Recently, stem cells have been drawing increasing interest in basic and translational research that aims to understand stem cell biology and generate new therapies for various disorders. Many stem cells can be cultured in 2D relatively easily using tissue culture plastic. However, many of these cultures do not represent the natural conditions of stem cells in the body. In the body, microenvironments include numerous supporting cells and molecules. Therefore, researchers and clinicians have sought ideal stem cell preparations for basic research and clinical applications, which may be attainable through 3D culture of stem cells. The 3D cultures mimic the conditions of the natural environment of stem cells better, as cells in 3D cultures exhibit many unique and desirable characteristics that could be beneficial for therapeutic interventions. 3D stem cell cultures may employ supporting structures, such as various matrices or scaffolds, in addition to stem cells, to support complex structures. This book brings together recent research on 3D cultures of various stem cells to increase the basic understanding of stem cell culture techniques and also to highlight stem cell preparations for possible novel therapeutic applications.

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Natural products or organic compounds isolated from natural sources as primary or secondary metabolites have inspired numerous drugs. It is not an overstatement that the majority of medicines in clinics, even in the 21st century, have been derived from natural resources despite the decline of industry research into natural products due to a variety of drawbacks. Saffron crocus, considered to be the most valuable spice by weight, and its bioactive constituents, have been studied for the treatment of a wide range of pathologies, including neuropsychiatric and neurodegenerative disorders, cancer, diabetes, and even cardiovascular diseases. In this book on the chemistry, pharmacology, and therapeutic potential of Crocus sativus L. extract and its constituents, we aimed to assess new advances in the understanding of the therapeutic action of saffron and its constituents in targeting different pathologies. In this context, eight original research articles covering recent advances in the therapeutic actions of saffron and its ingredients in different diseases are reported. Two studies reporting novel methods regarding the bioanalysis of saffron extracts have been included. The collection is completed with two very interesting reviews reporting advances in the fields of schizophrenia and cancer. In conclusion, in this book, we are delighted to have received several contributions that we hope will provide new and interesting information for the scientific community on the chemistry, pharmacology, and therapeutic potential of Crocus sativus L. extract and its constituents.

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Gonorrhea is a sexually transmitted infection caused by the obligate human pathogen“Neisseria gonorrhoeae”. This Gram-negative diplococcus is highly infective due to its virulence factors: pili, Por proteins, Opa proteins, Rmp proteins, lipooligosaccharides and IgA protease. Despite existing guidelines for its treatment, the incidence of the disease follows an increasing trend worldwide. This is mainly due to the appearance of antibiotic-resistant strains, inefficient diagnostic methods and poor sexual education. Without an effective vaccine available, the key priorities for the control of the disease include sexual education, contact notification, epidemiological surveillance, diagnosis and effective antibiotic treatment. This Special Issue focuses on some of these important issuesm such as the molecular mechanisms of the disease, diagnostic tests and different treatment strategies used to combat gonorrhea.

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The commonness and complexity of COPD necessitate rapid communication of significant new knowledge of the disease. This book provides a platform for sharing new notions in scientific research as well as contemporary clinical best practices. It combines noetic theoretical concepts with the ontic practical management of COPD. Epistemological concepts explored in this book include contextualization in the evaluation and treatment of COPD, as well as the latest in the basic science of airway inflammation, “omics” research, and delivery therapeutics. Practical topics addressed include early detection and alleviation of COPD exacerbation, pulmonary rehabilitation, and identifying phenotypes or treatable traits to optimize inhaled therapy.

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This collection of articles provides an overview of the current and future methods for applying a personalized medicine approach to the diagnosis, management, and treatment of autism spectrum disorder.

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Adipose tissue is a rich, ubiquitous, and easily accessible source for multipotent mesenchymal stromal/stem cells (MSCs), so-called adipose-derived stromal/stem cells (ASCs). Primary isolated ASCs are a heterogeneous preparation consisting of several subpopulations of stromal/stem and precursor cells. Donor-specific differences in ASC isolations and the lack of culture standardization hinder the comparison of results from different studies. Nevertheless, ASCs are already being used in different in vivo models and clinical trials to investigate their ability to improve tissue and organ regeneration. Many questions concerning their counterparts and biology in situ, their differentiation potential in vitro and in vivo, and the mechanisms of regeneration (paracrine effects, including regeneration-promoting factors and extracellular vesicles, differentiation, and immunomodulation) are not completely understood or remain unanswered. This Special Issue covers research articles investigating various adipose tissues as a source for ASC isolation, specific cultures methods to enhance proliferation or viability, and the differentiation capacity. Furthermore, other studies highlight aspects of various diseases, the immunosuppressive potential of ASCs and their derivates, or the in vivo tracking of transplanted ASCs. This edition is complemented by a review that summarizes the current knowledge of spheroid culture system methods and applications for mesenchymal stem cells.

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The book presents several studies reporting advances on melanoma pathogenesis, diagnosis and therapy. It represents a milestone on the state of the art, updated at 2021, and also presents the current knowledge on the future developments in melanoma field.

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This book represents one of the most up-to-date collections of articles on clinical practice and research in the field of Autism Spectrum Disorders (ASD). The scholars who contributed to this book are experts in their field, carrying out cutting edge research in prestigious institutes worldwide (e.g., Harvard Medical School, University of California, MIND Institute, King’s College, Karolinska Institute, and many others). The book addressed many topics, including (1) The COVID-19 pandemic; (2) Epidemiology and prevalence; (3) Screening and early behavioral markers; (4) Diagnostic and phenotypic profile; (5) Treatment and intervention; (6) Etiopathogenesis (biomarkers, biology, and genetic, epigenetic, and risk factors); (7) Comorbidity; (8) Adulthood; and (9) Broader Autism Phenotype (BAP). This book testifies to the complexity of performing research in the field of ASD. The published contributions underline areas of progress and ongoing challenges in which more certain data is expected in the coming years. It would be desirable that experts, clinicians, researchers, and trainees could have the opportunity to read this updated text describing the challenging heterogeneity of Autism Spectrum Disorder.

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This book represents one of the most up-to-date collections of articles on clinical practice and research in the field of Autism Spectrum Disorders (ASD). The scholars who contributed to this book are experts in their field, carrying out cutting edge research in prestigious institutes worldwide (e.g., Harvard Medical School, University of California, MIND Institute, King’s College, Karolinska Institute, and many others). The book addressed many topics, including (1) The COVID-19 pandemic; (2) Epidemiology and prevalence; (3) Screening and early behavioral markers; (4) Diagnostic and phenotypic profile; (5) Treatment and intervention; (6) Etiopathogenesis (biomarkers, biology, and genetic, epigenetic, and risk factors); (7) Comorbidity; (8) Adulthood; and (9) Broader Autism Phenotype (BAP). This book testifies to the complexity of performing research in the field of ASD. The published contributions underline areas of progress and ongoing challenges in which more certain data is expected in the coming years. It would be desirable that experts, clinicians, researchers, and trainees could have the opportunity to read this updated text describing the challenging heterogeneity of Autism Spectrum Disorder.

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Significant research efforts are currently being undertaken in the field of natural and synthetic polymers for a range of biomedical applications. (Co)polymer molecular structure, topology, self-assemblies, biodegradation, and hydrophobicity are of biomaterial importance for intrinsically biocompatible polymer systems. This book is comprised of nine chapters, published previously as original research contributions of the Special Issue focused on advances in polymeric materials for biomedical applications. The authors of these contributions are predominantly from central European countries, Italy and the United Kingdom. The content of this book will be of interest to scientists, scholars and students working in this area of knowledge, reflecting the progress in the development of advanced natural and synthetic polymer biomaterials.

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Skeletal muscles are the vastest tissue in the human body with an essential role in maintaining posture, moving, and regulating internal body temperature and metabolism. Consequently, skeletal muscle injuries or diseases can have a profound effect on one’s life. In Advances in Skeletal Muscle Health and Disease, Fabio Arturo Iannotti has assembled contributions from international experts to provide a conclusive guide to what continues to be a rapidly developing research field. After a short introductory chapter, the book continues by looking at the biochemical, genetic, and molecular elements and mechanisms underlying skeletal muscle health and disease.

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Anorexia nervosa is a common eating disorder affecting several functions of the body. Although our knowledge of the underlying mechanism has increased, therapeutic options are still limited. This Special Issue discusses several aspects of anorexia nervosa and covers a broad range of topics from the bench to the bedside.

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Antioxidants in food have a dual role; on the one hand, they preserve the quality and shelf life of food products; on the other hand, they function as an external aid, helping to defend our living cells from the threat of oxidative stress. Therefore, foods rich in antioxidants are a useful tool to reduce morbidity and prevent degenerative diseases. Consequently, research related to antioxidants is continually growing. This book brings together 21 articles regarding the latest advances in the most relevant fields of food antioxidant research; from the identification and characterization of new active components, to their molecular mechanisms and the scientific evidence of their clinical use and effectiveness.

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Although advances in therapeutic interventions improved outcomes, vascular occlusive diseases are still challenging not only afflicted but also attending physicians, requiring novel therapeutic strategies. Arteriogenesis, sometimes also called therapeutic angiogenesis, refers to the body’s own capacity to create a natural bypass around a narrowing or occluded arterial vessel. This book gives an insight into current knowledge and advances in vascular sciences and future prospects of therapeutic options. The utility and relevance of circulating biomarkers together with the potential of machine learning methods are discussed as well as the challenges and prospects of novel therapies such as protein- gene-, and stem cell therapy along with multicistronic multigene vectors and the use of microRNAs, exosomes, and secretomes. Vascular smooth muscle phenotype switch as a target to promote arteriogenesis is critically addressed, highlighting the problem of promoting atherosclerosis in parallel. Two articles even deal with cold-inducible RNA-binding protein CIRP/CIRPB presenting it as promising target to promote vascularization concomitant the reduction in ischemic tissue damage. BMPR kinase inhibition is introduced to improve tissue repair in a hereditary form of vascular disorder, and the role of the AP-1 transcription factor JunB in blood vessel formation is described. Some more experimental oriented articles deal with the relevance of choosing the appropriate mouse strain for investigations as well as in vitro Matrigel plug assay as a potent method to investigate angiogenesis. Last but not least, two-photon intravital microscopy is presented as suitable tool to assess plaque angiogenesis in atherosclerotic lesions.

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In recent years, great attention has been paid to polyphenols due to their positive effects on health. One of the most widely-studied phenolic compounds is resveratrol. This molecule, which is naturally present in some foods, shows beneficial effects on various physiological and biochemical processes, thus representing a potential tool for the prevention or the treatment of diseases highly prevalent in our society. Several of these beneficial effects have been observed in human beings, but others only in pre-clinical studies so far, and therefore, it is mandatory to continue with the scientific research in this field. Indeed, new knowledge concerning these issues could enable the development of novel functional foods or nutraceuticals, incorporating resveratrol, suitable for preventing or treating diseases such as cancer, cardiovascular diseases, obesity, dislipemia, insulin resistance and diabetes, liver diseases, etc.

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Neuroimmunology is a rapidly growing emerging field at which two old sciences have converged to integrate two different types of responses into a single coherent response involving the coordinated action of both systems, neural and immune. During long time it was thought that both systems worked separately and in divergent pathways. The brain was considered an immunoprivileged site and the immune organs were deemed as independent of any neural influence and also of nervous innervation. Time has gone and has proven that the borders between both systems were merely artificial. Since the beginning of Neuroimmunology in the 1980s much work has been done to elucidate the gates and fences in neuro-immune interactions. Brain was shown to be under the continuous surveillance of the immune system, even under basal physiological conditions in the absence of any pathology. Likely, it was found a profuse nervous innervation of lymphoid organs and even of single immune cells. Gates for direct neural immune communication were found both centrally and peripherally. Centrally, the gates, but also the fences, were situated at the brain barriers, the blood-brain barrier and the blood-cerebrospinal fluid barrier, and at the circunventricular organs. Peripherally, the fences constituted the apparent diverse nature of molecules involved in neural and immune signaling; however, time proved that both system were capable of producing the same signaling molecules and also systematically responded to the molecules released by the other system. Therefore, the gates were open for direct neural-immune communication at the peripheral level. This Research Topic aimed to include original reports, reviews and technical reports regarding the description of the gates and fences in neural immune interactions. We intended to provide an extensive view of the mechanisms governing central and peripheral neural-immune interactions, and the role of the borders, the blood-neural barriers, in the regulation of the neural-immune communication.

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Increasing evidence supports the notion that bone marrow (BM) represents a relevant player in T cell responses, particularly in its role as a specialized organ for long-term memory. Memory T cells are enriched in the BM over long times after priming, and can be recruited to the periphery upon antigenic challenge. The articles in this research topic include discussions of whether these T cells are passing-through or truly resident, as well as a debate on the extent of proliferation of BM memory T cells. Original research articles in this collection include an analysis of the number of memory T cells found in different bones as well as effects of B cell depletion on T cell memory in the BM. T cells in the BM can influence a number of processes, from bone remodeling, control of cancer, to effects on hemopoiesis or Graft versus Host Disease (GVHD). This research topic contains several contributions to these topics including discussions on how to translate BM T cell knowledge into medicine.

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Liquid biopsy shows promise for cancer screening and diagnostics. This reprint collects recent scientific literature on the identification and application of tumor biomarkers in biological fluids to improve the diagnosis of cancer and the identification of optimal therapeutic strategies.

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CD4+ T lymphocytes play an essential role in host defense against bacterial, parasitic and viral infections. During infection, under the influence of intrinsic signals received through peptide-MHC/TCR interactions and extrinsic signals provided by pathogen-conditioned dendritic and other accessory cells, CD4+ T cells proliferate and differentiate into specialized T helper (Th) effectors, which produce distinct sets of cytokines tailored to combat a specific class of microbes. The concept of CD4+ T cell multi-functionality was developed after the seminal discovery of Th1 and Th2 cells nearly 30 years ago. Although the Th1/Th2 paradigm has successfully withstood the test of time, in the past decade additional Th subsets (Th17, Tfh, Th22, Th9) have been identified. Similarly, single cell analyses of cytokines and master transcriptional factors have revealed that, at the population level, CD4+ T cell responses are far more heterogeneous than initially anticipated. While some of the checkpoints in Th cell specification have been identified, recent studies of transcriptional and epigenetic regulation have uncovered a significant flexibility during the course CD4+ T lymphocyte polarization. In addition, Th cells expressing cytokines with counteracting functions, as a measure of self-regulation, display yet another level of diversity. Understanding the mechanisms that control the balance between stability vs. plasticity of Th effectors both at the time of initiation of immune response and during development of CD4 T cell memory is critical for the rational design of better vaccines and new immunotherapeutic strategies. This research topic will cover current views on Th cell development, with a focus on the mechanisms that govern differentiation, function and regulation of effector Th cells in the context of microbial infections.

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This is collection of original and review articles selected in recognition of the contribution of Instituto Butantan to the field of toxinology and its continued and relevant role in this field in the 120 years since its foundation. Congratulations to the Butantan Institute, its house scientists, and collaborators on its 120th anniversary!

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We are delighted to present this Special Issue to celebrate a remarkable milestone in the journey of Applied Dentistry. With great pleasure, we announce the publication of the journal's 20,000th paper. This remarkable achievement reflects the unwavering commitment and dedication of our esteemed authors, reviewers, and readers who have contributed to the advancement of dental research.Over the years, Applied Dentistry has emerged as a beacon of knowledge, serving as a platform for the dissemination of cutting-edge research and innovative ideas in various domains of dental science. Our journal encompasses a wide range of disciplines, covering everything from dental materials and biomaterials to preventive and therapeutic strategies, from clinical applications to regenerative dentistry.We envision this milestone as a stepping stone toward even greater accomplishments. Through the collaboration and collective efforts of researchers worldwide, we strive to push the boundaries of dental science, explore new frontiers, and improve oral health outcomes for individuals across the globe.In conclusion, we extend our warmest congratulations to all those who have contributed to the publication of the Special Issue celebrating Applied Dentistry's 20,000th paper milestone.

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Neurogenerative diseases encompass very different pathologies, which can be demyelinating or nondemyelinating, but which have common mechanisms such as cell death, oxidative stress and inflammation. A better understanding of these mechanisms allows the search for biomarkers and targets for new therapies. This special issue brings together different data on Alzheimer's disease, Parkinson's disease, and multiple sclerosis, detailing the mechanisms of cell death (necroptosis, ferroptosis), oxidative stress and inflammation but also the possibilities of neuroprotection via 5 research articles and 6 review articles. The different reviews allow us to take stock of cell death, oxidative stress and neuroinflammation in the context of neurodegenerative diseases but also in relation to other pathologies where these processes are involved.

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Materials science and engineering are strongly developing tools with increasing impact in the biotechnological and biomedical areas. Interestingly, research in molecular and cellular biology is often at the core of the design and development of materials-based approaches, providing biological rationale. Focused on research relying on biology–materials interaction, IJMS launched a Special Issue named “Cells and Materials for Disease Modeling and Regenerative Medicine”. The aim of the Special Issue was to generate a compilation of in vitro and in vivo strategies based on cell–material interactions. This book compiles the papers published in that Special Issue and includes a selection of six original scientific experimental articles and six comprehensive reviews. We are convinced that this collection of articles shows representative examples of the state of the art in the field, unveiling the relevance of materials research in generating new regenerative medicine and disease modeling approaches.

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This book provides an overview of some of the latest developments in the medical sciences, with particular emphasis on the experimental and theoretical aspects of modern medicine. In recent years, researchers working in applied health sciences have been able to identify diseases indicated by chemokines. Among the topics discussed in this book are chemokines affecting platelet functions, cytokine levels, and oxidative stress parameters in COVID-19, chemokines at the intersection of diabetes-tuberculosis synergy, chemokines in periodontal diseases, pathogenic links between hepato-digestive disorders and periodontal conditions, and IL-inflammatory carcinogenesis. Other areas included are the role of 23 receptor gene variations, the relationship between interleukin‑5 Receptor polymorphism, and immunological parameters in children with asthma. The book’s primary target audience includes students, researchers, medical practitioners, dentists, pharmacologists, and professionals interested in related fields. The book has been written by expert international scientists active in research in the health and applied sciences. We hope it will increase scientists’ knowledge of the complexity of some medical approaches, and encourage both professionals and students to devote part of their future research to understanding the mechanisms and applications of chemokines.

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This reprint is a compilation of the articles and reviews published in the Special issue entitled "Controversies and Recent Advances in Senescence and Aging" in Cells. The Editorial summarises and highlights the contents of the published articles. Aging is the leading predictive factor of many chronic diseases that account for most of the morbidity and mortality worldwide, i.e., neurodegeneration, cardiovascular, pulmonary, renal, and bone diseases, as well as cancers. Oxidative stress and reactive oxygen species generation, the over-production of inflammatory cytokines, the activation of oncogenes, DNA damage, telomere shortening, and the accumulation of senescent cells are all widely accepted mechanisms contributing to aging. Senescence is mainly thought to be provoked by negative cellular stress but might also be induced by physiological developmental stimuli. Senescence is characterized by irreversible cell cycle arrest independent of quiescence and terminal differentiation. The Special Issue entitled “Controversies and Recent Advances in Senescence and Aging”, which is contained in this reprint, comprises an excellent collection of original articles and reviews highlighting different novel aspects in the fields of senescence and aging research. They will hopefully stimulate discussions and further research in these fields, which are extremely important in a constantly aging human population.

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COVID-19 is the most prominent and rapidly evolving public health concern in the world currently. The gastrointestinal manifestations of COVID-19 are increasingly being recognized. SARS-CoV-2 infection has been associated with the occurrence of nausea, vomiting, and diarrhea. SARS-CoV-2 has also been causing pancreatic and hepatic injury. Emerging data have shown that COVID-19 patients continue to shed the virus into their stools, even when patients test negative for COVID-19 in pulmonary secretions. However, the epidemiology, pathogenesis, and treatment of SARS-CoV-2-related gastrointestinal manifestations are poorly understood. The pandemic has also had a significant impact on gastroenterologists, endoscopists, and other ancillary staff. Moreover, in the past, systematic respiratory virus syndrome (SARS) was shown to be transmitted by endoscopes, which is a big concern with COVID-19, as it shares many pathological features with SARS. The deferral of elective endoscopic procedures has negatively affected gastroenterologists. This Special Issue focuses on the current situation of this pandemic. It aims to provide insight into the gastrointestinal manifestations of COVID-19 and its effects on endoscopic procedures. I believe that this issue will be beneficial not only for gastroenterologists but also other healthcare workers around the world to recognize the often-ignored clinical gastrointestinal manifestations of COVID-19.

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Even though knowledge about the impact of the pandemic on mental health is still very limited in all countries and is largely based on experiences only partially comparable to the current epidemic, such as those of the SARS or Ebola epidemics, it is likely that the need for intervention will increase significantly in the coming months and years. Scientific research in neuroscience is a growing field. It offers a novel perspective on the relationship between mind and brain and provides novel scenarios for understanding the long wave of the current pandemic. Furthermore, the pandemic has also led to the possibility of implementing remote monitoring and management interventions. This volume uses multidisciplinary approaches to physiological and cognitive mechanisms, medical treatment, psychosocial interventions, and self-management to help illustrate the complex association among the COVID-19 pandemic, neurological manifestations, mental health, and society.

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