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Elucidating the function of mycorrhizal-induced Kunitz protease inhibitors and characterization of their putative target proteases in Medicago truncatula

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ISBN: 9783731501756 Year: Pages: XVI, 169 p. DOI: 10.5445/KSP/1000038422 Language: ENGLISH
Publisher: KIT Scientific Publishing
Subject: Biology
Added to DOAB on : 2019-07-30 20:02:02
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Most terrestrial plants live in symbiosis with arbuscular mycorrhizal fungi. In this study, a mycorrhizal-induced gene family of Medicago truncatula encoding putative Kunitz protease inhibitors was functionally characterized by means of biomolecular, biochemical, microscopical and in silico methods. Their putative target proteases were identified among a clan of serine carboxypeptidases. Results suggest that both protein families work functionally together to control mycorrhizal establishment.

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.

Second Line Treatment of Non-Small Cell Lung Cancer: Clinical; Pathological and Molecular Aspects of Novel Promising Drugs

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452637 Year: Pages: 84 DOI: 10.3389/978-2-88945-263-7 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General)
Added to DOAB on : 2018-02-27 16:16:44
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Lung cancer still remains a challenging disease with a higher mortality rate in comparison to other cancers. The discovery of oncogene addicted tumours and targeted therapies responsive to these targets lead to a meaningful change in the prognosis of these diseases. Unfortunately, these newer therapeutic options are reserved to a minor part of lung cancer patients harbouring specific mutations. In the so called wild type population, the first line options bring the median overall survival to go beyond 1 year, and in the population receiving the maintenance therapy over 16 months. Given these results, more than 60% of patients may receive a second line therapy with further opportunities to improve the length and quality of life. For patients not harbouring targetable DNA mutations newer options will be available for second line therapeutic schemes and two major assets seem to be promising: immune modulation and anti-angiogenetic agents. In particular, anti PD1/PDL1 antibodies, VEGFR antibodies and TKIs, these latter combined with standard chemotherapy docetaxel advance the median overall survival of 12 months. These drugs have a different mechanism of action, various adverse events and their activity is different depending on the types of population. However, the biomarkers’ activity and efficacy prediction are not fully or totally understood. In addition, also for patients with DNA targetable mutations new drugs seems to be promising for the use in the second line therapeutic protocols. In particular, drugs selectively directed against ALK translocation and mutational events and EGFR T790M secondary mutations seems to be very promising. In this Research Topic we critically discuss the older therapies and the historical development of second line, putting in to perspective the new agents available in clinical practice. We discuss their importance from a clinical point of view, but also consider and exploit the complex molecular mechanisms responsible of their efficacy or of the subsequently observed resistance phenomena. In this perspective, the undercovering and characterization of novel predictive biomarkers by NGS technology, the characterization of novel actors in the signal transduction pathway modulating the response of the cells, the optimization of new diagnostic tool as the evaluation of liquid biopsy and the implementation of more suitable pre-clinical models are crucial aspects dissected too. Nivolumab, nintedanib and ramucirumab probably will give the opportunity to improve the efficacy outcomes for the treatment of wild type tumours in second line therapeutic schemes, but many aspects should be debated in order that these agents are made available to patients, planning ahead a therapeutic strategy, beginning from the first line therapy, to the subsequent ones in a logical and affordable manner. As well, for treatment of mutated tumours, mutated EGFR irreversible inhibitors such as rociletinib and AZD9291, and ALK targeting drugs ceritinib and alectinib will also play an important role in the immediate future. Probably the right way is to give all the available opportunities to patients, but challenges and pitfalls should be carefully debated, and by launching this Research Topic we tried to give some practical insights in this changing landscape.

MERS-CoV

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ISBN: 9783039218509 / 9783039218516 Year: Pages: 274 DOI: 10.3390/books978-3-03921-851-6 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2020-01-07 09:08:26
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Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging zoonotic coronavirus. First identified in 2012, MERS-CoV has caused over 2460 infections and a fatality rate of about 35% in humans. Similar to severe acute respiratory syndrome coronavirus (SARS-CoV), MERS-CoV likely originated from bats; however, different from SARS-CoV, which potentially utilized palm civets as its intermediate hosts, MERS-CoV likely transmits to humans through dromedary camels. Animal models, such as humanized mice and nonhuman primates, have been developed for studying MERS-CoV infection. Currently, there are no vaccines and therapeutics approved for the prevention and treatment of MERS-CoV infection, although a number of them have been developed preclinically or tested clinically. This book covers one editorial and 16 articles (including seven review articles and nine original research papers) written by researchers working in the field of MERS-CoV. It describes the following three main aspects: (1) MERS-CoV epidemiology, transmission, and pathogenesis; (2) current progress on MERS-CoV animal models, vaccines, and therapeutics; and (3) challenges and future prospects for MERS-CoV research. Overall, this book will help researchers in the MERS-CoV field to further advance their work on the virus. It also has important implications for other coronaviruses as well as viruses outside the coronavirus family with pandemic potentials.

Staphylococcus aureus Toxins

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ISBN: 9783039214259 / 9783039214266 Year: Pages: 204 DOI: 10.3390/books978-3-03921-426-6 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Microbiology
Added to DOAB on : 2019-12-09 11:49:15
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Staphylococcus aureus is a common inhabitant of the human body with which we co-exist. However, this species can also cause disease in humans when an appropriate opportunity arises, such as a cut or some other breakdown in our body’s defenses. S. aureus is able to initiate infections due, in part, to the diverse group of toxins that they secrete. The exotoxins produced by S. aureus can cause direct damage, thwart our own body’s defenses, or trigger massive amounts of cytokines that lead to indirect damage within the human body. In this book are 12 research articles that deal with different aspects of staphylococcal exotoxins. Some of the work gives an overview about how the toxins contribute to the disease process. Other articles discuss different aspects of several exotoxins, and two articles are centered on countermeasures against S. aureus infections. Overall, this book will give the reader a good overview of how staphylococcal exotoxins contribute to initiating and sustaining infections in humans.

Anticancer Drugs

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ISBN: 9783039215867 / 9783039215874 Year: Pages: 214 DOI: 10.3390/books978-3-03921-587-4 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Chemistry (General)
Added to DOAB on : 2019-12-09 11:49:15
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The past decades have seen major developments in the understanding of the cellular and molecular biology of cancer. Significant progress has been achieved regarding long-term survival for the patients of many cancers with the use of tamoxifen for treatment of breast cancer, treatment of chronic myeloid leukaemia with imatinib, and the success of biological drugs. The transition from cytotoxic chemotherapy to targeted cancer drug discovery and development has resulted in an increasing selection of tools available to oncologists. In this Special Issue of Pharmaceuticals, we highlight the opportunities and challenges in the discovery and design of innovative cancer therapies, novel small-molecule cancer drugs and antibody–drug conjugates, with articles covering a variety of anticancer therapies and potential relevant disease states and applications. Significant efforts are being made to develop and improve cancer treatments and to translate basic research findings into clinical use, resulting in improvements in survival rates and quality of life for cancer patients. We demonstrate the possibilities and scope for future research in these areas and also highlight the challenges faced by scientists in the area of anticancer drug development leading to improved targeted treatments and better survival rates for cancer patients.

Genome Mining and Marine Microbial Natural Products

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ISBN: 9783039280902 / 9783039280919 Year: Pages: 202 DOI: 10.3390/books978-3-03928-091-9 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Microbiology --- Biology --- Science (General)
Added to DOAB on : 2020-01-30 16:39:46
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Two review papers, eight research articles, and one brief report were published in this Special Issue. They showed the rich resources that are present within the genomes of marine microorganisms and discussed the use of recently developed tools and technologies to exploit this genetic richness. Examples include the rational supply of precursors according to the relevant biosynthetic pathway and stress driven discovery together with the use of histone deacetylase inhibitors to facilitate the discovery of new bioactive molecules with potential biopharmaceutical applications. We believe that the content of this Special Issue reflects the current state-of-the-art research in this area and highlights the interesting strategies that are being employed to uncover increasing numbers of exciting novel compounds for drug discovery from marine genetic resources.

mTOR in Human Diseases

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ISBN: 9783039210602 / 9783039210619 Year: Pages: 480 DOI: 10.3390/books978-3-03921-061-9 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General)
Added to DOAB on : 2019-06-26 08:44:06
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The mechanistic target of rapamycin (mTOR) is a major signaling intermediary that coordinates favorable environmental conditions with cell growth. Indeed, as part of two functionally distinct protein complexes, named mTORC1 and mTORC2, mTOR regulates a variety of cellular processes, including protein, lipid, and nucleotide synthesis, as well as autophagy. Over the last two decades, major molecular advances have been made in mTOR signaling and have revealed the complexity of the events implicated in mTOR function and regulation. In parallel, the role of mTOR in diverse pathological conditions has also been identified, including in cancer, hamartoma, neurological, and metabolic diseases. Through a series of articles, this book focuses on the role played by mTOR in cellular processes, metabolism in particular, and highlights a panel of human diseases for which mTOR inhibition provides or might provide benefits. It also addresses future studies needed to further characterize the role of mTOR in selected disorders, which will help design novel therapeutic approaches. It is therefore intended for everyone who has an interest in mTOR biology and its application in human pathologies.

Keywords

acute myeloid leukemia --- metabolism --- mTOR --- PI3K --- phosphorylation --- epithelial to mesenchymal transition --- mTOR inhibitor --- pulmonary fibrosis --- transcriptomics --- miRNome --- everolimus --- mTOR --- thyroid cancer --- sodium iodide symporter (NIS)/SLC5A5 --- dopamine receptor --- autophagy --- AKT --- mTOR --- AMPK --- mTOR --- Medulloblastoma --- MBSCs --- mTOR --- T-cell acute lymphoblastic leukemia --- targeted therapy --- combination therapy --- mTOR --- metabolic diseases --- glucose and lipid metabolism --- anesthesia --- neurotoxicity --- synapse --- mTOR --- neurodevelopment --- mTOR --- rapamycin --- autophagy --- protein aggregation --- methamphetamine --- schizophrenia --- tumour cachexia --- mTOR --- signalling --- metabolism --- proteolysis --- lipolysis --- mTOR --- mTORC1 --- mTORC2 --- rapamycin --- rapalogues --- rapalogs --- mTOR inhibitors --- senescence --- ageing --- aging --- cancer --- neurodegeneration --- immunosenescence --- senolytics --- biomarkers --- leukemia --- cell signaling --- metabolism --- apoptosis --- miRNA --- mTOR inhibitors --- mTOR --- tumor microenvironment --- angiogenesis --- immunotherapy --- fluid shear stress --- melatonin --- chloral hydrate --- nocodazole --- MC3T3-E1 cells --- primary cilia --- mTOR complex --- metabolic reprogramming --- cancer --- microenvironment --- nutrient sensor --- oral cavity squamous cell carcinoma (OSCC) --- NVP-BEZ235 --- mTOR --- p70S6K --- mTOR --- advanced biliary tract cancers --- mTOR --- NGS --- illumina --- IonTorrent --- eIFs --- mTOR --- autophagy --- Parkinson’s disease --- mTOR --- PI3K --- cancer --- inhibitor --- therapy --- mTOR --- laminopathies --- lamin A/C --- Emery-Dreifuss muscular dystrophy (EDMD) --- Hutchinson-Gilford progeria syndrome (HGPS) --- autophagy --- cellular signaling --- metabolism --- bone remodeling --- ageing --- mTOR --- fructose --- glucose --- liver --- lipid metabolism --- gluconeogenesis --- Alzheimer’s disease --- autophagy --- mTOR signal pathway --- physical activity --- microRNA --- mTOR --- spermatogenesis --- male fertility --- Sertoli cells --- n/a

Polyamine Metabolism in Disease and Polyamine-Targeted Therapies

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ISBN: 9783039211524 / 9783039211531 Year: Pages: 240 DOI: 10.3390/books978-3-03921-153-1 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 11:49:15
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Polyamines are ubiquitous polycations essential for all cellular life. The most common polyamines in eukaryotes, spermine, spermidine, and putrescine, exist in millimolar intracellular concentrations that are tightly regulated through biosynthesis, catabolism, and transport. Polyamines interact with, and regulate, negatively charged macromolecules, including nucleic acids, proteins, and ion channels. Accordingly, alterations in polyamine metabolism affect cellular proliferation and survival through changes in gene expression and transcription, translation, autophagy, oxidative stress, and apoptosis. Dysregulation of these multifaceted polyamine functions contribute to multiple disease processes, thus their metabolism and function have been targeted for preventive or therapeutic intervention. The correlation between elevated polyamine levels and cancer is well established, and ornithine decarboxylase, the rate-limiting biosynthetic enzyme in the production of putrescine, is a bona fide transcriptional target of the Myc oncogene. Furthermore, induced polyamine catabolism contributes to carcinogenesis that is associated with certain forms of chronic infection and/or inflammation through the production of reactive oxygen species. These and other characteristics specific to cancer cells have led to the development of polyamine-based agents and inhibitors aimed at exploiting the polyamine metabolic pathway for chemotherapeutic and chemopreventive benefit. In addition to cancer, polyamines are involved in the pathologies of neurodegenerative diseases including Alzheimer’s and Parkinson’s, parasitic and infectious diseases, wound healing, ischemia/reperfusion injuries, and certain age-related conditions, as polyamines are known to decrease with age. As in cancer, polyamine-based therapies for these conditions are an area of active investigation. With recent advances in immunotherapy, interest has increased regarding polyamine-associated modulation of immune responses, as well as potential immunoregulation of polyamine metabolism, the results of which could have relevance to multiple disease processes. The goal of this Special Issue of Medical Sciences is to present the most recent advances in polyamine research as it relates to health, disease, and/or therapy.

Keywords

polyamine transport inhibitor --- Drosophila imaginal discs --- difluoromethylorthinine --- DFMO --- polyamine --- cancer --- metabolism --- difluoromethylornithine --- polyamine transport inhibitor --- pancreatic ductal adenocarcinoma --- curcumin --- diferuloylmethane --- ornithine decarboxylase --- polyamine --- NF-?B --- chemoprevention --- carcinogenesis --- polyphenol --- ornithine decarboxylase --- polyamines --- untranslated region --- polyamines --- ?-difluoromethylornithine --- polyamine transport system --- melanoma --- mutant BRAF --- spermine --- spermidine --- putrescine --- polyamine metabolism --- mast cells --- eosinophils --- neutrophils --- M2 macrophages --- airway smooth muscle cells --- Streptococcus pneumoniae --- polyamines --- pneumococcal pneumonia --- proteomics --- capsule --- complementation --- metabolism --- cadaverine --- polyamines --- ornithine decarboxylase --- difluoromethylornithine --- eflornithine --- DFMO --- African sleeping sickness --- hirsutism --- colorectal cancer --- neuroblastoma --- aging --- atrophy --- autophagy --- oxidative stress --- polyamines --- skeletal muscle --- spermidine --- spermine oxidase --- transgenic mouse --- immunity --- T-lymphocytes --- B-lymphocytes --- tumor immunity --- metabolism --- epigenetics --- autoimmunity --- polyamines --- ornithine decarboxylase --- polyamine analogs --- spermidine/spermine N1-acetyl transferase --- spermine oxidase --- bis(ethyl)polyamine analogs --- breast cancer --- MCF-7 cells --- transgenic mice --- polyamines --- MYC --- protein synthesis in cancer --- neuroblastoma --- protein expression --- antizyme 1 --- ornithine decarboxylase --- CRISPR --- human embryonic kidney 293 (HEK293) --- cell differentiation --- DFMO --- ornithine decarboxylase --- osteosarcoma --- polyamines --- polyamines --- polyamine metabolism --- antizyme --- antizyme inhibitors --- ornithine decarboxylase --- Snyder-Robinson Syndrome --- spermine synthase --- X-linked intellectual disability --- polyamine transport --- spermidine --- spermine --- transglutaminase

Carbonic Anhydrases and Metabolism

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ISBN: 9783038978008 9783038978015 Year: Pages: 184 DOI: 10.3390/books978-3-03897-801-5 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-04-25 16:37:17
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Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes present in all kingdoms of life, as they equilibrate the reaction between three simple but essential chemical species: CO2, bicarbonate, and protons. Discovered more than 80 years ago, in 1933, these enzymes have been extensively investigated due to the biomedical application of their inhibitors, but also because they are an extraordinary example of convergent evolution, with seven genetically distinct CA families that evolved independently in Bacteria, Archaea, and Eukarya. CAs are also among the most efficient enzymes known in nature, due to the fact that the uncatalyzed hydration of CO2 is a very slow process and the physiological demands for its conversion to ionic, soluble species is very high. Inhibition of the CAs has pharmacological applications in many fields, such as antiglaucoma, anticonvulsant, antiobesity, and anticancer agents/diagnostic tools, but is also emerging for designing anti-infectives, i.e., antifungal, antibacterial, and antiprotozoan agents with a novel mechanism of action. Mitochondrial CAs are implicated in de novo lipogenesis, and thus selective inhibitors of such enzymes may be useful for the development of new antiobesity drugs. As tumor metabolism is diverse compared to that of normal cells, ultimately, relevant contributions on the role of the tumor-associated isoforms CA IX and XII in these phenomena have been published and the two isoforms have been validated as novel antitumor/antimetastatic drug targets, with antibodies and small-molecule inhibitors in various stages of clinical development. CAs also play a crucial role in other metabolic processes connected with urea biosynthesis, gluconeogenesis, and so on, since many carboxylation reactions catalyzed by acetyl-coenzyme A carboxylase or pyruvate carboxylase use bicarbonate, not CO2, as a substrate. In organisms other than mammals, e.g., plants, algae, and cyanobacteria, CAs are involved in photosynthesis, whereas in many parasites (fungi, protozoa), they are involved in the de novo synthesis of important metabolites (lipids, nucleic acids, etc.). The metabolic effects related to interference with CA activity, however, have been scarcely investigated. The present Special Issue of Metabolites aims to fill this gap by presenting the latest developments in the field of CAs and their role in metabolism.

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