-
International Journal of Molecular... Mar 2021Inflammation is an innate immunity protecting the body from pathogens and cellular damages and comprises two steps; 1) priming (preparatory step) and triggering...
Inflammation is an innate immunity protecting the body from pathogens and cellular damages and comprises two steps; 1) priming (preparatory step) and triggering (activation step). The key feature of the triggering step is the activation of inflammasomes that are intracellular protein complexes consisting of pattern recognition receptors and inflammatory molecules. Inflammasomes are activated in response to various ligands, leading to the caspase-1-mediated maturation and secretion of pro-inflammatory cytokines, IL-1β and IL-18 and the gasdermin D-mediated pyroptosis, an inflammatory form of cell death. Previous studies have demonstrated that inflammasome activation is a key determinant of inflammatory responses and many human diseases; therefore, inflammasomes have been attracted much attention as critical drug targets to prevent and treat various human diseases.
Topics: Animals; Biomarkers; Disease; Flavonoids; Humans; Inflammasomes; Inflammation; Mice
PubMed: 33809447
DOI: 10.3390/ijms22063008 -
Clinical Pharmacology and Therapeutics Sep 2019Metabolic disturbances have been associated with many human diseases, including cancer, diabetes, and cardiovascular disease. Metabolomics, a rapidly growing member of... (Review)
Review
Metabolic disturbances have been associated with many human diseases, including cancer, diabetes, and cardiovascular disease. Metabolomics, a rapidly growing member of the -omics family, investigates cellular metabolism by quantifying metabolites on a large scale and provides a link between metabolic pathways and the upstream genome that governs them. With the advances in analytical technologies, metabolomics is becoming a powerful tool for identifying diagnostic biomarkers of diseases, elucidating the pathological mechanisms, discovering novel drug targets, predicting drug responses, interpreting the mechanisms of drug action, as well as enabling precision treatment of patients. In this review, we highlight the recent advances of technologies and methodologies in metabolomics and their applications to the field of clinical pharmacology. Recent publications from 2013 to 2018 are covered in the review, and current challenges and potential future directions in the field are also discussed.
Topics: Biomarkers; Diagnosis, Differential; Disease; Drug Development; Humans; Mass Spectrometry; Metabolomics; Pathology; Pharmacogenetics; Pharmacokinetics; Pharmacology, Clinical; Precision Medicine; Prognosis
PubMed: 31173340
DOI: 10.1002/cpt.1538 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2019The authors present a case-report of Segawa's syndrome. Clinical characteristics, genetic background and treatment options with special emphasis on a differential...
The authors present a case-report of Segawa's syndrome. Clinical characteristics, genetic background and treatment options with special emphasis on a differential diagnosis are discussed.
Topics: Diagnosis, Differential; Dystonic Disorders; Humans; Syndrome
PubMed: 31156223
DOI: 10.17116/jnevro201911904155 -
Methods in Molecular Biology (Clifton,... 2015Mast cells are primarily known for their role in defense against pathogens, particularly bacteria; neutralization of venom toxins; and for triggering allergic responses... (Review)
Review
Mast cells are primarily known for their role in defense against pathogens, particularly bacteria; neutralization of venom toxins; and for triggering allergic responses and anaphylaxis. In addition to these direct effector functions, activated mast cells rapidly recruit other innate and adaptive immune cells and can participate in "tuning" the immune response. In this review we touch briefly on these important functions and then focus on some of the less-appreciated roles of mast cells in human disease including cancer, autoimmune inflammation, organ transplant, and fibrosis. Although it is difficult to formally assign causal roles to mast cells in human disease, we offer a general review of data that correlate the presence and activation of mast cells with exacerbated inflammation and disease progression. Conversely, in some restricted contexts, mast cells may offer protective roles. For example, the presence of mast cells in some malignant or cardiovascular diseases is associated with favorable prognosis. In these cases, specific localization of mast cells within the tissue and whether they express chymase or tryptase (or both) are diagnostically important considerations. Finally, we review experimental animal models that imply a causal role for mast cells in disease and discuss important caveats and controversies of these findings.
Topics: Animals; Disease; Health; Humans; Mast Cells; Microbiology; Transplants; Venoms
PubMed: 25388247
DOI: 10.1007/978-1-4939-1568-2_7 -
Annual Review of Cell and Developmental... Oct 2017Cells and organisms have evolved numerous mechanisms to cope with and to adapt to unexpected challenges and harsh conditions. Proteins are essential to perform the vast... (Review)
Review
Cells and organisms have evolved numerous mechanisms to cope with and to adapt to unexpected challenges and harsh conditions. Proteins are essential to perform the vast majority of cellular and organismal functions. To maintain a healthy proteome, cells rely on a network of factors and pathways collectively known as protein quality control (PQC) systems, which not only ensure that newly synthesized proteins reach a functional conformation but also are essential for surveillance, prevention, and rescue of protein defects. The main players of PQC systems are chaperones and protein degradation systems: the ubiquitin-proteasome system and autophagy. Here we provide an integrated overview of the diverse PQC systems in eukaryotic cells in health and diseases, with an emphasis on the key regulatory aspects and their cross talks. We also highlight how PQC regulation may be exploited for potential therapeutic benefit.
Topics: Amino Acids; Animals; Disease; Eukaryotic Cells; Homeostasis; Humans; Proteins; Stress, Physiological
PubMed: 28992440
DOI: 10.1146/annurev-cellbio-111315-125334 -
International Journal of Molecular... Jan 2019In all kingdoms of life, proteins are synthesized by ribosomes in a process referred to as translation. The amplitude of translational regulation exceeds the sum of... (Review)
Review
In all kingdoms of life, proteins are synthesized by ribosomes in a process referred to as translation. The amplitude of translational regulation exceeds the sum of transcription, mRNA degradation and protein degradation. Therefore, it is essential to investigate translation in a global scale. Like the other "omics"-methods, translatomics investigates the totality of the components in the translation process, including but not limited to translating mRNAs, ribosomes, tRNAs, regulatory RNAs and nascent polypeptide chains. Technical advances in recent years have brought breakthroughs in the investigation of these components at global scale, both for their composition and dynamics. These methods have been applied in a rapidly increasing number of studies to reveal multifaceted aspects of translation control. The process of translation is not restricted to the conversion of mRNA coding sequences into polypeptide chains, it also controls the composition of the proteome in a delicate and responsive way. Therefore, translatomics has extended its unique and innovative power to many fields including proteomics, cancer research, bacterial stress response, biological rhythmicity and plant biology. Rational design in translation can enhance recombinant protein production for thousands of times. This brief review summarizes the main state-of-the-art methods of translatomics, highlights recent discoveries made in this field and introduces applications of translatomics on basic biological and biomedical research.
Topics: Animals; Disease; Humans; Internet; Protein Biosynthesis; Proteomics; RNA, Messenger; Ribosomes
PubMed: 30626072
DOI: 10.3390/ijms20010212 -
Molecular Immunology Dec 2021C1q is the recognition molecule of the classical pathway of the complement system. By binding to its targets, such as antigen-bound immunoglobulins or C-reactive... (Review)
Review
C1q is the recognition molecule of the classical pathway of the complement system. By binding to its targets, such as antigen-bound immunoglobulins or C-reactive protein, C1q contributes to the innate defense against infections. However, C1q also plays several other roles beyond its traditional role in complement activation. Circulating levels of C1q are determined in routine diagnostics as biomarker in several diseases. Decreased C1q levels are present in several autoimmune conditions. The decreased levels reflect the consumption of C1q by complement activation and serves as a biomarker for disease activity. In contrast, increased C1q levels are present in infectious and inflammatory diseases and may serve as a diagnostic biomarker. The increased levels of C1q are still incompletely understood but are suggested to modulate the adaptive immune response as C1q is known to impact on the maturation status of antigen-presenting cells and C1q impacts directly on T cells leading to decreased T-cell activity in high C1q conditions. In this review, we provide a comprehensive overview of the current literature on circulating levels of C1q in health and disease, and discuss how C1q can both protect against infections as well as maintain tolerance by regulating adaptive immunity.
Topics: Adaptive Immunity; Animals; Antibodies; Biomarkers; Complement C1q; Disease; Health; Humans
PubMed: 34735869
DOI: 10.1016/j.molimm.2021.10.010 -
Trends in Cell Biology Mar 2017Extracellular vesicles (EVs) are a heterogeneous collection of membrane-bound carriers with complex cargoes including proteins, lipids, and nucleic acids. While the... (Review)
Review
Extracellular vesicles (EVs) are a heterogeneous collection of membrane-bound carriers with complex cargoes including proteins, lipids, and nucleic acids. While the release of EVs was previously thought to be only a mechanism to discard nonfunctional cellular components, increasing evidence implicates EVs as key players in intercellular and even interorganismal communication. EVs confer stability and can direct their cargoes to specific cell types. EV cargoes also appear to act in a combinatorial manner to communicate directives to other cells. This review focuses on recent findings and knowledge gaps in the area of EV biogenesis, release, and uptake. In addition, we highlight examples whereby EV cargoes control basic cellular functions, including motility and polarization, immune responses, and development, and contribute to diseases such as cancer and neurodegeneration.
Topics: Biological Transport; Disease; Extracellular Space; Extracellular Vesicles; Humans; Membrane Fusion; Models, Biological
PubMed: 27979573
DOI: 10.1016/j.tcb.2016.11.003 -
Science (New York, N.Y.) Nov 2016Biological clocks are autonomous anticipatory oscillators that play a critical role in the organization and information processing from genome to whole organisms.... (Review)
Review
Biological clocks are autonomous anticipatory oscillators that play a critical role in the organization and information processing from genome to whole organisms. Transformative advances into the clock system have opened insight into fundamental mechanisms through which clocks program energy transfer from sunlight into organic matter and potential energy, in addition to cell development and genotoxic stress response. The identification of clocks in nearly every single cell of the body raises questions as to how this gives rise to rhythmic physiology in multicellular organisms and how environmental signals entrain clocks to geophysical time. Here, we consider advances in understanding how regulatory networks emergent in clocks give rise to cell type-specific functions within tissues to affect homeostasis.
Topics: Animals; Circadian Clocks; Circadian Rhythm; Disease; Drosophila melanogaster; Gene Regulatory Networks; Homeostasis; Humans; Physical Fitness; Plants
PubMed: 27885004
DOI: 10.1126/science.aah4965 -
Advances in Experimental Medicine and... 2020Clinical single-cell biomedicine has become a new emerging discipline, which integrates single-cell RNA and DNA sequencing, proteomics, and functions with clinical... (Review)
Review
Clinical single-cell biomedicine has become a new emerging discipline, which integrates single-cell RNA and DNA sequencing, proteomics, and functions with clinical phenomes, therapeutic responses, and prognosis. It is of great value to discover disease-, phenome-, and therapy-specific diagnostic biomarkers and therapeutic targets on the basis of the principle of clinical single-cell biomedicine. This book reviews the roles of single-cell sequencing and methylation in diseases and explores disease-specific alterations of single-cell sequencing and methylation, especially focusing on potential applications of methodologies on human single-cell sequencing and methylation, on potential correlations between those changes with pulmonary diseases, and on potential roles of signaling pathways that cause heterogeneous cellular responses during treatment. This book also emphasizes the importance of methodologies in clinical practice and application, the potential of perspectives, challenges and solutions, and the significance of single-cell preparation standardization. Alterations of DNA and RNA methylation, demethylation in lung diseases, and a deep knowledge about the regulation and function of target gene methylation for diagnosing and treating diseases at the early stage are also provided. Importantly, this book aims to apply the measurement of single-cell sequencing and methylation for clinical diagnosis and treatment and to understand clinical values of those parameters and to headline and foresee the potential values of the application of single-cell sequencing in non-cancer diseases.
Topics: DNA; DNA Methylation; Disease; Humans; Proteomics; RNA; Sequence Analysis; Single-Cell Analysis
PubMed: 32949386
DOI: 10.1007/978-981-15-4494-1_1