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Chapter 5 Mercury Tonics (Rasāyana) in Sanskrit Medical Literature (Book chapter)

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ISBN: 9781781791288 9781781791288 9781781791295 9781781794364 9781781794371 Year: Pages: 21 Language: English
Publisher: Equinox Grant: H2020 European Research Council - 639363
Subject: Medicine (General) --- History
Added to DOAB on : 2019-01-15 13:34:35
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This chapter will provide a brief survey of the uses of mercury preparations&#xD;in rasāyana therapy, discussing their position within rejuvenation&#xD;therapy in regard to other rasāyana formulations and exploring their link&#xD;with Indian alchemical traditions.

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History --- Indian medicine --- therapy

Hallucinations: New Interventions Supporting People with Distressing Voices and/or Visions

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450077 Year: Pages: 106 DOI: 10.3389/978-2-88945-007-7 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Psychology
Added to DOAB on : 2018-02-27 16:16:44
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Hallucinations can occur across the five sensory modalities (auditory, visual, olfactory, tactile, and gustatory). Whilst they have the potential to be benign or even highly valued, they can often be devastating experiences associated with distress, impaired social and occupational functioning, self-harm and suicide. Those who experience hallucinations in this latter manner may do so within the context of a wide range of psychiatric diagnoses, including schizophrenia, bipolar disorder, borderline personality disorder, and post-traumatic stress disorder. The only routinely available interventions for people distressed by hallucinations are antipsychotic drugs, which date from the introduction of chlorpromazine in the 1950s, and manualized cognitive behavioral therapy, which originated in the 1990s. These interventions do not help all people distressed by hallucinations, and in the case of antipsychotic medication, come with notable side-effects. There has hence been great interest in new interventions to support people distressed by hallucinations. The goal of this Frontiers Research Topic is to present a collection of papers on new developments in clinical interventions for those distressed by hallucinations. In the psychiatric condition that remains most strongly associated with hallucinations, schizophrenia, the majority (~70%) of people will have experienced hallucinations in the auditory modality, approximately a third will have experienced visual hallucinations, and a smaller minority will have experienced hallucinations in other modalities. Consistent with this prevalence, this collection focusses on auditory and visual hallucinations. This is not to minimise the potential distress that can occur from hallucinations in other modalities. For example, tactile hallucinations, particularly when stemming from earlier experiences of sexual abuse, can be highly distressing, and improved ways to help sufferers of such experiences are also needed. In summary, this collection aims to result in an interdisciplinary collection of papers which will appeal to a wide readership, spanning all with an interest in this area.

Interaction Between Hyaluronic Acid and Its Receptors (CD44, RHAMM) Regulates the Activity of Inflammation and Cancer

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199136 Year: Pages: 218 DOI: 10.3389/978-2-88919-913-6 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2016-01-19 14:05:46
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The biological outcome of Hyaluronan (also hyaluronic acid, abbreviated HA) interaction with its CD44 or RHAMM receptors recently attracted much attention within the scientific community owing to a Nature article by Tian X et al. (Nature 2013; 499:346-9). The article described a life span exceeding 30 years in naked mole rats, whereas the maximal lifespan of mice, to which the naked mole rat is related, is only 4 years. This observation is accompanied by the finding that the naked mole rat, in contrast to the mouse, does not develop spontaneous tumors during this exceptional longevity. The article provides evidence that interaction of long tissue HA (6000-12,000 kDa) of the naked mole rat with cell surface CD44, in contrast to the interaction of short tissue HA (less than 3000 kDa) with the mouse CD44, makes the difference. More specifically, this communication shows that the interaction of short HA with fibroblasts’ CD44 imposes on them susceptibility for malignant transformation, whereas the corresponding interaction with long HA imposes on the fibroblasts a resistance to malignant transformation. The article does not explain the mechanism that underlines these findings. However, the articles, that will be published in the proposed Research Topic in the Inflammation section of Frontiers in Immunology, can bridge not only this gap, but also may explain why interaction between short HA and cell surface CD44 (or RHAMM, an additional HA receptor) enhances the development of inflammatory and malignant diseases. Furthermore, the articles included in the proposed Frontiers Research Topic will show that cancer cells and inflammatory cells share several properties related to the interaction between short HA and cell surface CD44 and/or RHAMM. These shared properties include: 1. Support of cell migration, which allows tumor metastasis and accumulation of inflammatory cells at the inflammation site; 2. Delivery of intracellular signaling, which leads to cell survival of either cancer cells or inflammatory cells; 3. Delivery of intracellular signaling, which activates cell replication and population expansion of either cancer cells or inflammatory cells; and 4. Binding of growth factors to cell surface CD44 of cancer cells or inflammatory cells (i.e., the growth factors) and their presentation to cells with cognate receptors (endothelial cells, fibroblasts), leading to pro-malignant or pro-inflammatory activities. Going back to the naked mole rat story, we may conclude from the proposed articles of this Frontiers Research Topic that the long HA, which displays anti-malignant effect, interferes with the above described pro-malignant potential of the short HA (perhaps by competing on the same CD44 receptor). Extrapolating this concept to Inflammation, the same mechanism (competition?) may be valid for inflammatory (and autoimmune) activities. If this is the case, long HA may be used for therapy of both malignant and inflammatory diseases. Moreover, targeting the interaction between short HA and CD44 (e.g. by anti-CD44 blocking antibodies) may display also a therapeutic effect on both malignant and inflammatory diseases, an issue that encourages not only fruitful exchange of views, but also practical experimental collaboration.

Fetal Therapies and Maternal-Fetal Tolerance

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199839 Year: Pages: 84 DOI: 10.3389/978-2-88919-983-9 Language: English
Publisher: Frontiers Media SA
Subject: Therapeutics --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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The ability to diagnose and treat genetic diseases before birth represents one of the foremost breakthroughs of modern medicine. While fetal surgery has advanced in the last several decades, the prospect of applying developments in stem cell biology and gene therapy to the fetal environment remains an open frontier. This issue represents the work of international experts in the field of fetal therapy, who came together at the first meeting of the International Fetal Transplantation and Immunology Society in 2014. This meeting was convened in an effort to provide a consensus for future applications of in utero transplantation and gene therapy, as well as form an international community of colleagues to nurture this field.

Biology-Driven Targeted Therapy of Pediatric Soft-Tissue and Bone Tumors: Current Opportunities and Future Challenges

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198191 Year: Pages: 147 DOI: 10.3389/978-2-88919-819-1 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Medicine (General)
Added to DOAB on : 2016-01-19 14:05:46
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Recent advances in the understanding of the biological basis of pediatric soft-tissue and bone tumors, especially owing to the advent of “omics” technologies, have led to an exponential increase in the current knowledge on the genetic and cellular patho-mechanisms that drive these diseases. This offers the unprecedented opportunity to develop and implement targeted therapies such as monoclonal antibodies, small molecules, oncolytic viruses, and immunotherapies in standard and/or personalized treatment regimens. However, to date only a few examples document a successful translation of discoveries from the bench to the bedside. Recent international expert congresses such as the “Pediatric Cancer Translational Genomics” conference (Phoenix, Arizona, 2012), the ESF-EMBO workshop on “Molecular Biology and Innovative Therapies in Sarcomas” (Pultusk, Poland, 2012), and the AACR special meeting on “Pediatric Cancer at the Crossroads – Translating Discovery into Improved Outcomes” (San Diego, California, 2013) further emphasize the urgent need for a more rapid and especially more successful translational process. Hence, we strongly believe that a Frontiers Research Topic aiming at this aspect would fit just in time and that it would have great potential to receive numerous contributions of outstanding experts of the field. The proposed Frontiers Research Topic shall provide a platform for active and interdisciplinary discussion, summarize current state-of-the-art knowledge on all basic research and translational aspects in pediatric soft-tissue and bone tumors, and offer new perspectives of how to further promote and accelerate the translational process. We welcome high-quality original research articles, brief reports, as well as opinion, hypothesis, and review articles, and especially encourage submissions from early-career scientists.

NK Cell-Based Cancer Immunotherapy

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199341 Year: Pages: 222 DOI: 10.3389/978-2-88919-934-1 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2016-01-19 14:05:46
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Natural killer (NK) cells are innate lymphoid cells that have a significant role in regulating the defenses against cancer development and certain viral infections. They are equipped with an array of activating and inhibitory receptors that stimulate or diminish NK cell activity, respectively. Inhibitory receptors include, among others, the MHC class I ligands killer cell immunoglobulin-like receptors (KIR) in humans, and members of the Ly49 family of receptors in mice, and CD94/NKG2A. Activating receptors include cytokine and chemokine receptors, and those that interact with ligands expressed on target cells, such as the natural cytotoxicity receptors or NCRs (NKp30, NKp44 and NKp46), NKG2D, CD244 and DNAM-1. In addition, NK cells express Fc?RIIIA or CD16, the receptor that exerts antibody-dependent cell mediated cytotoxicity (ADCC). NK cells also express the death ligands FasL and TRAIL. The killing or sparing of target cells depends on the integration of distinct signals that originate from NK cell receptors. NK cells spare healthy cells that express normal levels of MHC class I molecules and low amounts of stress-induced self-molecules, whereas they kill target cells that down-regulate MHC class I molecules and/or up-regulate stress-induced self-molecules. The latter are common signatures of virus-infected cells and tumors. All the accumulated knowledge on NK cell biology, along with many clinical observations, is driving multiple efforts to improve the arsenal of NK cell-based therapeutic tools in the fight against malignant diseases. Indeed, NK cell-based immunotherapy is becoming a promising approach for the treatment of many cancers. It is well known that NK cells have a significant role in the anti-tumor effect of therapeutic antibodies that use ADCC as a mechanism of action. In addition to this, administration of autologous and allogeneic NK cells after activation and expansion ex vivo is used in the treatment of cancer. Moreover, adoptive transfer of NK cell lines has been tested in humans, and genetically modified NK cells expressing chimeric antigen receptors are being studied in preclinical models for potential use in the clinic.

Cancer-associated defects in the DNA damage response: drivers for malignant transformation and potential therapeutic targets

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199495 Year: Pages: 107 DOI: 10.3389/978-2-88919-949-5 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Genetics
Added to DOAB on : 2016-01-19 14:05:46
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For this eBook, and the associated Research Topic in Frontiers in Genetics, entitled: ‘Cancer-associated defects in the DNA damage response: drivers for malignant transformation and potential therapeutic targets’ we have selected 10 papers that each discusses important, yet distinct aspects of the response to DNA damage in normal cells and cancer cells. Using an evolutionary conserved signaling network called the ‘DNA damage response (DDR)’ cells maintain the integrity of their genome, and thus safeguard cellular functioning and the ability to create viably progeny. Initially, the DDR appeared to consist of few linear kinase-driven pathways. However, research over the past decades in model organisms, as well as in the human system has revealed that the DDR is a complex signaling network, wired by multiple parallel pathways and displaying extensive crosstalk. Besides phosphorylation, multiple other post-translational modifications, including ubiquitination and sumoylation, are involved to achieve chromatin remodeling and initiation of DNA repair. Also, rather than being a cell-intrinsic phenomenon, we increasingly appreciate that cell-cell communication is involved. The recognition and repair of DNA damage is essential to maintain normal physiology. Multiple pathological conditions have been attributed to defective DNA repair, most notably accelerated aging, neurodegeneration and cancer. In the context of cancer, through repair of DNA damage or elimination of irreparably damaged cells, the DDR clearly has a tumor-suppressive role. Indeed, many tumor cells show partially inactivated DDR signaling, which allows proliferation in the context of DNA damage-inducing oncogenes. Simultaneously, loss of specific DDR signaling nodes creates a specific dependence of tumor cells on their remaining DDR components, and thus creates therapeutic opportunities. Especially in the context of cancer treatment, numerous targeted agents are under investigation, either to potentiate the cytotoxic effects of chemo-radiotherapy, or to induce synthetic lethality with cancer-specific alterations, with the treatment of BRCA1/2 mutant cancers with PARP1 inhibitors as a prototype example. We have selected four review articles that provide insight into the key components and the wiring of the DDR and DNA repair. Torgovnick and Schumacher review the involvement of DNA repair in the initiation and treatment of cancer, Brinkmann et al., describe the involvement of ubiquitination in DNA damage signaling and Jaiswal and Lindqvist discuss how cell-extrinsic signaling participates in communication of DNA damage to neighboring cells. In addition, Shatneyeva and colleagues review the connection between the cellular response to DNA damage and escape from immune surveillance. Concerning the therapeutic application of targeting the DDR and DNA repair, three articles were included. Krajewska and van Vugt review the wiring of homologous recombination and how this offers therapeutic opportunities. Additionally, Knittel and colleagues describe how genetic loss of the central DDR component ATM in chronic lymphocytic leukemia can be exploited therapeutically by targeting certain parallel DNA repair pathways. Syljuasen and colleagues report on how targeting of the DDR can be used as a therapeutic strategy in lung cancer. Finally, three chapters describe newly identified regulators of the cellular response to DNA damage. Von Morgen et al. describe the R2TP complex, Lezzi and Fanciluuli review the involvement of Che-1/AATF in the DDR, and Ohms and co-authors describe how retrotransposons are at the basis of increased genomic instability. Altogether, these articles describe how defective responses to DNA damage underlie disease - and especially in the context of cancer -can be exploited to better treat disease.

Inhibiting PARP as a Strategic Target in Cancer

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199556 Year: Pages: 97 DOI: 10.3389/978-2-88919-955-6 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Oncology
Added to DOAB on : 2016-01-19 14:05:46
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Poly-ADP ribose polymerase (PARP) proteins are critical mediators of DNA repair. Many traditional anti-cancer chemotherapy agents overwhelm a cell’s ability to repair DNA damage in order to kill proliferating malignant cells. Recent evidence suggests that cancers within and across tissue types have specific defects in DNA repair pathways, and that these defects may predispose for sensitivity and resistance to various classes of cytotoxic agents. Breast, ovarian and other cancers develop in the setting of inherited DNA repair deficiency, and these cancers may be more sensitive to cytotoxic agents that induce DNA strand breaks, as well as to inhibitors of PARP activity. A series of recent clinical trials has tested whether PARP inhibitors can achieve synthetic lethality in hereditary DNA repair-deficient tumors. At the current time, mutation of BRCA serves as a potential, but not comprehensive, biomarker to predict response to PARP inhibitor therapy. Mechanisms of resistance to PARP inhibitors are only recently being uncovered. Future studies seek to identify sporadic cancers that harbor genomic instability rendering susceptibility to PARP inhibitors that compound lethal DNA damage.

Liver Myofibroblasts

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199891 Year: Pages: 99 DOI: 10.3389/978-2-88919-989-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Physiology
Added to DOAB on : 2016-01-19 14:05:46
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Myofibroblasts (MFB) are found in most tissues of the body. They have the matrix-producing functions of fibroblasts and contractile properties that are known from smooth muscle cells. Fundamental work of the last decades has shed remarkable light on their origin, biological functions and role in disease. During hepatic injury, they fulfill manifold functions in connective tissue remodeling and wound healing, but overshooting activity of MFB on the other side induces fibrosis and cirrhosis. The present e-book "Liver myofibroblasts" contains 9 articles providing comprehensive information on "hot topics" of MFB. In our opening editorial we provide a short overview of the origin of MFB and their relevance in extracellular matrix formation which is the hallmark of hepatic fibrosis. Thereafter, leading experts in the field share their current perspectives on special topics of (i) MFB in development and disease, ii) their role in hepatic fibrogenesis, and (iii) promising therapies and targets that are suitable to interfere with hepatic fibrosis.

Cancer Nanotheranostics: What Have We Learned So Far?

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197767 Year: Pages: 128 DOI: 10.3389/978-2-88919-776-7 Language: English
Publisher: Frontiers Media SA
Subject: Chemistry (General) --- Science (General)
Added to DOAB on : 2016-04-07 11:22:02
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After a quarter of century of rapid technological advances, research has revealed the complexity of cancer, a disease intimately related to the dynamic transformation of the genome. However, the full understanding of the molecular onset of this disease is still far from achieved and the search for mechanisms of treatment will follow closely. It is here that Nanotechnology enters the fray offering a wealth of tools to diagnose and treat cancer. In fact, the National Cancer Institute predicts that over the next years, nanotechnology will result in important advances in early detection, molecular imaging, targeted and multifunctional therapeutics, prevention and control of cancer. Nanotechnology offers numerous tools to diagnose and treat cancer, such as new imaging agents, multifunctional devices capable of overcome biological barriers to deliver therapeutic agents directly to cells and tissues involved in cancer growth and metastasis, and devices capable of predicting molecular changes to prevent action against precancerous cells. Nanomaterials-based delivery systems in Theranostics (Diagnostics & Therapy) provide better penetration of therapeutic and diagnostic substances within the body at a reduced risk in comparison to conventional therapies. At the present time, there is a growing need to enhance the capability of theranostics procedures where nanomaterials-based sensors may provide for the simultaneous detection of several gene-associated conditions and nanodevices with the ability to monitor real-time drug action. These innovative multifunctional nanocarriers for cancer theranostics may allow the development of diagnostics systems such as colorimetric and immunoassays, and in therapy approaches through gene therapy, drug delivery and tumor targeting systems in cancer. Some of the thousands and thousands of published nanosystems so far will most likely revolutionize our understanding of biological mechanisms and push forward the clinical practice through their integration in future diagnostics platforms. Nevertheless, despite the significant efforts towards the use of nanomaterials in biologically relevant research, more in vivo studies are needed to assess the applicability of these materials as delivery agents. In fact, only a few went through feasible clinical trials. Nanomaterials have to serve as the norm rather than an exception in the future conventional cancer treatments. Future in vivo work will need to carefully consider the correct choice of chemical modifications to incorporate into the multifunctional nanocarriers to avoid activation off-target, side effects and toxicity. Moreover the majority of studies on nanomaterials do not consider the final application to guide the design of nanomaterial. Instead, the focus is predominantly on engineering materials with specific physical or chemical properties. It is imperative to learn how advances in nanosystem’s capabilities are being used to identify new diagnostic and therapy tools driving the development of personalized medicine in oncology; discover how integrating cancer research and nanotechnology modeling can help patient diagnosis and treatment; recognize how to translate nanotheranostics data into an actionable clinical strategy; discuss with industry leaders how nanotheranostics is evolving and what the impact is on current research efforts; and last but not least, learn what approaches are proving fruitful in turning promising clinical data into treatment realities.

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