Molecular mechanisms in haematological malignancies

Haematopoiesis requires the constant production of large numbers of peripheral blood cells. This process is under tight control of transcription factor networks as well as cytokines, growth factors and hormones. We will review the importance of transcription factors in programming the haematopoietic lineage commitment and the role of the microenvironment and the corresponding cellular sensitivity to ensure production of mature functional cells in response to the physiological demand. Understanding the molecular mechanism of this complex process gives the opportunity to identify the underlying molecular deregulation in haematopoietic malignancies. The different levels of deregulation include hyperproliferation, block in differentiation and sensitivity to growth factors. In this review, leukaemic transformation is selected to give evidence of cell signalling deregulation. The clinical implications will be reviewed in the context of the potential opportunities in the future to identify specific therapeutic patient groups that can be defined using prognostic and predictive biomarkers.peer-reviewe

Molecular mechanisms of neural crest formation

The neural crest is a transient population of multipotent precursor cells named for its site of origin at the crest of the closing neural folds in vertebrate embryos. Following neural tube closure, these cells become migratory and populate diverse regions throughout the embryo where they give rise to most of the neurons and support cells of the peripheral nervous system (PNS), pigment cells, smooth muscle, craniofacial cartilage, and bone. Because of its remarkable ability to generate such diverse derivatives, the neural crest has fascinated developmental biologists for over one hundred years. A great deal has been learned about the migratory pathways neural crest cells follow and the signals that may trigger their differentiation, but until recently comparatively little was known about earlier steps in neural crest development. In the past few years progress has been made in understanding these earlier events, including how the precursors of these multipotent cells are specified in the early embryo and the mechanisms by which they become migratory. In this review, we first examine the mechanisms underlying neural crest induction, paying particular attention to a number of growth factor and transcription factor families that have been implicated in this process. We also discuss when and how the fate of neural crest precursors may diverge from those of nearby neural and epidermal populations. Finally, we review recent advances in our understanding of how neural crest cells become migratory and address the process of neural crest diversification

Molecular Mechanisms

Ectoine, a compatible solute and osmolyte, is known to be an effective protectant of biomolecules and whole cells against heating, freezing and extreme salinity. Protection of cells (human keratinocytes) by ectoine against ultraviolet radiation has also been reported by various authors, although the underlying mechanism is not yet understood. We present the first electron irradiation of DNA in a fully aqueous environment in the presence of ectoine and at high salt concentrations. The results demonstrate effective protection of DNA by ectoine against the induction of single-strand breaks by ionizing radiation. The effect is explained by an increase in low-energy electron scattering at the enhanced free- vibrational density of states of water due to ectoine, as well as the use of ectoine as an hydroxyl-radical scavenger. This was demonstrated by Raman spectroscopy and electron paramagnetic resonance (EPR)

Molecular mechanisms of autoimmunity triggered by microbial infection

Autoimmunity can be triggered by microbial infection. In this context, the discovery of Toll-like receptors (TLRs) provides new insights and research perspectives. TLRs induce innate and adaptive antimicrobial immune responses upon exposure to common pathogen-associated molecules, including lipopeptides, lipopolysaccharides, and nucleic acids. They also have the potential, however, to trigger autoimmune disease, as has been revealed by an increasing number of experimental reports. This review summarizes important facts about TLR biology, available data on their role in autoimmunity, and potential consequences for the management of patients with autoimmune disease

Molecular mechanisms regulating perivascular adipose tissue - potential pharmacological targets?

No abstract available

Computational modeling to elucidate molecular mechanisms of epigenetic memory

How do mammalian cells that share the same genome exist in notably distinct phenotypes, exhibiting differences in morphology, gene expression patterns, and epigenetic chromatin statuses? Furthermore how do cells of different phenotypes differentiate reproducibly from a single fertilized egg? These are fundamental problems in developmental biology. Epigenetic histone modifications play an important role in the maintenance of different cell phenotypes. The exact molecular mechanism for inheritance of the modification patterns over cell generations remains elusive. The complexity comes partly from the number of molecular species and the broad time scales involved. In recent years mathematical modeling has made significant contributions on elucidating the molecular mechanisms of DNA methylation and histone covalent modification inheritance. We will pedagogically introduce the typical procedure and some technical details of performing a mathematical modeling study, and discuss future developments.Comment: 36 pages, 4 figures, 2 tables, book chapte

Neuroinflammation and Its Resolution: From Molecular Mechanisms to Therapeutic Perspectives

Neuroinflammation, the complex immune response of the central nervous system (CNS), when sustained, is a common denominator in the etiology and course of all major neurological diseases, including neurodevelopmental, neurodegenerative, and psychiatric disorders (e.g., Alzheimer's disease, AD; Parkinson's disease, PD; multiple sclerosis, MS; motor neuron disease; depression; autism spectrum disorder; and schizophrenia). Cellular (microglia and mast cells, two brain-resident immune cells, together with astrocytes) and molecular immune components (e.g., cytokines, complement and patternrecognition receptors) act as key regulators of neuroinflammation (Skaper et al., 2012). In response to pathological triggers or neuronal damage, immune cells start an innate immune response with the aim to eliminate the initial cause of injury. However, when the cellular activity becomes dysregulated, it results in an inappropriate immune response that can be injurious and affect CNS functions. Thus, limiting neuroinflammation and microglia activity represents a potential strategy to alleviate neuroinflammationrelated diseases. The Research Topic collects 20 manuscripts, divided into five sections, that include both original research articles and reviews of the emerging literature and explore the role of neuroinflammation in various neurological diseases. There is particular attention dedicated to the relevant research exploring the mechanisms and mediators involved in the resolution of neuroinflammation. Our aim was to generate a valuable discussion contributing to identify new therapeutic targets in brain damage and providing new drug development opportunities for the prevention and treatment of CNS diseases involving neuroinflammation

Novel Molecular Mechanisms in the Development of Non-Alcoholic Steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in adults and children worldwide. NAFLD has become a severe health issue and it can progress towards a more severe form of the disease, the non-alcoholic steatohepatitis (NASH). A combination of environmental factors, host genetics, and gut microbiota leads to excessive accumulation of lipids in the liver (steatosis), which may result in lipotoxicity and trigger hepatocyte cell death, liver inflammation, fibrosis, and pathological angiogenesis. NASH can further progress towards liver cirrhosis and cancer. Over the last few years, cell-derived extracellular vesicles (EVs) have been identified as effective cell-to-cell messengers that transfer several bioactive molecules in target cells, modulating the pathogenesis and progression of NASH. In this review, we focused on recently highlighted aspects of molecular pathogenesis of NASH, mediated by EVs via their bioactive components. The studies included in this review summarize the state of art regarding the role of EVs during the progression of NASH and bring novel insight about the potential use of EVs for diagnosis and therapeutic strategies for patients with this disease