Adv Exp Med Biol
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In chronic airway inflammatory disorders, such as asthma, glucocorticoid (GC) insensitivity is a challenging clinical problem associated with life-threatening disease progression and the potential development of serious side effects. The mechanism of steroid resistance in asthma remains unclear and may be multifactorial. Excluding noncompliance with GC treatment, abnormal steroid pharmacokinetics, and rare genetic defects in the glucocorticoid receptor (GR), the majority of GC insensitivity in asthma can be attributed to secondary defects related to GR function. ⋯ Since T cells, eosinophils, and monocytes play a major role in the pathogenesis of airway inflammation, most of the work published to date has focused on these cell types as the primary therapeutic targets in GC-insensitive asthma. We herein review several distinct techniques for the assessment of (1) the cellular response to GCs including the effect of GCs on cell viability, adhesion, and mediator release; (2) the functionality of GC receptors, including phosphorylation of the GR, nuclear translocation, and binding activities; and (3) the characterization of proteins differentially expressed in steroid-resistant cells by comparative 2DE-gel electrophoresis-based techniques and mass spectrometry. These comprehensive approaches are expected to reveal novel candidates for biomarkers of steroid insensitivity, which may lead to the development of effective therapeutic interventions for patients with chronic steroid-resistant asthma.
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Review
Nanoceria as bona fide catalytic antioxidants in medicine: what we know and what we want to know….
Cerium oxide (CeO2) nanoparticles, CeNPs or nanoceria are inorganic and possess catalytic antioxidant activity. They scavenge reactive oxygen species and act as an oxygen buffer. Their application in industry is well-established. ⋯ We highlight studies that examine how CeNPs behave in biological environments and how they interact with bio-macromolecules. We also discuss studies that examine the dynamic changes of the surface chemistry of CeNPs in physiological buffers. Finally, we raise a list of questions that we think ought to be answered for CeNPs to be considered the antioxidants of choice in medicine, specifically in the treatment of ocular diseases.
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Once viewed as part of the "dark matter" of genome, long noncoding RNAs (lncRNAs), which are mRNA-like but lack open reading frames, have emerged as an integral part of the mammalian transcriptome. Recent work demonstrated that lncRNAs play multiple structural and functional roles, and their analysis has become a new frontier in biomedical research. In this chapter, we provide an overview of different lncRNA families, describe methodologies available to study lncRNA-protein and lncRNA-DNA interactions systematically, and use well-studied lncRNAs as examples to illustrate their functional importance during normal development and in disease states.
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Neuropeptides are important mediators both within the nervous system and between neurons and other cell types. Neuropeptides such as substance P, calcitonin gene-related peptide and neuropeptide Y (NPY), vasoactive intestinal polypeptide, somatostatin and corticotropin-releasing factor are also likely to play a role in the bidirectional gut-brain communication. In this capacity they may influence the activity of the gastrointestinal microbiota and its interaction with the gut-brain axis. ⋯ While PYY is almost exclusively expressed by enteroendocrine cells, NPY is found at all levels of the gut-brain and brain-gut axis. The function of PYY-releasing enteroendocrine cells is directly influenced by short chain fatty acids generated by the intestinal microbiota from indigestible fibre, while NPY may control the impact of the gut microbiota on inflammatory processes, pain, brain function and behaviour. Although the impact of neuropeptides on the interaction between the gut microbiota and brain awaits to be analysed, biologically active peptides are likely to emerge as neural and endocrine messengers in orchestrating the microbiota-gut-brain axis in health and disease.
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In general protein posttranslation modifications (PTMs) involve the covalent addition of functional groups or molecules to specific amino acid residues in proteins. These modifications include phosphorylation, glycosylation, S-nitrosylation, acetylation, lipidation, among others (Angew Chem Int Ed Engl 44(45):7342-7372, 2005). Although other amino acids can undergo different kinds of oxidative posttranslational modifications (oxPTMs) (Exp Gerontol 36(9):1495-1502, 2001), in this chapter oxPTM will be considered specifically related to Cysteine oxidation, and redox proteomics here is translated as a comprehensive investigation of oxPTMs, in biological systems, using diverse technical approaches. ⋯ Therefore, the identification and localization of oxPTMs within cellular milieu became critical to understand redox regulation of proteins in physiological and pathological conditions, and consequently an important information to develop better strategies for treatment and prevention of diseases associated with oxidative stress. There is a wide range of techniques available to investigate oxPTMs, including gel-based and non-gel-based separation approaches to be combined with sophisticated methods of detection, identification, and quantification of these modifications. The strategies and approaches to study oxPTMs and the respective applications related to physiological and pathological conditions will be discussed in more detail in this chapter.