Kidney disease is a complex health problem, often coinciding with cardiovascular pathology (e.g. hypertension) and metabolic disturbances (e.g. obesity and diabetes). It is also a disturbingly fast growing global public health problem, e.g. chronic kidney disease affects an estimated ~9-16% of the population. Besides the public health issues this results in a large economic burden as kidney diseases contributes disproportionally to about a quarter of total health care costs. Experimental and clinical data solidly support the view that kidney tissue hypoxia plays a critical and intricate role during the genesis and progression of both chronic and acute kidney diseases. This research field is currently at the very beginning of integrating pre-clinical with clinical research in which hypoxia related mechanism are quantified by non-invasive imaging. In combination with the fact that some key questions remain unanswered, this offers exciting new research perspectives that are waiting to be explored. With this Research Topic we aim to discuss and find answers to the following research question: 1) What are the temporal relationships between hypoxia and kidney disease? 2) Can we demonstration causation between hypoxia and kidney disease? 3) Can renal hypoxia be considered as a treatment target in kidney disease? 4) Can hypoxia (e.g. in the urine) be considered a biomarker of kidney disease? 5) Does hypoxia ramp-up sympathetic activity? 6) Does hypoxia trigger inflammation? 7) Is hypoxia caused by changes in sodium reabsorption and/or mitochondrial function? 8) Which molecular mechanisms are involved in hypoxia in kidney disease? 9) Which gene expressions change due to hypoxia in kidney disease? 10) Can we generate new and translational insights using non-invasive imaging technologies? Our overall aim is identify the mediators/controllers of hypoxia in kidney disease. If we understand more about the sequence of events leading to hypoxia, its regulation and consequences in renal disease, we might be able to have a major impact in clinical practice. I.e. more accurate and earlier diagnosis, novel treatment targets, and novel therapies.

Natural Bioactive Compounds: Technological Advancements deals with the latest breakthroughs in the field of screening, characterization and novel applications of natural bioactive compounds from diverse group of organisms ranging from bacteria, viruses, cyanobacteria, algae, fungi, bryophytes, higher plants, sponges, corals and fishes. Written by some of the most reputed scientists in the field, this book introduces the reader to strategies and methods in the search for bioactive natural products. It is an essential read for researchers and students interested in bioactive natural products, their biological and pharmacological properties, their possible use as chemopreventive or chemotherapeutic agents, and other future potential applications. - Explores natural sources of bioactive compounds, including cyanobacteria, bacteria, viruses, fungi and higher plants - Discusses the potential applications of biological products, such as their use in medicine (antibiotics, cancer research, immunology), as food additives, supplements and technological substances - Analyzes the contributions of emerging or developing technologies for the study of bioactive natural compounds (characterization and purification)

Due to that at present, the majority of diseases are associated with alterations in oxidative stress and inflammatory processes, and in that Nrf-2 is a modulator of these processes; knowing how this transcriptional factor functions and is regulated opens a therapeutic window to diverse diseases. Therefore, the efforts of various investigation groups are centered on finding activators and/or inhibitors of Nrf-2 to prevent or control diverse diseases, for example, cancer, where it would be important to regulate Nrf-2 in order for it to activate apoptosis pathways in cancerogenous cells, or in neurodegenerative diseases where cell death is predominant, it would be important for Nrf-2 to activate antiapoptotic pathways.

A state-of-the art collection of readily reproducible laboratory methods for assessing chemosensitivity in vitro and in vivo, and for assessing the parameters that modulate chemosensitivity in individual tumors. Chemosensitivity,Volume 2: In Vivo Models, Imaging, and Molecular Regulators contains cutting-edge protocols for classifying tumors into response categories and for customizing therapy to individuals. These readily reproducible techniques allow measurements of DNA damage, apoptotic cell death, and the molecular and cellular regulators of cytotoxicity, as well as in vivo animal modeling of chemosensitivity. A companion volume, Volume 1: In Vitro Assays contains in vitro and in vivo techniques to identify which new agents or combination of agents are effective for each type of tumor.

The book starts with the editors' preface summarizing the contributions of each of the following thirteen articles dealing with chemical and pharmacological aspects of the molecular modulators of the oxidative stress in regard to various therapeutic approaches in cardiovascular and neurodegenerative diseases, cancer, and diabetes. The seven articles present data from original research studies enlightening the roles and mechanisms of action of small molecular weight compounds (natural and synthetic; ascorbic acid/vitamin C, deferoxamine, N-acetylcysteine, MitoVitE, α-tocopherol, trolox, and ezetimibe) or proteins (SIRT3) in modulation of oxidative stress. In the six review papers, the authors present and discuss the possible therapeutic potential of novel approaches and compounds that are promising and deserve further investigation, in modulation of oxidative stress.

The past and future of inflammatory pharmacology research: a hot topic in health and disease Inflammation is a physiological response to a traumatic injury, bacterial, or viral infection. However, if not appropriately controlled, it contributes to a long list of diseases, including asthma, atherosclerosis, multiple sclerosis, arthritis, and cancer. Different are the types of inflammatory responses. Acute inflammation is an immediate body response to the cellular damage induced by pathogens, noxious stimuli, or physical injury – it is a short-term response resulting in healing via time-dependent changes of leukocyte functions. First, a leukocytes infiltration happens within the damaged region with the purpose of eliminating the stimulus and repairing the tissue. Chronic inflammation, by contrast, is a prolonged and dysregulated response where the active inflammation contributes both to tissue destruction and to the development of many chronic human conditions and diseases. In the context of exaggerated inflammation, which occurs as a consequence of severe burns or trauma, the body response called sepsis can be associated with fatal outcome. Increased knowledge of the cellular and molecular mechanisms taking part in the different types of inflammation is a central requirement to develop more effective and safer treatments. This is a necessary step to prevent potential severe consequences, i.e., organ failure associated with tissue fibrosis. The mission of Inflammation Pharmacology (section of Frontiers in Pharmacology) is to publish scientifically sound studies that advance our knowledge on different aspects of inflammation and contribute to the development of more effective and safer anti-inflammatory agents. Within the present eBook are collected the top articles published in the Inflammation Pharmacology section in the last 10 years. Some articles explored the roles played by different lipid mediators generated from arachidonic acid, including leukotrienes and prostanoids [such as prostacylin and prostaglandin(PG)F2a], in inflammatory conditions. Moreover, the protectin (PD) family of specialized pro-resolving mediators biosynthesized from the two omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and n–3 docosapentaenoic acid (n–3 DPA) were described for their biological effects, the G-coupled protein receptors pharmacology, biosynthesis, and medicinal chemistry. Some other articles focused on the development of novel strategies to counteract inflammation or to induce its resolution. The current concepts and controversies on classification, pathogenesis, and clinical management of cutaneous adverse events induced by biologic agents used in the treatment of rheumatologic conditions were discussed in another article. The whole-exome and whole-genome sequencing data identifying new and old loci associated with atherosclerosis will lead to discovering new molecular targets for blocking atherosclerosis even in its early stages. This critical issue was reviewed in another paper. Numerous information on an individual clinical condition is held in their platelet-derived microparticles (MPs); the assessment of their number and size together with their content can represent the signature to acquire diagnostic information and to monitor the efficacy of therapeutic agents. Some other articles discussed the role of fibroblasts in the development of fibrosis and potential therapies under investigation. It was enlightened the role of the activation and transdifferentiation of hepatic stellate cells (HSCs) into contractile, matrix-producing myofibroblasts (MFBs) as central events in hepatic fibrogenesis, and summarized the current strategies for targeted delivery of drugs to pro-fibrogenic liver cells, including the development of therapeutics specifically targeting HSCs. (Continued in eBook)

This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.

Oxidative stress is the result of an imbalance in pro-oxidant/antioxidant homeostasis that leads to the generation of toxic reactive oxygen species. Brain cells are continuously exposed to reactive oxygen species generated by oxidative metabolism, and in certain pathological conditions defense mechanisms against oxygen radicals may be weakened and/or overwhelmed. DNA is a potential target for oxidative damage, and genomic damage can contribute to neuropathogenesis. It is important therefore to identify tools for the quantitative analysis of DNA damage in models on neurological disorders. This book presents detailed information on various neurodegenerative disorders and their connection with oxidative stress. This information will provide clinicians with directions to treat these disorders with appropriate therapy and is also of vital importance for the drug industries for the design of new drugs for treatment of degenerative disorders.* Contains the latest information on the subject of neurodegenerative disorders* Reflects on various factors involved in degeneration and gives suggestions for how to tackle these problems

Methodology and applications of redox proteomics The relatively new and rapidly changing field of redox proteomics has the potential to revolutionize how we diagnose disease, assess risks, determine prognoses, and target therapeutic strategies for people with inflammatory and aging-associated diseases. This collection brings together, in one comprehensive volume, a broad array of information and insights into normal and altered physiology, molecular mechanisms of disease states, and new applications of the rapidly evolving techniques of proteomics. Written by some of the finest investigators in this area, Redox Proteomics: From Protein Modifications to Cellular Dysfunction and Diseases examines the key topics of redox proteomics and redox control of cellular function, including: * The role of oxidized proteins in various disorders * Pioneering studies on the development of redox proteomics * Analytical methodologies for identification and structural characterization of proteins affected by oxidative/nitrosative modifications * The response and regulation of protein oxidation in different cell types * The pathological implications of protein oxidation for conditions, including asthma, cardiovascular disease, diabetes, preeclampsia, and Alzheimer's disease Distinguished by its in-depth discussions, balanced methodological approach, and emphasis on medical applications and diagnosis development, Redox Proteomics is a rich resource for all professionals with an interest in proteomics, cellular physiology and its alterations in disease states, and related fields.