Dr. Kuo is the Head of Global Business Development at Predicine. The other Topic Editor declares no competing interest with regards to the Research Topic theme.

The Charnolosome as a Novel Nanothereranostic Biomarker: Overcoming Future Challenges in Medicine provides an overview of the charnolosome and its potential as a biomarker of cell injury. Based on the author's original discovery of the charnoly body in the developing, undernourished rat cerebellar Purkinje neurons, this book delves into the potential for utilizing this mitochondria and lysosomal-derived intracellular organelle as a nanotheranostic biomarker to prevent and cure various diseases. The book discusses the cellular, molecular, genetic, and epigenetic mechanisms of charnolosomes and charnolosome-derived nano-vesicles. It also investigates the molecular mechanisms underlying auto-inflammatory, autoimmune, and infectious diseases resulting from their compromised mitochondrial bioenergetics, and the potential use of the charnolosome in preventing and curing such conditions. - Shares the latest knowledge on the charnolosome and charnolosome-derived nano-vesicles and their significance at a cellular and molecular level - Considers the charnolosome in relation to a range of conditions, including neurodegenerative, metabolic, and multi-drug resistant systemic diseases - Presents future perspectives of the charnolosome in personalized nanotheranostics

As our understanding of immune mediated chronic inflammatory diseases (IMIDs) grows, it becomes more and more clear that these conditions result from the convergence of a multitude of pathogenic mechanisms whose relative individual contribution is different in different patient subsets. Promising new technologies have been conceived that address the hypotheses that targeting multiple pathways simultaneously, selectively delivering therapeutics to areas of inflammation and/or resetting the immune system, could take efficacy to new levels. However, we have long waited for the arrival of some of these technologies to the bedside, or even far enough in the drug development process in spite of the initial enthusiasm. Some of the examples covered in this book include bispecific antibodies and genomic medicines, microparticles and targeted delivery of drugs to inflamed vasculature. Most published reviews and book chapters on novel therapies for inflammatory diseases describe positive attributes of molecules or technologies under investigation and the rationale for developing them into therapeutics. The originality and potential value of this book is not in the description of these targets or technologies from the point of view of their structure or mechanism of action exclusively, but rather, in making an effort to critically address the question of what is needed to move these technologies into the clinic. Has the technology not made it past the preclinical stage and why? Has it already been tested in humans and failed? What are the potential reasons behind those failures? What do experts in each field believe can be done better to increase the probabilities of success? In addition, the authors address the competitive landscape and summarize clinical studies that have failed in the respective area. They talk about the patient populations that would be required for the successful conduction of a clinical trial to test certain molecules, and they proactively share their views regarding both the potential and the drawbacks of targets or methodologies.

The core of this three-volume book deals with damage-associated molecular patterns abbreviated “DAMPs”, which are unique molecules that save life and fight for survival of all organisms on this planet by triggering robust inflammatory/immune defense responses upon any injury, including those caused by pathogens such as viruses and bacteria. However, these molecules also have a dark side: when produced in excess upon severe insults, they can trigger serious human diseases. The three volumes present current understanding of the importance of DAMP-promoted immune responses in the etiopathogenesis of human diseases and explore how this understanding is impacting diagnosis, prognosis, and future treatment. This third volume addresses the potential of DAMPs in clinical practice, as therapeutic targets and therapeutics, by focusing on a description of antigen-related diseases, which are pathogenetically dominated by DAMPs, that is, infectious and autoimmune disorders and allograft rejection (as an undesired function of these molecules), as well as tumor rejection (as the desired function of these molecules). The book is written for professionals from all medical and paramedical disciplines who are interested in the introduction of innovative data from modern inflammation and immunity research into clinical practice. In this sense, the book reflects an approach to translational medicine. The readership will include all practitioners and clinicians, in particular, ICU clinicians, infectiologists, microbiologists, virologists, hematologists, rheumatologists, diabetologists, neurologists, transplantologists, oncologists, and pharmacists. Also available: Damage-Associated Molecular Patterns in Human Diseases - Vol. 1: Injury-Induced Innate Immune Responses; Damage-Associated Molecular Patterns in Human Diseases - Vol. 2: Danger Signals as Diagnostics, Prognostics, and Therapeutic Targets.

Remarkable advances have been made in the pathogenesis of autoimmunity, such as with bone marrow transplantation, which is becoming a powerful strategy in treating certain life-threatening diseases. The Molecular Pathology of Autoimmune Diseases is a concise and centralized resource for information on the topic, with a special focus on the molecular and genetic basis of these disorders. Dozens of international experts devote themselves to illuminating the reader in this volume, with discussions on the basic aspects of autoimmune processes to systemic and organ-specific diseases. This volume is an invaluable reference to students and professionals in immunology and related fields.

Heat shock proteins (HSPs) were discovered as polypeptides induced by stress that can be found in all kingdoms of cellular organisms. Their functions were, a first enigmatic and these proteins were thus classified by molecular weight, as in—Hsp27, Hsp70, Hsp90, Hsp110. More recently, each of these size-classified molecules has attributed a role in protein folding, and they thus came to be known, as a class, as molecular chaperones. However, the they possess properties beyond chaperoning. Indeed, their discovery in the extracellular spaces suggested roles in regulation of the immune responses.

NETosis is a unique form of cell death that is characterized by the release of decondensed chromatin and granular contents to the extracellular space. The initial observation of NETosis placed the process within the context of the innate immune response to infections. Neutrophils, the most numerous leukocytes that arrive quickly at the site of an infection, were the first cell type shown to undergo extracellular trap formation. However, subsequent studies showed that other granulocytes are also capable of releasing nuclear chromatin following stimulation. The extracellular chromatin acts to immobilize microbes and prevent their dispersal in the host. Bacterial breakdown products and inflammatory stimuli induce NETosis and the release of NETs requires enzyme activities. Histones in NET chromatin become modified by peptidylarginine deiminase 4 (PAD4) and cleaved at specific sites by proteases. NETs serve for attachment of bactericidal enzymes including myeloperoxidase, leukocyte proteases, and the cathelicidin LL-37. While the benefit of NETs in an infection appears clear, NETs also figure prominently at the center of various pathologic states. Therefore, it is important for NETs to be efficiently cleared; else digestive enzymes may gain access to tissues where inflammation takes place. Persistent NET exposure at sites of inflammation may lead to a further complication: NET antigens may provoke acquired immune responses and, over time, could initiate autoimmune reactions. Recent studies identified aberrant NET synthesis and/or clearance in inflammatory/autoimmune conditions such as systemic lupus erythematosus (SLE), psoriasis, ANCA-positive vasculitis, gout and Felty’s syndrome. In the case of SLE, for example, it appears that LL-37 exposed in the NETs may be a significant trigger of type I Interferon responses in this disease. Recent evidence also implicates aberrant NET formation in the development of endothelial damage, atherosclerosis and thrombosis. NETosis is thus of interest to researchers who investigate innate immune responses, host-pathogen interactions, chronic inflammatory disorders, cell and vascular biology, biochemistry, and autoimmunity. As we approach the 10-year-anniversary of the initial discovery of NETosis, it is useful and timely to review the so far identified mechanisms and pathways of NET formation, their role in bacterial and fungal defense and their putative importance as inducers of autoimmune responses. We look forward to a rich and rigorous discussion of these and related issues that benefit from interdisciplinary approaches, collaborations and exciting discoveries.