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Current Opinion in Pharmacology Oct 2008MicroRNAs (miRNAs) are short non-coding RNAs involved in post-transcriptional regulation of gene expression. Since the discovery of the first miRNA gene lin-4 in C.... (Review)
Review
MicroRNAs (miRNAs) are short non-coding RNAs involved in post-transcriptional regulation of gene expression. Since the discovery of the first miRNA gene lin-4 in C. elegans, over 500 miRNAs have been identified in humans and the list is growing. Their biological importance, initially demonstrated in cancer, was also more recently discovered in many other pathologies like Alzheimer's disease, Parkinson's disease, viral infections, diabetes, and myopathies. In the present review we will summarize miRNA profiling studies in human diseases and discuss the newly discovered link between microRNAs and drug response. An understanding of how microRNAs influence the body's response to certain drugs and how these affect the expression of microRNAs, will be of key importance in developing drugs with greater safety and efficacy.
Topics: Animals; Disease; Humans; MicroRNAs; Neoplasms; Protein Processing, Post-Translational; RNA Processing, Post-Transcriptional
PubMed: 18619557
DOI: 10.1016/j.coph.2008.06.005 -
Archives of AIDS Research 1987
Topics: Behavior; Contraception; Disease; Family Planning Services; HIV Infections; Homosexuality; Insemination, Artificial; Intrauterine Devices; Reproduction; Reproductive Techniques; Sexual Behavior; Sperm Banks; Sperm Transport; Virus Diseases
PubMed: 12315311
DOI: No ID Found -
Journal of Leukocyte Biology Dec 1999Macrophages are ubiquitous in the stromal compartment of tissues under normal physiological conditions and the number of these cells increases markedly with the onset... (Review)
Review
Macrophages are ubiquitous in the stromal compartment of tissues under normal physiological conditions and the number of these cells increases markedly with the onset and progression of many pathological states. The mechanisms underlying this response are well described in such conditions as wound healing and malignant tumors, where tissue-specific signals enhance the extravasation of blood monocytes and their subsequent differentiation into macrophages. Recent evidence suggests that macrophages may also be stimulated by microenvironmental factors present in diseased tissues to perform distinct, tissue-specific activities. One such factor, hypoxia (low oxygen tension), results from insufficient vascular perfusion of a given tissue. Various studies have shown that experimental hypoxia alters the morphology, expression of cell surface markers, viability, phagocytosis, metabolic activity, and release of cytokines by macrophages. Here we review the evidence for these macrophage responses to hypoxia, the involvement of co-stimuli, and their implications for the role of macrophages in various disease processes. Because the intracellular mechanisms mediating the effects of hypoxia on gene expression in other cell types have been characterized recently, we discuss their possible involvement in the effects of hypoxia on gene expression in macrophages.
Topics: Animals; Cell Hypoxia; Disease; Humans; Macrophages
PubMed: 10614769
DOI: 10.1002/jlb.66.6.889 -
Blood Aug 1990Recognized manifestations of acute graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract include secretory diarrhea, abdominal pain, and, at times,...
Recognized manifestations of acute graft-versus-host disease (GVHD) of the gastrointestinal (GI) tract include secretory diarrhea, abdominal pain, and, at times, hemorrhage. In a review of 469 patients undergoing allogeneic bone marrow transplantation (BMT) from matched sibling donors at our institution, we have recognized a syndrome of upper GI GVHD. This syndrome, presenting clinically as anorexia, dyspepsia, food intolerance, nausea, and vomiting, was recognized and confirmed histologically in 62 patients (13% by Kaplan-Meier projection) at the initiation of systemic GVHD therapy, a subset of the 197 patients developing grade II through IV GVHD. These 62 patients with upper GI GVHD were significantly older than the overall BMT population and older than the cohort with grade II through IV GVHD, as well. Of the 62 patients, 25 had upper GI GVHD accompanied only by limited (stage 1 and 2) skin GVHD; 13 others with upper GI GVHD plus limited skin involvement at initial presentation later progressed to more extensive multiorgan involvement; 24 others presented with upper GI along with other organ GVHD. This upper GI GVHD syndrome, first recognized at our center in 1983, has been diagnosed with increasing frequency (22% +/- 5%) in the most recent 5-year interval. The upper GI GVHD syndrome is more responsive to immunosuppressive therapy than grade II GVHD defined by Seattle criteria, with complete and continuing responses to treatment observed in 71% +/- 17% (95% confidence interval) of those with the upper GI GVHD syndrome compared with only 37% +/- 10% complete responses in other patients with grade II GVHD (P = .002). Patients failing immunosuppressive therapy for upper GI GVHD often progress to symptomatic lower GI involvement, suggesting that this syndrome may be an earlier and perhaps more treatable manifestation of this unique intestinal immunopathology, which is followed by chronic GVHD in 74% of patients. While upper GI GVHD symptoms are nonspecific and require invasive histologic and microbiologic studies to confirm the diagnosis, we believe this syndrome has been underreported after allogeneic BMT and propose its recognition within the clinical GVHD scoring system.
Topics: Acute Disease; Adolescent; Adult; Bone Marrow Transplantation; Gastrointestinal Diseases; Graft vs Host Disease; Humans; Immunosuppression Therapy; Middle Aged; Syndrome; Transplantation, Homologous
PubMed: 2378989
DOI: No ID Found -
Seminars in Cell & Developmental Biology Jan 2020The literature about Developmental Origins of Health and Disease (DOHaD) studies is considerably growing. Maternal and paternal environment, during all the development... (Review)
Review
Epigenetics and the Developmental Origins of Health and Disease: Parental environment signalling to the epigenome, critical time windows and sculpting the adult phenotype.
The literature about Developmental Origins of Health and Disease (DOHaD) studies is considerably growing. Maternal and paternal environment, during all the development of the individual from gametogenesis to weaning and beyond, as well as the psychosocial environment in childhood and teenage, can shape the adult and the elderly person's susceptibility to her/his own environment and diseases. This non-conventional, non-genetic, inheritance is underlain by several mechanisms among which epigenetics is obviously central, due to the notion of memory of early decisional events during development even when this stimulus is gone, that is implied in Waddington's developmental concept. This review first summarizes the different mechanisms by which the environment can model the epigenome: receptor signalling, energy metabolism and signal mechanotransduction from extracellular matrix to chromatin. Then an overview of the epigenetic changes in response to maternal environment during the vulnerability time windows, gametogenesis, early development, placentation and foetal growth, and postnatal period, is described, with the specific example of overnutrition and food deprivation. The implication of epigenetics in DOHaD is obvious, however the precise causal chain from early environment to the epigenome modifications to the phenotype still needs to be deciphered.
Topics: Disease; Epigenome; Epigenomics; Genetic Predisposition to Disease; Humans; Parents; Phenotype; Signal Transduction
PubMed: 31587964
DOI: 10.1016/j.semcdb.2019.09.008 -
Clinical Pharmacokinetics 1985Serum drug concentration monitoring can be an invaluable aid to patient management, particularly in certain pathological conditions when individualisation of dosage is... (Review)
Review
Serum drug concentration monitoring can be an invaluable aid to patient management, particularly in certain pathological conditions when individualisation of dosage is particularly critical. To be clinically useful, however, drug levels must be interpreted in the context of all factors that could influence the correlation between the concentration of the drug in plasma and the intensity of action. Several such factors may be operating in acute and chronic disease states. For example, a number of pathological conditions are associated with marked changes in the fraction of free, pharmacologically active drug in plasma and this will result in disruption of the normal relationship between total serum drug level and effect, as seen for phenytoin in uraemia. An altered response to a given serum drug level in disease states may also be caused by changes in tissue distribution, by abnormal accumulation of pharmacologically active metabolites in plasma or by changes in end-organ responsiveness. The latter are best illustrated by the altered sensitivity to digoxin in patients with various conditions, including hypokalaemia and thyroid disease. In addition to the factors listed above, consideration should also be given to potential interactions with concomitantly used drugs and to the possibility of analytical errors, especially in view of the evidence that the performance of otherwise reliable drug assays may be grossly impaired in certain diseases (e.g. uraemia), due to abnormal plasma composition and/or accumulation of interfering metabolites. In view of these complexities, a correct interpretation of serum drug levels requires a good knowledge of clinical pharmacology and a close collaboration between physician and laboratory. In any case, serum drug concentrations, like other laboratory tests, are not a substitute for careful patient observation, and any decision about drug treatment should be primarily based upon evaluation of the clinical state and, whenever possible, direct measurement of drug effects.
Topics: Acute Disease; Biotransformation; Blood Proteins; Chronic Disease; Disease; Drug Interactions; Humans; Pharmaceutical Preparations; Protein Binding; Tissue Distribution; Uremia
PubMed: 3905165
DOI: 10.2165/00003088-198510060-00003 -
Journal of Cell Science Sep 2014The ATPase valosin-containing protein (VCP)/p97 has emerged as a central and important element of the ubiquitin system. Together with a network of cofactors, it... (Review)
Review
The ATPase valosin-containing protein (VCP)/p97 has emerged as a central and important element of the ubiquitin system. Together with a network of cofactors, it regulates an ever-expanding range of processes that stretch into almost every aspect of cellular physiology. Its main role in proteostasis and key functions in signaling pathways are of relevance to degenerative diseases and genomic stability. In this Cell Science at a Glance and the accompanying poster, we give a brief overview of this complex system. In addition, we discuss the pathogenic basis for VCP/p97-associated diseases and then highlight in more detail new exciting links to the translational stress response and RNA biology that further underscore the significance of the VCP/p97 system.
Topics: Adenosine Triphosphatases; Animals; Cell Cycle Proteins; Disease; Gene Expression Regulation; Humans; Pathology; Stress, Physiological; Valosin Containing Protein
PubMed: 25146396
DOI: 10.1242/jcs.093831 -
Biochemical Society Transactions Apr 2011Sensing and interpreting extracellular signals in response to changes in the environment has been a fundamental feature of all life forms from the very beginning of... (Review)
Review
Sensing and interpreting extracellular signals in response to changes in the environment has been a fundamental feature of all life forms from the very beginning of evolution. To fulfil this function, networks of proteins have evolved, forming the intracellular signal transduction machinery. Whereas the appropriate control of these signal transduction systems is essential to homoeostasis, dysregulation of signalling leads to disease and often the death of the organism. The tribbles family of pseudokinases have emerged in recent years as key controllers of signal transduction via their interactions with several key kinases, ubiquitin ligases and transcription factors. In line with their role in regulating fundamentally important signalling pathways, members of the tribbles family have been implicated in the development of a range of human diseases. Whereas our mechanistic understanding of how these proteins contribute to disease is far from complete, the present paper attempts to summarize some of the most important recent developments in this field of research.
Topics: Animals; Cell Physiological Phenomena; Cells; Disease; Humans; Intracellular Signaling Peptides and Proteins; Multigene Family; Protein Serine-Threonine Kinases; Signal Transduction
PubMed: 21428962
DOI: 10.1042/BST0390684 -
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 -
Medicinal Research Reviews Nov 2019Ongoing studies have determined that the gut microbiota is a major factor influencing both health and disease. Host genetic factors and environmental factors contribute... (Review)
Review
Ongoing studies have determined that the gut microbiota is a major factor influencing both health and disease. Host genetic factors and environmental factors contribute to differences in gut microbiota composition and function. Intestinal dysbiosis is a cause or a contributory cause for diseases in multiple body systems, ranging from the digestive system to the immune, cardiovascular, respiratory, and even nervous system. Investigation of pathogenesis has identified specific species or strains, bacterial genes, and metabolites that play roles in certain diseases and represent potential drug targets. As research progresses, gut microbiome-based diagnosis and therapy are proposed and applied, which might lead to considerable progress in precision medicine. We further discuss the limitations of current studies and potential solutions.
Topics: Disease; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Health; Humans; Molecular Targeted Therapy; Signal Transduction
PubMed: 30994937
DOI: 10.1002/med.21584