase in worldwide energy demands is leading to increased development of renewable energies such as wind. The installation of offshore wind power structures (OWS is one of the most promising approaches for the production of renewable energy. However, corrosion and fatigue damage in marine and offshore environments are major causes of primary steel strength degradation in OWS. Corrosion can reduce the thickness of structural components which may lead towards fatigue crack initiation and buckling. These failure mechanisms affect tower service life and may result in catastrophic structural failure. Additionally, environmental pollution stemming from corrosion’s by-products is possible. As a result, large financial investments are made yearly for both the prevention and recovery of these drawbacks. The corrosion rate of an OWS is dependent on different characteristics of attack which are influenced by access to oxygen and humidity. Structural degradation can occur due to chemical attack, abrasive action of waves, and microorganism attacks. Inspired by technological and scientific advances in recent years, the purpose of this paper is to discuss the current protective coating system technologies used to protect OWS as well as future perspectives.

  1. Current gaps in understanding and predicting space weather: An operations perspective

    Science.gov (United States)

    Murtagh, W. J.

    2016-12-01

    The NOAA Space Weather Prediction Center (SWPC), one of the nine National Weather Service (NWS) National Centers for Environmental Prediction, is the Nation's official source for space weather alerts and warnings. Space weather effects the technology that forms the backbone of global economic vitality and national security, including satellite and airline operations, communications networks, and the electric power grid. Many of SWPC's over 48,000 subscribers rely on space weather forecasts for critical decision making. But extraordinary gaps still exist in our ability to meet customer needs for accurate and timely space weather forecasts and warnings. The 2015 National Space Weather Strategy recognizes that it is imperative that we improve the fundamental understanding of space weather and increase the accuracy, reliability, and timeliness of space-weather observations and forecasts in support of the growing demands. In this talk we provide a broad perspective of the key challenges that currently limit the forecaster's ability to better understand and predict space weather. We also examine the impact of these limitations on the end-user community.

  2. Opening the black box of Anaplasma phagocytophilum diversity: current situation and future perspectives

    Directory of Open Access Journals (Sweden)

    Thibaud eDugat

    2015-08-01

    Full Text Available Anaplasma phagocytophilum is a zoonotic obligate intracellular bacterium known to be transmitted by ticks belonging to the Ixodes persulcatus complex. This bacterium can infect several mammalian species, and is known to cause diseases with variable symptoms in many domestic animals. Specifically, it is the causative agent of tick-borne fever, a disease of important economic impact in European domestic ruminants, and human granulocytic anaplasmosis, an emerging zoonotic disease in both the USA and Europe. A. phagocytophilum epidemiological cycles are complex and involve different ecotypes, vectors, and mammalian host species. Moreover, the epidemiology of A. phagocytophilum infection differs greatly between Europe and the USA. These different epidemiological contexts are associated with considerable variations in bacterial strains. Until recently, few A. phagocytophilum molecular typing tools were available, generating difficulties in completely elucidating the epidemiological cycles of this bacterium. Over the last few years, many A. phagocytophilum typing techniques have been developed, permitting in-depth epidemiological exploration. Here, we review the current knowledge and future perspectives regarding A. phagocytophilum epidemiology and phylogeny, and then focus on the molecular typing tools available for studying A. phagocytophilum genetic diversity.

  3. The development of family nursing in Denmark: current status and future perspectives.

    Science.gov (United States)

    Østergaard, Birte; Wagner, Lis

    2014-11-01

    Over the past 12 years, a strong foundation for family nursing has been built in Denmark, with rapid growth in the past 3 years. A review of nursing research conducted in Denmark and published between 2002 and 2013 found 15 studies that examined family phenomena. The majority of the studies used descriptive methods with data collected from surveys and interviews involving family members either together or individually. Only five of the studies examined interventions that included families' perspectives about the intervention being evaluated. Several current research projects lead by Danish nurses examine the implementation of family nursing knowledge to clinical settings. Integration of family nursing theory has begun in Denmark in undergraduate and graduate nursing curricula and in May 2013, the Danish Family Nursing Association was officially established. Infrastructure and financial conference support has made it possible to invite Nordic and international colleagues to meet in Denmark, which, reciprocally, expands understanding and support for family nursing within the country. Further collaboration between Danish nurse researchers, educators, and administrators will help sustain the growth of family nursing science and its application in family-focused nursing practice. © The Author(s) 2014.

  4. Patient and citizen participation in German health care--current state and future perspectives.

    Science.gov (United States)

    Loh, Andreas; Simon, Daniela; Bieber, Christiane; Eich, Wolfgang; Härter, Martin

    2007-01-01

    Patient participation within the German healthcare system is described at three different levels: the macro level as active patient influence on the regulation of medical care, the meso level in terms of institutions enhancing patient information and counselling, and the micro level focusing on the actual treatment decision-making process in the medical encounter. The main focus of the present publication is on the health care system-specific influences on patient participation in medical decision-making and on the current state of research and implementation of shared decision-making in Germany. We describe institutions promoting patient involvement, their aims and initiatives as well as recent changes in German legislation. Against the background of German health politics' endorsement of patient participation the German Ministry of Health funded a research consortium with shared decision-making intervention projects in various disease areas. The present state of the intervention projects' results is outlined as well as subsequently funded transfer projects and future perspectives of research grants. Supported by health politics and the utilisation of scientific evidence shared decision-making's transfer into practice is considered to be relevant to the German health care system.

  5. Canine and feline vector-borne diseases in Italy: current situation and perspectives

    Directory of Open Access Journals (Sweden)

    Dantas-Torres Filipe

    2010-01-01

    Full Text Available Abstract In Italy, dogs and cats are at risk of becoming infected by different vector-borne pathogens, including protozoa, bacteria, and helminths. Ticks, fleas, phlebotomine sand flies, and mosquitoes are recognized vectors of pathogens affecting cats and dogs, some of which (e.g., Anaplasma phagocytophilum, Borrelia burgdorferi, Dipylidium caninum, Leishmania infantum, Dirofilaria immitis, and Dirofilaria repens are of zoonotic concern. Recent studies have highlighted the potential of fleas as vectors of pathogens of zoonotic relevance (e.g., Rickettsia felis in this country. While some arthropod vectors (e.g., ticks and fleas are present in certain Italian regions throughout the year, others (e.g., phlebotomine sand flies are most active during the summer season. Accordingly, control strategies, such as those relying on the systematic use of acaricides and insecticides, should be planned on the basis of the ecology of both vectors and pathogens in different geographical areas in order to improve their effectiveness in reducing the risk of infection by vector-borne pathogens. This article reviews the current situation and perspectives of canine and feline vector-borne diseases in Italy.

  6. Current and Future Perspectives on the Structural Identification of Small Molecules in Biological Systems

    Directory of Open Access Journals (Sweden)

    Daniel A. Dias

    2016-12-01

    Full Text Available Although significant advances have been made in recent years, the structural elucidation of small molecules continues to remain a challenging issue for metabolite profiling. Many metabolomic studies feature unknown compounds; sometimes even in the list of features identified as “statistically significant” in the study. Such metabolic “dark matter” means that much of the potential information collected by metabolomics studies is lost. Accurate structure elucidation allows researchers to identify these compounds. This in turn, facilitates downstream metabolite pathway analysis, and a better understanding of the underlying biology of the system under investigation. This review covers a range of methods for the structural elucidation of individual compounds, including those based on gas and liquid chromatography hyphenated to mass spectrometry, single and multi-dimensional nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry and includes discussion of data standardization. Future perspectives in structure elucidation are also discussed; with a focus on the potential development of instruments and techniques, in both nuclear magnetic resonance spectroscopy and mass spectrometry that, may help solve some of the current issues that are hampering the complete identification of metabolite structure and function.

  7. Current Challenges in the Recruitment and Retention of Seafarers: An Industry Perspective from Vietnam

    Directory of Open Access Journals (Sweden)

    Trong Thanh Nguyen

    2014-08-01

    Full Text Available The shortage of seafarers (especially ship officers has already been identified as a global issue that is more likely to worsen in the immediate future. Thus, increasing attention needs to be given to the problems that hinder the effective recruitment and retention of seafarers in order to stabilize the flow of skilled labor to the global shipping industry. The aim of this paper is to discuss the seafarer shortage issue from the perspective of Vietnam which is one of the key emerging sources of crew supply in Asia. Specifically, a case study research involving the Vietnam Ocean Shipping Joint Stock Company (VOSCO is used to highlight the challenges confronting the current recruitment and retention of seafarers in Vietnam. With regards to recruitment, it was found that the low quality of graduates and trained seafarers, as well as the lack of competent onshore crew executives are pertinent issues that need to be addressed by shipping industry employers in Vietnam. In terms of retention, poor working and living conditions on-board ships is a key factor that must be given attention to improve retention among seafarers. This study recommends the development of effective human resource strategies for companies such as VOSCO and other shipping industry employers of Vietnamese seafarers in order to improve their recruitment and retention rates.

  8. A perspective on paper-based microfluidics: Current status and future trends

    Science.gov (United States)

    Li, Xu; Ballerini, David R.; Shen, Wei

    2012-01-01

    “Paper-based microfluidics” or “lab on paper,” as a burgeoning research field with its beginning in 2007, provides a novel system for fluid handling and fluid analysis for a variety of applications including health diagnostics, environmental monitoring as well as food quality testing. The reasons why paper becomes an attractive substrate for making microfluidic systems include: (1) it is a ubiquitous and extremely cheap cellulosic material; (2) it is compatible with many chemical/biochemical/medical applications; and (3) it transports liquids using capillary forces without the assistance of external forces. By building microfluidic channels on paper, liquid flow is confined within the channels, and therefore, liquid flow can be guided in a controlled manner. A variety of 2D and even 3D microfluidic channels have been created on paper, which are able to transport liquids in the predesigned pathways on paper. At the current stage of its development, paper-based microfluidic system is claimed to be low-cost, easy-to-use, disposable, and equipment-free, and therefore, is a rising technology particularly relevant to improving the healthcare and disease screening in the developing world, especially for those areas with no- or low-infrastructure and limited trained medical and health professionals. The research in paper-based microfluidics is experiencing a period of explosion; most published works have focused on: (1) inventing low-cost and simple fabrication techniques for paper-based microfluidic devices; and (2) exploring new applications of paper-based microfluidics by incorporating efficient detection methods. This paper aims to review both the fabrication techniques and applications of paper-based microfluidics reported to date. This paper also attempts to convey to the readers, from the authors’ point of view the current limitations of paper-based microfluidics which require further research, and a few perspective directions this new analytical system

  9. Altered expression of CD63 and exosomes in scleroderma dermal fibroblasts.

    Science.gov (United States)

    Nakamura, Kayo; Jinnin, Masatoshi; Harada, Miho; Kudo, Hideo; Nakayama, Wakana; Inoue, Kuniko; Ogata, Aki; Kajihara, Ikko; Fukushima, Satoshi; Ihn, Hironobu

    2016-10-01

    Exosomes are small vesicles shed from various cells. They contain proteins, lipids, and nucleic acids, and are regarded as a tool of cell-cell communication. To reveal the putative role of exosomes in systemic sclerosis (SSc), and to elucidate the effect of exosomes on wound healing. The expression of common markers for exosomes (CD63, CD9, and CD81) and type I collagen were examined with real-time PCR, immunohistochemical analysis, ELISA, immunoblotting, and flow cytometry. The effect of serum-derived exosomes on wound healing was tested on full-thickness wounds in the mid-dorsal skin of BALB/c mice. The expression levels of CD63 as well as CD9 and CD81 tended to be increased in SSc dermal fibroblasts compared to normal fibroblasts. Increased exosomes in a cultured media of SSc fibroblasts stimulated the expression levels of type I collagen in normal fibroblasts. As the mechanism, collagen-related microRNA levels in SSc fibroblast-derived exosomes were dysregulated, indicating that both the amount and the content of exosomes were altered in SSc. On the other hand, SSc sera showed significantly decreased exosome levels compared to normal sera. The frequencies of vascular involvements, including skin ulcers or pitting scars, were significantly increased in patients with decreased serum exosome levels. The healing of mice wounds was accelerated by treatment with serum-derived exosomes. Vascular abnormalities in SSc may account for the decreased serum exosome levels by the disturbed transfer of exosomes from the skin tissue to the blood stream. Our study suggests the possibility that SSc patients with vascular involvements have decreased serum exosome levels, which causes the delay of wound healing due to down-regulation of collagen, resulting in higher susceptibility to pitting scars and/or ulcers. Exosome research will lead to a detailed understanding of SSc pathogenesis and new therapeutic approaches. Copyright © 2016 Japanese Society for Investigative Dermatology

  10. Isolation and Characterization of CD34+ Blast-Derived Exosomes in Acute Myeloid Leukemia

    Science.gov (United States)

    Hong, Chang Sook; Muller, Laurent; Boyiadzis, Michael; Whiteside, Theresa L.

    2014-01-01

    Exosomes are membrane-bound vesicles found in all biological fluids. AML patients' plasma collected at diagnosis contains elevated exosome levels relative to normal donor (ND) plasma. The molecular profile of AML exosomes changes in the course of therapy and may serve as a measure of disease progression or response to therapy. However, plasma contains a mix of exosomes derived from various cell types. To be able to utilize blast-derived exosomes as biomarkers for AML, we have developed an immunoaffinity-based capture method utilizing magnetic microbeads coated with anti-CD34 antibody (Ab). This Ab is specific for CD34, a unique marker of AML blasts. The capture procedure was developed using CD34+ exosomes derived from Kasumi-1 AML cell culture supernatants. The capture capacity of CD34microbeads was shown to linearly correlate with the input exosomes. A 10 uL aliquot of CD34 microbeads was able to capture all of CD34+ exosomes present in 100–1,000 uL of AML plasma. The levels of immunocaptured CD34+ exosomes correlated with the percentages of CD34+ blasts in the AML patients' peripheral blood. The immunocaptured exosomes had a typical cup-shaped morphology by transmission electron microscopy, and their molecular cargo was similar to that of parental blasts. These exosomes were biologically-active. Upon co-incubation with natural killer (NK) cells, captured blast-derived exosomes down-regulated surface NKG2D expression, while non-captured exosomes reduced expression levels of NKp46. Our data provide a proof-of-principle that blast-derived exosomes can be quantitatively recovered from AML patients' plasma, their molecular profile recapitulates that of autologous blasts and they retain the ability to mediate immune suppression. These data suggest that immunocaptured blast-derived exosomes might be useful in diagnosis and/or prognosis of AML in the future. PMID:25093329

  11. Human vascular endothelial cells transport foreign exosomes from cow's milk by endocytosis.

    Science.gov (United States)

    Kusuma, Rio Jati; Manca, Sonia; Friemel, Taylor; Sukreet, Sonal; Nguyen, Christopher; Zempleni, Janos

    2016-05-15

    Encapsulation of microRNAs in exosomes confers protection against degradation and a vehicle for shuttling of microRNAs between cells and tissues, and cellular uptake by endocytosis. Exosomes can be found in foods including milk. Humans absorb cow's milk exosomes and deliver the microRNA cargo to peripheral tissues, consistent with gene regulation by dietary nucleic acids across species boundaries. Here, we tested the hypothesis that human vascular endothelial cells transport milk exosomes by endocytosis, constituting a step crucial for the delivery of dietary exosomes and their cargo to peripheral tissues. We tested this hypothesis by using human umbilical vein endothelial cells and fluorophore-labeled exosomes isolated from cow's milk. Exosome uptake followed Michaelis-Menten kinetics (Vmax = 0.057 ± 0.004 ng exosome protein × 40,000 cells/h; Km = 17.97 ± 3.84 μg exosomal protein/200 μl media) and decreased by 80% when the incubation temperature was lowered from 37°C to 4°C. When exosome surface proteins were removed by treatment with proteinase K, or transport was measured in the presence of the carbohydrate competitor d-galactose or measured in the presence of excess unlabeled exosomes, transport rates decreased by 45% to 80% compared with controls. Treatment with an inhibitor of endocytosis, cytochalasin D, caused a 50% decrease in transport. When fluorophore-labeled exosomes were administered retro-orbitally, exosomes accumulated in liver, spleen, and lungs in mice. We conclude that human vascular endothelial cells transport bovine exosomes by endocytosis and propose that this is an important step in the delivery of dietary exosomes and their cargo to peripheral tissues. Copyright © 2016 the American Physiological Society.

  12. Signaling Pathways in Exosomes Biogenesis, Secretion and Fate

    Directory of Open Access Journals (Sweden)

    Carla Emiliani

    2013-03-01

    Full Text Available Exosomes are small extracellular vesicles (30–100 nm derived from the endosomal system, which have raised considerable interest in the last decade. Several studies have shown that they mediate cell-to-cell communication in a variety of biological processes. Thus, in addition to cell-to-cell direct interaction or secretion of active molecules, they are now considered another class of signal mediators. Exosomes can be secreted by several cell types and retrieved in many body fluids, such as blood, urine, saliva and cerebrospinal fluid. In addition to proteins and lipids, they also contain nucleic acids, namely mRNA and miRNA. These features have prompted extensive research to exploit them as a source of biomarkers for several pathologies, such as cancer and neurodegenerative disorders. In this context, exosomes also appear attractive as gene delivery vehicles. Furthermore, exosome immunomodulatory and regenerative properties are also encouraging their application for further therapeutic purposes. Nevertheless, several issues remain to be addressed: exosome biogenesis and secretion mechanisms have not been clearly understood, and physiological functions, as well as pathological roles, are far from being satisfactorily elucidated.

  13. Exosomes as mediators of platinum resistance in ovarian cancer.

    Science.gov (United States)

    Crow, Jennifer; Atay, Safinur; Banskota, Samagya; Artale, Brittany; Schmitt, Sarah; Godwin, Andrew K

    2017-02-14

    Exosomes have been implicated in the cell-cell transfer of oncogenic proteins and genetic material. We speculated this may be one mechanism by which an intrinsically platinum-resistant population of epithelial ovarian cancer (EOC) cells imparts its influence on surrounding tumor cells. To explore this possibility we utilized a platinum-sensitive cell line, A2780 and exosomes derived from its resistant subclones, and an unselected, platinum-resistant EOC line, OVCAR10. A2780 cells demonstrate a ~2-fold increase in viability upon treatment with carboplatin when pre-exposed to exosomes from platinum-resistant cells as compared to controls. This coincided with increased epithelial to mesenchymal transition (EMT). DNA sequencing of EOC cell lines revealed previously unreported somatic mutations in the Mothers Against Decapentaplegic Homolog 4 (SMAD4) within platinum-resistant cells. A2780 cells engineered to exogenously express these SMAD4 mutations demonstrate up-regulation of EMT markers following carboplatin treatment, are more resistant to carboplatin, and release exosomes which impart a ~1.7-fold increase in resistance in naive A2780 recipient cells as compared to controls. These studies provide the first evidence that acquired SMAD4 mutations enhance the chemo-resistance profile of EOC and present a novel mechanism in which exchange of tumor-derived exosomes perpetuates an EMT phenotype, leading to the development of subpopulations of platinum-refractory cells.

  14. Molecular lipidomics of exosomes released by PC-3 prostate cancer cells

    DEFF Research Database (Denmark)

    Llorente, A.; Skotland, T.; Sylvanne, T.

    2013-01-01

    The molecular lipid composition of exosomes is largely unknown. In this study, sophisticated shotgun and targeted molecular lipidomic assays were performed for in-depth analysis of the lipidomes of the metastatic prostate cancer cell line, PC-3, and their released exosomes. This study, based...... in the quantification of approximately 280 molecular lipid species, provides the most extensive lipid analysis of cells and exosomes to date. Interestingly, major differences were found in the lipid composition of exosomes compared to parent cells. Exosomes show a remarkable enrichment of distinct lipids, demonstrating...

  15. Exosomal proteins as prognostic biomarkers in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Paulsen, Birgitte Sandfeld; Aggerholm-Pedersen, N; Bæk, R

    2016-01-01

    for optimal treatment. We here evaluate exosomes by protein phenotyping as a prognostic biomarker in NSCLC. METHODS: Exosomes from plasma of 276 NSCLC patients were phenotyped using the Extracellular Vesicle Array; 49 antibodies captured the proteins on the exosomes, and a cocktail of biotin......BACKGROUND: Use of exosomes as biomarkers in non-small cell lung cancer (NSCLC) is an intriguing approach in the liquid-biopsy era. Exosomes are nano-sized vesicles with membrane-bound proteins that reflect their originating cell. Prognostic biomarkers are needed to improve patient selection...

  16. Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis

    Science.gov (United States)

    Melo, Sonia A.; Sugimoto, Hikaru; O’Connell, Joyce T.; Kato, Noritoshi; Villanueva, Alberto; Vidal, August; Qiu, Le; Vitkin, Edward; Perelman, Lev T.; Melo, Carlos A.; Lucci, Anthony; Ivan, Cristina; Calin, George A.; Kalluri, Raghu

    2014-01-01

    SUMMARY Exosomes are secreted by all cell types and contain proteins and nucleic acids. Here, we report that breast cancer associated exosomes contain microRNAs (miRNAs) associated with the RISC Loading Complex (RLC) and display cell-independent capacity to process precursor microRNAs (pre-miRNAs) into mature miRNAs. Pre-miRNAs, along with Dicer, AGO2, and TRBP, are present in exosomes of cancer cells. CD43 mediates the accumulation of Dicer specifically in cancer exosomes. Cancer exosomes mediate an efficient and rapid silencing of mRNAs to reprogram the target cell transcriptome. Exosomes derived from cells and sera of patients with breast cancer instigate non-tumorigenic epithelial cells to form tumors in a Dicer-dependent manner. These findings offer opportunities for the development of exosomes based biomarkers and therapies. PMID:25446899

  17. Unmanned Aerial Vehicle Remote Sensing for Field-Based Crop Phenotyping: Current Status and Perspectives

    Science.gov (United States)

    Yang, Guijun; Liu, Jiangang; Zhao, Chunjiang; Li, Zhenhong; Huang, Yanbo; Yu, Haiyang; Xu, Bo; Yang, Xiaodong; Zhu, Dongmei; Zhang, Xiaoyan; Zhang, Ruyang; Feng, Haikuan; Zhao, Xiaoqing; Li, Zhenhai; Li, Heli; Yang, Hao

    2017-01-01

    Phenotyping plays an important role in crop science research; the accurate and rapid acquisition of phenotypic information of plants or cells in different environments is helpful for exploring the inheritance and expression patterns of the genome to determine the association of genomic and phenotypic information to increase the crop yield. Traditional methods for acquiring crop traits, such as plant height, leaf color, leaf area index (LAI), chlorophyll content, biomass and yield, rely on manual sampling, which is time-consuming and laborious. Unmanned aerial vehicle remote sensing platforms (UAV-RSPs) equipped with different sensors have recently become an important approach for fast and non-destructive high throughput phenotyping and have the advantage of flexible and convenient operation, on-demand access to data and high spatial resolution. UAV-RSPs are a powerful tool for studying phenomics and genomics. As the methods and applications for field phenotyping using UAVs to users who willing to derive phenotypic parameters from large fields and tests with the minimum effort on field work and getting highly reliable results are necessary, the current status and perspectives on the topic of UAV-RSPs for field-based phenotyping were reviewed based on the literature survey of crop phenotyping using UAV-RSPs in the Web of Science™ Core Collection database and cases study by NERCITA. The reference for the selection of UAV platforms and remote sensing sensors, the commonly adopted methods and typical applications for analyzing phenotypic traits by UAV-RSPs, and the challenge for crop phenotyping by UAV-RSPs were considered. The review can provide theoretical and technical support to promote the applications of UAV-RSPs for crop phenotyping. PMID:28713402

  18. Unmanned Aerial Vehicle Remote Sensing for Field-Based Crop Phenotyping: Current Status and Perspectives

    Directory of Open Access Journals (Sweden)

    Guijun Yang

    2017-06-01

    Full Text Available Phenotyping plays an important role in crop science research; the accurate and rapid acquisition of phenotypic information of plants or cells in different environments is helpful for exploring the inheritance and expression patterns of the genome to determine the association of genomic and phenotypic information to increase the crop yield. Traditional methods for acquiring crop traits, such as plant height, leaf color, leaf area index (LAI, chlorophyll content, biomass and yield, rely on manual sampling, which is time-consuming and laborious. Unmanned aerial vehicle remote sensing platforms (UAV-RSPs equipped with different sensors have recently become an important approach for fast and non-destructive high throughput phenotyping and have the advantage of flexible and convenient operation, on-demand access to data and high spatial resolution. UAV-RSPs are a powerful tool for studying phenomics and genomics. As the methods and applications for field phenotyping using UAVs to users who willing to derive phenotypic parameters from large fields and tests with the minimum effort on field work and getting highly reliable results are necessary, the current status and perspectives on the topic of UAV-RSPs for field-based phenotyping were reviewed based on the literature survey of crop phenotyping using UAV-RSPs in the Web of Science™ Core Collection database and cases study by NERCITA. The reference for the selection of UAV platforms and remote sensing sensors, the commonly adopted methods and typical applications for analyzing phenotypic traits by UAV-RSPs, and the challenge for crop phenotyping by UAV-RSPs were considered. The review can provide theoretical and technical support to promote the applications of UAV-RSPs for crop phenotyping.

  19. Unmanned Aerial Vehicle Remote Sensing for Field-Based Crop Phenotyping: Current Status and Perspectives.

    Science.gov (United States)

    Yang, Guijun; Liu, Jiangang; Zhao, Chunjiang; Li, Zhenhong; Huang, Yanbo; Yu, Haiyang; Xu, Bo; Yang, Xiaodong; Zhu, Dongmei; Zhang, Xiaoyan; Zhang, Ruyang; Feng, Haikuan; Zhao, Xiaoqing; Li, Zhenhai; Li, Heli; Yang, Hao

    2017-01-01

    Phenotyping plays an important role in crop science research; the accurate and rapid acquisition of phenotypic information of plants or cells in different environments is helpful for exploring the inheritance and expression patterns of the genome to determine the association of genomic and phenotypic information to increase the crop yield. Traditional methods for acquiring crop traits, such as plant height, leaf color, leaf area index (LAI), chlorophyll content, biomass and yield, rely on manual sampling, which is time-consuming and laborious. Unmanned aerial vehicle remote sensing platforms (UAV-RSPs) equipped with different sensors have recently become an important approach for fast and non-destructive high throughput phenotyping and have the advantage of flexible and convenient operation, on-demand access to data and high spatial resolution. UAV-RSPs are a powerful tool for studying phenomics and genomics. As the methods and applications for field phenotyping using UAVs to users who willing to derive phenotypic parameters from large fields and tests with the minimum effort on field work and getting highly reliable results are necessary, the current status and perspectives on the topic of UAV-RSPs for field-based phenotyping were reviewed based on the literature survey of crop phenotyping using UAV-RSPs in the Web of Science™ Core Collection database and cases study by NERCITA. The reference for the selection of UAV platforms and remote sensing sensors, the commonly adopted methods and typical applications for analyzing phenotypic traits by UAV-RSPs, and the challenge for crop phenotyping by UAV-RSPs were considered. The review can provide theoretical and technical support to promote the applications of UAV-RSPs for crop phenotyping.

  20. The development of dental research in Argentinean biological anthropology: current state and future perspectives.

    Science.gov (United States)

    Bernal, V; Luna, L H

    2011-10-01

    The aim of this paper is to conduct a historical analysis of the research-oriented studies related to dental anthropology in Argentina, evaluate its current state and discuss future expectations and perspectives. In this country, anthropological studies based on analysis of dentition have been scarce and even temporarily discontinued, since they began in the late nineteenth century, simply following the course of the predominant theoretical and methodological approaches over time. Early papers, guided mainly by evolutionary ideas, were oriented towards establishing the taxonomic position of humans through the description and comparison of morphological and morphometric aspects of the dental crown and root. Later studies mainly described types of intentional modifications (i.e. dental mutilations) and tooth wear in the context of Historic-Cultural School. However, they failed to constitute valid lines of research over time. In recent years, there has been a significant change in dental studies, mainly as a result of the interest in evaluating the adaptive aspects of human populations within biocultural settings. One of the most relevant lines of studies has been the bioarchaeological analysis of health and stress indicators, such as enamel hypoplasia, caries and tooth wear in hunter-gatherer and farmer societies. More recently, the study of discrete and metric dental traits began, with a goal to contribute to the study of evolution and inter-populational biological relations among South American groups. Since teeth contain valuable information not only about the environment in which the individual lived, but also about the action of neutral and non-neutral factors on human groups, the consolidation of ongoing studies will contribute to knowledge of various aspects of the adaptation and evolution of native American populations. Copyright © 2011 Elsevier GmbH. All rights reserved.

  1. The Role of Exosomal VP40 in Ebola Virus Disease.

    Science.gov (United States)

    Pleet, Michelle L; DeMarino, Catherine; Lepene, Benjamin; Aman, M Javad; Kashanchi, Fatah

    2017-04-01

    Ebola virus (EBOV) can cause a devastating hemorrhagic disease, leading to death in a short period of time. After infection, the resulting EBOV disease results in high levels of circulating cytokines, endothelial dysfunction, coagulopathy, and bystander lymphocyte apoptosis in humans and nonhuman primates. The VP40 matrix protein of EBOV is essential for viral assembly and budding from the host cell. Recent data have shown that VP40 exists in the extracellular environment, including in exosomes, and exosomal VP40 can impact the viability of recipient immune cells, including myeloid and T cells, through the regulation of the RNAi and endosomal sorting complexes required for transport pathways. In this study, we discuss the latest findings of the impact of exosomal VP40 on immune cells in vitro and its potential implications for pathogenesis in vivo.

  2. [Current perspectives on endodontic treatment of teeth with chronic periapical lesions].

    Science.gov (United States)

    Canalda Sahli, C

    1990-01-01

    The author study in this article histopathological aspects of periapical lesions, intra-granulomatous epithelial proliferation phenomenon as pathogenic mechanism of microscopic cystic cavities formation, diagnostic problems of them all, as well as the most actual therapeutic perspectives.

  3. Surveys of current status in biomedical science grant review: funding organisations' and grant reviewers' perspectives.

    Science.gov (United States)

    Schroter, Sara; Groves, Trish; Højgaard, Liselotte

    2010-10-20

    The objectives of this research were (a) to describe the current status of grant review for biomedical projects and programmes from the perspectives of international funding organisations and grant reviewers, and (b) to explore funders' interest in developing uniform requirements for grant review aimed at making the processes and practices of grant review more consistent, transparent, and user friendly. A survey to a convenience sample of 57 international public and private organisations that give grants for biomedical research was conducted. Nine participating organisations then emailed a random sample of their external reviewers an invitation to participate in a second electronic survey. A total of 28 of 57 (49%) organisations in 19 countries responded. Organisations reported these problems as frequent or very frequent: declined review requests (16), late reports (10), administrative burden (7), difficulty finding new reviewers (4), and reviewers not following guidelines (4). The administrative burden of the process was reported to have increased over the past 5 years. In all, 17 organisations supported the idea of uniform requirements for conducting grant review and for formatting grant proposals. A total of 258/418 (62%) reviewers responded from 22 countries. Of those, 48% (123/258) said their institutions encouraged grant review, yet only 7% (17/258) were given protected time and 74% (192/258) received no academic recognition for this. Reviewers rated these factors as extremely or very important in deciding to review proposals: 51% (131/258) desire to support external fairness, 47% (120/258) professional duty, 46% (118/258) relevance of the proposal's topic, 43% (110/258) wanting to keep up to date, 40% (104/258) desire to avoid suppression of innovation. Only 16% (42/258) reported that guidance from funders was very clear. In all, 85% (220/258) had not been trained in grant review and 64% (166/258) wanted this. Funders reported a growing workload of

  4. THE SOCIAL ENTERPRISE IN ROMANIA. AN EUROPEAN PERSPECTIVE ON THEIR CURRENT SITUATION

    Directory of Open Access Journals (Sweden)

    Vinke Joop

    2012-12-01

    Full Text Available The current paper is aimed at identifying the social enterprises according to EMES criteria by investigating the social economy actors in Romania. As an emerging field of study, social entrepreneurship and social enterprise have captured the attention of both practitioners from Europe and North America, and in recent years on other continents. In Romania, very little research has been conducted into the field, mostly as part of academic research papers from doctoral study students or masters, both from Romania and abroad. In Europe, several studies have been conducted among member state of the European Union, to bring to light this new emerging field.. Investigations in regard to social entrepreneurship in Europe have revealed the existence of this field among social economy actors, in the form of social enterprise, namely work integration social enterprises and social cooperatives. So far, Romania has not been included in them This papers tries to fill the gap of knowledge on this phenomena, by exploring, from a European perspective, the actors of social entrepreneurship in Romania. The methodology used was an analysis of secondary data in the form of legal documents (laws, reports of the social economy sector and scholarly articles related to social entrepreneurship in Romania. The assessment instrument is the EMES set of economic and social criteria that the social enterprises need to meet. Also, parallels have been made with the entities of the same nature in the European Union. The paper concludes on the state of social enterprise in Romania, with an underline on what its and implications for their further study. As main finding, two types of organizations fit best with the EMES criteria, authorized protected units and companies set up by associations and foundations. Also, further developments are expected as Romania is preparing for a law defining the social enterprise and social economy. The main implications of this research is drawing

  5. Role of Exosomes in Placental Homeostasis and Pregnancy Disorders.

    Science.gov (United States)

    Salomon, C; Rice, G E

    2017-01-01

    The human placenta is a unique organ that performs the function of the majority of fetal organs across gestation. How the placenta communicates with maternal tissues to prepare them for pregnancy is not fully understood. Recently, it has been established that placental cells can communicate with maternal tissues to regulate their biological function via extracellular vesicles (EVs). EVs are subclassified into exosomes or microvesicles (MVs) according to their size, cell or tissue of origin, functions, and physical features. Exosomes are a specific type of EVs from an endocytic origin, while MVs are released via budding from the plasma membrane. With regards to pregnancy, the role of EVs has been described in several functions such as immune responses and maternal metabolic adaptation to gestation. Interestingly, EVs of placental origin can be detected in a variety of body fluids including urine and blood, and have been identified in the maternal circulation at as early as 6 weeks of gestation. Moreover, the number of exosomes across gestation is higher in complications of pregnancies such as preeclampsia and gestational diabetes mellitus compared to normal pregnancies. Circulating exosomes contains proteins and RNAs that are representative of the cell of origin, including surface and cytoplasmic protein, messenger RNA, and micro-RNAs. Finally, exosomes are capable of transferring their contents to other cells and regulating the biological function of the target cell. In this review, we will discuss the effect of the maternal microenvironment on secretion and content of placenta-derived EVs, and how this may lead to complications of pregnancies with a special emphasis on exosomes. © 2017 Elsevier Inc. All rights reserved.

  6. Suppression of endothelial cell migration by tumor associated macrophage-derived exosomes is reversed by epithelial ovarian cancer exosomal lncRNA.

    Science.gov (United States)

    Wu, Quanfeng; Wu, Xiaoli; Ying, Xiang; Zhu, Qinyi; Wang, Xinjing; Jiang, Lu; Chen, Xin; Wu, Yueqian; Wang, Xipeng

    2017-01-01

    To study the mechanism by which epithelial ovarian cancer (EOC)-derived exosomes restore the migration of endothelial cells that is suppressed by TAM-derived exosomes. Exosomes were isolated from TAMs in the ascites of patients with EOC. The effect of exosomes on the expression of endothelial cell miRNA was monitored by PCR. The miRNA mimics were transfected to explore their effects. Microarray data and literature searches were used to predict target genes and the impact of target gene pathways, and small interfering RNA was used to target these genes. We used migration assays to determine whether ovarian cancer cell-derived exosomes participate in the regulation of TAMs and endothelial cells. We used microarray data to identify the target lncRNA, and we constructed target lncRNA expression plasmids to validate targets by Western blotting. We separated TAMs from the ascites of patients with EOC and isolated exosomes from TAM supernatants. After co-culture with HUVECs, these exosomes were efficiently incorporated into HUVECs. The migration of HUVECs was suppressed significantly in the exosome group compared with blank controls (P derived exosomes targeted the miR-146b-5p/TRAF6/NF-κB/MMP2 pathway to suppress endothelial cell migration; this result was supported by PCR and Western blotting analyses. The expression of exosomal miR-146b-5p isolated from serum in the EOC group was significantly increased compared to healthy individuals. Finally, TAM-derived exosomes and EOC SKOV3-derived exosomes in combination stimulated HUVEC cells and overcame the inhibition of endothelial cell migration caused by TAM-derived exosomes. Two lncRNAs that were carried by SKOV3-derived exosomes were identified as NF-κB pathway-associated genes by Western blotting. TAM-derived exosomes can inhibit the migration of endothelial cells by targeting the miR-146b-5p/TRAF6/NF-kB/MMP2 pathway. However, EOC-derived exosomes can transfer lncRNAs to remotely reverse this effect of TAMs on

  7. High-resolution proteomic and lipidomic analysis of exosomes and microvesicles from different cell sources

    Directory of Open Access Journals (Sweden)

    Reka A. Haraszti

    2016-11-01

    Full Text Available Extracellular vesicles (EVs, including exosomes and microvesicles (MVs, are explored for use in diagnostics, therapeutics and drug delivery. However, little is known about the relationship of protein and lipid composition of EVs and their source cells. Here, we report high-resolution lipidomic and proteomic analyses of exosomes and MVs derived by differential ultracentrifugation from 3 different cell types: U87 glioblastoma cells, Huh7 hepatocellular carcinoma cells and human bone marrow-derived mesenchymal stem cells (MSCs. We identified 3,532 proteins and 1,961 lipid species in the screen. Exosomes differed from MVs in several different areas: (a The protein patterns of exosomes were more likely different from their cells of origin than were the protein patterns of MVs; (b The proteomes of U87 and Huh7 exosomes were similar to each other but different from the proteomes of MSC exosomes, whereas the lipidomes of Huh7 and MSC exosomes were similar to each other but different from the lipidomes of U87 exosomes; (c exosomes exhibited proteins of extracellular matrix, heparin-binding, receptors, immune response and cell adhesion functions, whereas MVs were enriched in endoplasmic reticulum, proteasome and mitochondrial proteins. Exosomes and MVs also differed in their types of lipid contents. Enrichment in glycolipids and free fatty acids characterized exosomes, whereas enrichment in ceramides and sphingomyelins characterized MVs. Furthermore, Huh7 and MSC exosomes were specifically enriched in cardiolipins; U87 exosomes were enriched in sphingomyelins. This study comprehensively analyses the protein and lipid composition of exosomes, MVs and source cells in 3 different cell types.

  8. Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation

    Energy Technology Data Exchange (ETDEWEB)

    Hazawa, Masaharu; Tomiyama, Kenichi; Saotome-Nakamura, Ai; Obara, Chizuka; Yasuda, Takeshi; Gotoh, Takaya; Tanaka, Izumi; Yakumaru, Haruko; Ishihara, Hiroshi; Tajima, Katsushi, E-mail: tajima@nirs.go.jp

    2014-04-18

    Highlights: • Radiation increases cellular uptake of exosomes. • Radiation induces colocalization of CD29 and CD81. • Exosomes selectively bind the CD29/CD81 complex. • Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation. - Abstract: Exosomes mediate intercellular communication, and mesenchymal stem cells (MSC) or their secreted exosomes affect a number of pathophysiologic states. Clinical applications of MSC and exosomes are increasingly anticipated. Radiation therapy is the main therapeutic tool for a number of various conditions. The cellular uptake mechanisms of exosomes and the effects of radiation on exosome–cell interactions are crucial, but they are not well understood. Here we examined the basic mechanisms and effects of radiation on exosome uptake processes in MSC. Radiation increased the cellular uptake of exosomes. Radiation markedly enhanced the initial cellular attachment to exosomes and induced the colocalization of integrin CD29 and tetraspanin CD81 on the cell surface without affecting their expression levels. Exosomes dominantly bound to the CD29/CD81 complex. Knockdown of CD29 completely inhibited the radiation-induced uptake, and additional or single knockdown of CD81 inhibited basal uptake as well as the increase in radiation-induced uptake. We also examined possible exosome uptake processes affected by radiation. Radiation-induced changes did not involve dynamin2, reactive oxygen species, or their evoked p38 mitogen-activated protein kinase-dependent endocytic or pinocytic pathways. Radiation increased the cellular uptake of exosomes through CD29/CD81 complex formation. These findings provide essential basic insights for potential therapeutic applications of exosomes or MSC in combination with radiation.

  9. Exosomes Derived from Mesenchymal Stromal Cells Promote Axonal Growth of Cortical Neurons.

    Science.gov (United States)

    Zhang, Yi; Chopp, Michael; Liu, Xian Shuang; Katakowski, Mark; Wang, Xinli; Tian, Xinchu; Wu, David; Zhang, Zheng Gang

    2017-05-01

    Treatment of brain injury with exosomes derived from mesenchymal stromal cells (MSCs) enhances neurite growth. However, the direct effect of exosomes on axonal growth and molecular mechanisms underlying exosome-enhanced neurite growth are not known. Using primary cortical neurons cultured in a microfluidic device, we found that MSC-exosomes promoted axonal growth, whereas attenuation of argonaut 2 protein, one of the primary microRNA (miRNA) machinery proteins, in MSC-exosomes abolished their effect on axonal growth. Both neuronal cell bodies and axons internalized MSC-exosomes, which was blocked by botulinum neurotoxins (BoNTs) that cleave proteins of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. Moreover, tailored MSC-exosomes carrying elevated miR-17-92 cluster further enhanced axonal growth compared to native MSC-exosomes. Quantitative RT-PCR and Western blot analysis showed that the tailored MSC-exosomes increased levels of individual members of this cluster and activated the PTEN/mTOR signaling pathway in recipient neurons, respectively. Together, our data demonstrate that native MSC-exosomes promote axonal growth while the tailored MSC-exosomes can further boost this effect and that tailored exosomes can deliver their selective cargo miRNAs into and activate their target signals in recipient neurons. Neuronal internalization of MSC-exosomes is mediated by the SNARE complex. This study reveals molecular mechanisms that contribute to MSC-exosome-promoted axonal growth, which provides a potential therapeutic strategy to enhance axonal growth.

  10. The human core exosome interacts with differentially localized processive RNases

    DEFF Research Database (Denmark)

    Tomecki, Rafal; Kristiansen, Maiken Søndergaard; Lykke-Andersen, Søren

    2010-01-01

    The eukaryotic RNA exosome is a ribonucleolytic complex involved in RNA processing and turnover. It consists of a nine-subunit catalytically inert core that serves a structural function and participates in substrate recognition. Best defined in Saccharomyces cerevisiae, enzymatic activity comes......, identity and arrangements of its catalytic subunits in different vertebrates remain elusive. Here, we demonstrate the association of two different Dis3p homologs--hDIS3 and hDIS3L--with the human exosome core. Interestingly, these factors display markedly different intracellular localizations: hDIS3...

  11. Exosomal MicroRNA-15a Transfer from the Pancreas Augments Diabetic Complications by Inducing Oxidative Stress.

    Science.gov (United States)

    Kamalden, Tengku Ain; Macgregor-Das, Anne M; Kannan, Sangeetha Marimuthu; Dunkerly-Eyring, Brittany; Khaliddin, Nurliza; Xu, Zhenhua; Fusco, Anthony P; Yazib, Syatirah Abu; Chow, Rhuen Chiou; Duh, Elia J; Halushka, Marc K; Steenbergen, Charles; Das, Samarjit

    2017-11-01

    MicroRNAs (miRNAs), one type of noncoding RNA, modulate post-transcriptional gene expression in various pathogenic pathways in type 2 diabetes (T2D). Currently, little is known about how miRNAs influence disease pathogenesis by targeting cells at a distance. The purpose of this study was to investigate the role of exosomal miRNAs during T2D. We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic β-cells. By culturing rat pancreatic β-cells (INS-1) cells in high-glucose media, we identified a source of increased miR-15a in the blood as exosomes secreted by pancreatic β-cells. We postulate that miR-15a, produced in pancreatic β-cells, can enter the bloodstream and contribute to retinal injury. miR-15a overexpression in Müller cells can be induced by exposing Müller cells to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death. The in vivo relevance of these findings is supported by results from high-fat diet and pancreatic β-cell-specific miR-15a -/- mice. This study highlights an important and underappreciated mechanism of remote cell-cell communication (exosomal transfer of miRNA) and its influence on the development of T2D complications. Our findings suggest that circulating miR-15a contributes to the pathogenesis of diabetes and supports the concept that miRNAs released by one cell type can travel through the circulation and play a role in disease progression via their transfer to different cell types, inducing oxidative stress and cell injury. Antioxid. Redox Signal. 27, 913-930.

  12. RRP42, a Subunit of Exosome, Plays an Important Role in Female Gametophytes Development and Mesophyll Cell Morphogenesis in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Xiaoyuan Yan

    2017-06-01

    Full Text Available The exosome complex plays a central and essential role in RNA metabolism. However, current research on functions of exosome subunit in plants is limited. Here, we used an egg cell-specific promoter-controlled CRISPR/Cas9 system to knock out RRP42 which encodes a core subunit of the Arabidopsis exosome and presented evidence that RRP42 is essential for the development of female gametophytes. Next, we designed three different amiRNAs targeting RRP42. The rrp42 knock-down mutants mainly displayed variegated and serrated leaves, especially in cauline leaves. The internal anatomy of cauline leaves displayed irregularly shaped palisade cells and a reduced density of mesophyll cells. Interestingly, we detected highly accumulated mRNAs that encode xyloglucan endotransglucosylase/hydrolases (XTHs and expansins (EXPAs during later growth stages in rrp42 knock-down mutants. The mRNA decay kinetics analysis for XTH19, EXPA10, and EXPA11 revealed that RRP42 had a role in the decay of these mRNAs in the cytoplasm. RRP42 is localized to both the nucleus and cytoplasm, and RRP42 is preferentially expressed in cauline leaves during later growth stages. Altogether, our results demonstrate that RRP42 is essential for the development of female gametophytes and plays an important role in mesophyll cell morphogenesis.

  13. Exosomal and Non-Exosomal Transport of Extra-Cellular microRNAs in Follicular Fluid: Implications for Bovine Oocyte Developmental Competence.

    Directory of Open Access Journals (Sweden)

    Md Mahmodul Hasan Sohel

    Full Text Available Cell-cell communication within the follicle involves many signaling molecules, and this process may be mediated by secretion and uptake of exosomes that contain several bioactive molecules including extra-cellular miRNAs. Follicular fluid and cells from individual follicles of cattle were grouped based on Brilliant Cresyl Blue (BCB staining of the corresponding oocytes. Both Exoquick precipitation and differential ultracentrifugation were used to separate the exosome and non-exosomal fraction of follicular fluid. Following miRNA isolation from both fractions, the human miRCURY LNA™ Universal RT miRNA PCR array system was used to profile miRNA expression. This analysis found that miRNAs were present in both exosomal and non-exosomal fraction of bovine follicular fluid. We found 25 miRNAs differentially expressed (16 up and 9 down in exosomes and 30 miRNAs differentially expressed (21 up and 9 down in non-exosomal fraction of follicular fluid in comparison of BCB- versus BCB+ oocyte groups. Expression of selected miRNAs was detected in theca, granulosa and cumulus oocyte complex. To further explore the potential roles of these follicular fluid derived extra-cellular miRNAs, the potential target genes were predicted, and functional annotation and pathway analysis revealed most of these pathways are known regulators of follicular development and oocyte growth. In order to validate exosome mediated cell-cell communication within follicular microenvironment, we demonstrated uptake of exosomes and resulting increase of endogenous miRNA level and subsequent alteration of mRNA levels in follicular cells in vitro. This study demonstrates for the first time, the presence of exosome or non-exosome mediated transfer of miRNA in the bovine follicular fluid, and oocyte growth dependent variation in extra-cellular miRNA signatures in the follicular environment.

  14. Cisplatin-resistant lung cancer cell-derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100-5p-dependent manner.

    Science.gov (United States)

    Qin, Xiaobing; Yu, Shaorong; Zhou, Leilei; Shi, Meiqi; Hu, Yong; Xu, Xiaoyue; Shen, Bo; Liu, Siwen; Yan, Dali; Feng, Jifeng

    2017-01-01

    Exosomes derived from lung cancer cells confer cisplatin (DDP) resistance to other cancer cells. However, the underlying mechanism is still unknown. A549 resistance to DDP (A549/DDP) was established. Microarray was used to analyze microRNA (miRNA) expression profiles of A549 cells, A549/DDP cells, A549 exosomes, and A549/DDP exosomes. There was a strong correlation of miRNA profiles between exosomes and their maternal cells. A total of 11 miRNAs were significantly upregulated both in A549/DDP cells compared with A549 cells and in exosomes derived from A549/DDP cells in contrast to exosomes from A549 cells. A total of 31 downregulated miRNAs were also observed. miR-100-5p was the most prominent decreased miRNA in DDP-resistant exosomes compared with the corresponding sensitive ones. Downregulated miR-100-5p was proved to be involved in DDP resistance in A549 cells, and mammalian target of rapamycin (mTOR) expression was reverse regulated by miR-100-5p. Exosomes confer recipient cells' resistance to DDP in an exosomal miR-100-5p-dependent manner with mTOR as its potential target both in vitro and in vivo. Exosomes from DDP-resistant lung cancer cells A549 can alter other lung cancer cells' sensitivity to DDP in exosomal miR-100-5p-dependent manner. Our study provides new insights into the molecular mechanism of DDP resistance in lung cancer.

  15. Identification of archaeal proteins that affect the exosome function in vitro

    Directory of Open Access Journals (Sweden)

    Palhano Fernando L

    2010-05-01

    Full Text Available Abstract Background The archaeal exosome is formed by a hexameric RNase PH ring and three RNA binding subunits and has been shown to bind and degrade RNA in vitro. Despite extensive studies on the eukaryotic exosome and on the proteins interacting with this complex, little information is yet available on the identification and function of archaeal exosome regulatory factors. Results Here, we show that the proteins PaSBDS and PaNip7, which bind preferentially to poly-A and AU-rich RNAs, respectively, affect the Pyrococcus abyssi exosome activity in vitro. PaSBDS inhibits slightly degradation of a poly-rA substrate, while PaNip7 strongly inhibits the degradation of poly-A and poly-AU by the exosome. The exosome inhibition by PaNip7 appears to depend at least partially on its interaction with RNA, since mutants of PaNip7 that no longer bind RNA, inhibit the exosome less strongly. We also show that FITC-labeled PaNip7 associates with the exosome in the absence of substrate RNA. Conclusions Given the high structural homology between the archaeal and eukaryotic proteins, the effect of archaeal Nip7 and SBDS on the exosome provides a model for an evolutionarily conserved exosome control mechanism.

  16. Saliva exosomes from pancreatic tumor-bearing mice modulate NK cell phenotype and antitumor cytotoxicity.

    Science.gov (United States)

    Katsiougiannis, Stergios; Chia, David; Kim, Yong; Singh, Ram P; Wong, David T W

    2017-03-01

    Tumor exosomes are emerging as antitumor immunity regulators; however, their effects on secondary exosome secretion by distal organs have not been explored. We have previously demonstrated that suppression of exosomes at the distal tumor site of pancreatic ductal adenocarcinoma (PDAC) ablated the development of salivary biomarker profile. Here, we explore the function of salivary exosomes from tumor-bearing mice in immune surveillance. We provide evidence that salivary exosomes from mice with PDAC exhibit a suppressive effect that results in reduced tumor-killing capacity by NK cells. Salivary exosomes from mice with PDAC where pancreatic tumors were engineered to suppress exosome biogenesis failed to suppress NK cell cytotoxic potential against tumor cells, as opposed to salivary exosomes from mice with PDAC with normal tumor exosome biogenesis. These results reveal an important and previously unknown mechanism of antitumor immune regulation and provide new insights into our understanding of the alterations of this biofluid during tumor development.-Katsiougiannis, S., Chia, D., Kim, Y., Singh, R. P., Wong, D. T. W. Saliva exosomes from pancreatic tumor-bearing mice modulate NK cell phenotype and antitumor cytotoxicity. © FASEB.

  17. Neutrophil-Derived Exosomes: A New Mechanism Contributing to Airway Smooth Muscle Remodeling.

    Science.gov (United States)

    Vargas, Amandine; Roux-Dalvai, Florence; Droit, Arnaud; Lavoie, Jean-Pierre

    2016-09-01

    Neutrophils infiltrate the airways of patients with asthma of all severities, yet their role in the pathogenesis of asthma and their contribution to airway remodeling is largely unknown. We hypothesized that neutrophils modulate airway smooth muscle (ASM) proliferation in asthma by releasing bioactive exosomes. These newly discovered nano-sized vesicles have the capacity to modulate immune responses, cell migration, cell differentiation, and other aspects of cell-to-cell communication. The aim of the study is to determine whether bioactive exosomes are released by neutrophils, and, if so, characterize their proteomic profile and evaluate their capacity to modulate ASM cell proliferation. Exosomes were isolated from equine neutrophil supernatants by differential centrifugation and filtration methods, followed by size-exclusion chromatography. Nanovesicles were characterized using electron microscopy, particle size determination, and proteomic analyses. Exosomes were cocultured with ASM cells and analyzed for exosome internalization by confocal microscopy. ASM proliferation was measured using an impedance-based system. Neutrophils release exosomes that have characteristic size, morphology, and exosomal markers. We identified 271 proteins in exosomes from both LPS and unstimulated neutrophils, and 16 proteins that were differentially expressed, which carried proteins associated with immune response and positive regulation of cell communication. Furthermore, neutrophil-derived exosomes were rapidly internalized by ASM cells and altered their proliferative properties. Upon stimulation of LPS, neutrophil-derived exosomes can enhance the proliferation of ASM cells and could therefore play an important role in the progression of asthma and promoting airway remodeling in severe and corticosteroid-insensitive patients with asthma.

  18. Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Relieve Acute Myocardial Ischemic Injury

    Directory of Open Access Journals (Sweden)

    Yuanyuan Zhao

    2015-01-01

    Full Text Available This study is aimed at investigating whether human umbilical cord mesenchymal stem cell- (hucMSC- derived exosomes (hucMSC-exosomes have a protective effect on acute myocardial infarction (AMI. Exosomes were characterized under transmission electron microscopy and the particles of exosomes were further examined through nanoparticle tracking analysis. Exosomes (400 μg protein were intravenously administrated immediately following ligation of the left anterior descending (LAD coronary artery in rats. Cardiac function was evaluated by echocardiography and apoptotic cells were counted using TUNEL staining. The cardiac fibrosis was assessed using Masson’s trichrome staining. The Ki67 positive cells in ischemic myocardium were determined using immunohistochemistry. The effect of hucMSC-exosomes on blood vessel formation was evaluated through tube formation and migration of human umbilical vein endothelial cells (EA.hy926 cells. The results indicated that ligation of the LAD coronary artery reduced cardiac function and induced cardiomyocyte apoptosis. Administration of hucMSC-exosomes significantly improved cardiac systolic function and reduced cardiac fibrosis. Moreover, hucMSC-exosomes protected myocardial cells from apoptosis and promoted the tube formation and migration of EA.hy926 cells. It is concluded that hucMSC-exosomes improved cardiac systolic function by protecting myocardial cells from apoptosis and promoting angiogenesis. These effects of hucMSC-exosomes might be associated with regulating the expression of Bcl-2 family.

  19. Exosome production and its regulation of EGFR during wound healing in renal tubular cells.

    Science.gov (United States)

    Zhou, Xiangjun; Zhang, Wei; Yao, Qisheng; Zhang, Hao; Dong, Guie; Zhang, Ming; Liu, Yutao; Chen, Jian-Kang; Dong, Zheng

    2017-06-01

    Kidney repair following injury involves the reconstitution of a structurally and functionally intact tubular epithelium. Growth factors and their receptors, such as EGFR, are important in the repair of renal tubules. Exosomes are cell-produced small (~100 nm in diameter) vesicles that contain and transfer proteins, lipids, RNAs, and DNAs between cells. In this study, we examined the relationship between exosome production and EGFR activation and the potential role of exosome in wound healing. EGFR activation occurred shortly after scratch wounding in renal tubular cells. Wound repair after scratching was significantly promoted by EGF and suppressed by EGFR inhibitor gefitinib. Interestingly, scratch wounding induced a significant increase of exosome production. The exosome production was decreased by EGF and increased by gefitinib, suggesting a suppressive role of EGFR signaling in exosome production. Conversely, inhibition of exosome release by GW4869 and manumycin A markedly increased EGFR activation and promoted wound healing. Moreover, exosomes derived from scratch-wounding cells could inhibit wound healing. Collectively, the results indicate that wound healing in renal tubular cells is associated with EGFR activation and exosome production. Although EGFR activation promotes wound healing, released exosomes may antagonize EGFR activation and wound healing. Copyright © 2017 the American Physiological Society.

  20. Isolation of exosomes from whole blood by integrating acoustics and microfluidics.

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    Wu, Mengxi; Ouyang, Yingshi; Wang, Zeyu; Zhang, Rui; Huang, Po-Hsun; Chen, Chuyi; Li, Hui; Li, Peng; Quinn, David; Dao, Ming; Suresh, Subra; Sadovsky, Yoel; Huang, Tony Jun

    2017-10-03

    Exosomes are nanoscale extracellular vesicles that play an important role in many biological processes, including intercellular communications, antigen presentation, and the transport of proteins, RNA, and other molecules. Recently there has been significant interest in exosome-related fundamental research, seeking new exosome-based biomarkers for health monitoring and disease diagnoses. Here, we report a separation method based on acoustofluidics (i.e., the integration of acoustics and microfluidics) to isolate exosomes directly from whole blood in a label-free and contact-free manner. This acoustofluidic platform consists of two modules: a microscale cell-removal module that first removes larger blood components, followed by extracellular vesicle subgroup separation in the exosome-isolation module. In the cell-removal module, we demonstrate the isolation of 110-nm particles from a mixture of micro- and nanosized particles with a yield greater than 99%. In the exosome-isolation module, we isolate exosomes from an extracellular vesicle mixture with a purity of 98.4%. Integrating the two acoustofluidic modules onto a single chip, we isolated exosomes from whole blood with a blood cell removal rate of over 99.999%. With its ability to perform rapid, biocompatible, label-free, contact-free, and continuous-flow exosome isolation, the integrated acoustofluidic device offers a unique approach to investigate the role of exosomes in the onset and progression of human diseases with potential applications in health monitoring, medical diagnosis, targeted drug delivery, and personalized medicine.

  1. A gestational profile of placental exosomes in maternal plasma and their effects on endothelial cell migration.

    Directory of Open Access Journals (Sweden)

    Carlos Salomon

    Full Text Available Studies completed to date provide persuasive evidence that placental cell-derived exosomes play a significant role in intercellular communication pathways that potentially contribute to placentation and development of materno-fetal vascular circulation. The aim of this study was to establish the gestational-age release profile and bioactivity of placental cell-derived exosome in maternal plasma. Plasma samples (n = 20 per pregnant group were obtained from non-pregnant and pregnant women in the first (FT, 6-12 weeks, second (ST, 22-24 weeks and third (TT, 32-38 weeks trimester. The number of exosomes and placental exosome contribution were determined by quantifying immunoreactive exosomal CD63 and placenta-specific marker (PLAP, respectively. The effect of exosomes isolated from FT, ST and TT on endothelial cell migration were established using a real-time, live-cell imaging system (Incucyte. Exosome plasma concentration was more than 50-fold greater in pregnant women than in non-pregnant women (p<0.001. During normal healthy pregnancy, the number of exosomes present in maternal plasma increased significantly with gestational age by more that two-fold (p<0.001. Exosomes isolated from FT, ST and TT increased endothelial cell migration by 1.9±0.1, 1.6±0.2 and 1.3±0.1-fold, respectively compared to the control. Pregnancy is associated with a dramatic increase in the number of exosomes present in plasma and maternal plasma exosomes are bioactive. While the role of placental cell-derived exosome in regulating maternal and/or fetal vascular responses remains to be elucidated, changes in exosome profile may be of clinical utility in the diagnosis of placental dysfunction.

  2. Chondroitin sulfate proteoglycan serglycin influences protein cargo loading and functions of tumor-derived exosomes.

    Science.gov (United States)

    Purushothaman, Anurag; Bandari, Shyam K; Chandrashekar, Darshan S; Jones, Richard J; Lee, Hans C; Weber, Donna M; Orlowski, Robert Z

    2017-09-26

    Tumor cells produce and utilize exosomes to promote tumor growth and metastasis. Tumor-cell-derived exosomes deliver cargos that partially mimic the contents of the parent cell to nearby or distant normal or abnormal cells, thereby reprogramming the recipient cells to support tumor progression. Mechanisms by which tumor-derived exosomes subserve the tumor are under intense investigation. Here we demonstrate a critical role of the chondroitin sulfate proteoglycan serglycin in regulating the protein cargo and functions of myeloma cell-derived exosomes. Previous studies have shown that serglycin, the only known intracellular proteoglycan, functions mainly in the storage of basically charged components within the intracellular granules/vesicles via serglycin's densely clustered, negatively charged glycosaminoglycan chains. Here we demonstrate that serglycin plays a critical role in the protein cargo loading of tumor-derived exosomes. Serglycin was detected in exosomes derived from cell culture supernatants of human myeloma cell lines and serum of myeloma patients. Mass spectrometry analysis of exosomal proteins identified significantly fewer protein components within exosomes derived from serglycin-knockdown myeloma cells than within exosomes from control cells. On gene ontology analysis, exosomes derived from serglycin-knockdown cells, but not from control cells, lacked many proteins that are required for mediating different cellular processes. In functional assays, exosomes from serglycin-knockdown cells failed to induce an invasive phenotype in myeloma cells and failed to promote migration of macrophages. These findings reveal that serglycin plays an important role in maintaining the protein cargo in tumor-derived exosomes and suggest that targeting serglycin may temper the influence of these exosomes on cancer progression.

  3. Functional significance of macrophage-derived exosomes in inflammation and pain.

    Science.gov (United States)

    McDonald, Marguerite K; Tian, Yuzhen; Qureshi, Rehman A; Gormley, Michael; Ertel, Adam; Gao, Ruby; Aradillas Lopez, Enrique; Alexander, Guillermo M; Sacan, Ahmet; Fortina, Paolo; Ajit, Seena K

    2014-08-01

    Exosomes, secreted microvesicles transporting microRNAs (miRNAs), mRNAs, and proteins through bodily fluids, facilitate intercellular communication and elicit immune responses. Exosomal contents vary, depending on the source and the physiological conditions of cells, and can provide insights into how cells and systems cope with physiological perturbations. Previous analysis of circulating miRNAs in patients with complex regional pain syndrome (CRPS), a debilitating chronic pain disorder, revealed a subset of miRNAs in whole blood that are altered in the disease. To determine functional consequences of alterations in exosomal biomolecules in inflammation and pain, we investigated exosome-mediated information transfer in vitro, in a rodent model of inflammatory pain, and in exosomes from patients with CRPS. Mouse macrophage cells stimulated with lipopolysaccharides secrete exosomes containing elevated levels of cytokines and miRNAs that m