2,715 research outputs found
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Evidence linking exposure of fish primary macrophages to antibiotics activates the NF-kB pathway.
Low doses of antibiotics are ubiquitous in the marine environment and may exert negative effects on non-target aquatic organisms. Using primary macrophages of common carp, we investigated the mechanisms of action following exposure to several common antibiotics; cefotaxime, enrofloxacin, tetracycline, sulfamonomethoxine, and their mixtures, and explored the immunomodulatory effects associated with the nuclear factor-κB (NF-κB) signaling pathway. A KEGG pathway analysis was conducted using the sixty-six differentially expressed genes found in all treatments, and showed that exposure to 100 μg/L of antibiotics could affect regulation of the NF-κB signaling pathway, suggesting that activation of NF-κB is a common response in all four classes of antibiotics. In addition, the four antibiotics induced nf-κb and NF-κB-associated cytokines expression, as verified by qPCR, however, these induction responses by four antibiotics were minor when compared to the same concentration of LPS treatment (100 μg/L). Antagonists of NF-κB blocked many of the immune effects of the antibiotics, providing evidence that NF-κB pathways mediate the actions of all four antibiotics. Moreover, exposure to environmentally relevant, low levels (0.01-100 μg/L) of antibiotics induced a NF-κB-mediated immune response, including endogenous generation of ROS, activity of antioxidant enzymes, as well as expression of cytokine and apoptosis. Moreover, exposure to mixtures of antibiotics presented greater effects on most tested immunological parameters than exposure to a single antibiotic, suggesting additive effects from multiple antibiotics in the environment. This study demonstrates that exposure of fish primary macrophages to low doses of antibiotics activates the NF-kB pathway
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Leveraging Microtechnology to Study Multicellular Microvascular Systems and Macromolecular Interaction
Biological systems are large-scale, complex systems comprised of many hierarchical subsystems interacting physico-chemically in a dynamic and coordinated fashion. The complex interactions of subsystems (in micro-scale) lead to the formation of emergent properties (in macro-scale); these are properties that are not visible if individual subsystems are studied. The inherent high-throughput characteristics of microfabrication technology (microtechnology) along with its ability to manipulate biological species at the micro-scale makes it an ideal tool to elucidate the mechanisms leading to the formation of emergent properties at the macro-scale.
In this dissertation, by combining microtechnologies with advanced computational algorithms, we demonstrate system-level analysis of biological systems in development and disease. The abundance of high quality molecular and genetic data along with the drastic increase in computational power resulted in considerable progress in genomics, epigenomics and proteomics, but not for the so-called cellomics as we define it here: high-throughput study of single-cell phenotype and heterotypic cell-cell interaction via micromanipulation and bioinformatics analysis. Lack of high-throughput robust experimental tools is the major roadblock to cellomics. Using microtechnologies, in the context of developmental biology we studied vascular tissue morphogenesis (vasculogenesis). Formation of microvessels is of critical significance in development and for vascularizing newly engineered tissues in regenerative medicine.
First, we sought to map the heterogeneous morphodynamic behavior of individual clonal cells in the process of capillary-like structure (CLS) formation (Chapter 2 and 3). Then we looked into deciphering the role of extracellular matrix (ECM) mediated mechanical signals in deriving the process of CLS formation (Chapter 4). In the second half of this thesis, we demonstrated the capabilities of microtechnologies and advanced computational algorithms in tackling the challenging problems in disease: global health diagnostics and cancer drug screening.
First, we studied the performance of microfluidic-based diagnostic as a large-scale complex system under real-world constraints (Chapter 5). Then, we present the development of two microfluidic-based platforms to study the heterotypic interaction of cells in both a biomimetic in vitro and a realistic in vivo setting. We developed an implantable construct carrying a densely-packed heterogeneous panel of tumor cells. This platform could ultimately be used to test anti-cancer drug efficacy against a large number of genotypes in an in vivo setting (Appendices A and B).
Together, these methods provide a powerful suite of tools for high-throughput analysis of biological species at the micro-scale and could potentially unlock the mysteries behind the emergent properties observed at the macro-scale
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Spectral imaging in preclinical research and clinical pathology.
Spectral imaging methods are attracting increased interest from researchers and practitioners in basic science, pre-clinical and clinical arenas. A combination of better labeling reagents and better optics creates opportunities to detect and measure multiple parameters at the molecular and cellular level. These tools can provide valuable insights into the basic mechanisms of life, and yield diagnostic and prognostic information for clinical applications. There are many multispectral technologies available, each with its own advantages and limitations. This chapter will present an overview of the rationale for spectral imaging, and discuss the hardware, software and sample labeling strategies that can optimize its usefulness in clinical settings
Prospects of Nanotechnology in Clinical Immunodiagnostics
Nanostructured materials are promising compounds that offer new opportunities as sensing platforms for the detection of biomolecules. Having micrometer-scale length and nanometer-scale diameters, nanomaterials can be manipulated with current nanofabrication methods, as well as self-assembly techniques, to fabricate nanoscale bio-sensing devices. Nanostructured materials possess extraordinary physical, mechanical, electrical, thermal and multifunctional properties. Such unique properties advocate their use as biomimetic membranes to immobilize and modify biomolecules on the surface of nanoparticles. Alignment, uniform dispersion, selective growth and diameter control are general parameters which play critical roles in the successful integration of nanostructures for the fabrication of bioelectronic sensing devices. In this review, we focus on different types and aspects of nanomaterials, including their synthesis, properties, conjugation with biomolecules and their application in the construction of immunosensing devices. Some key results from each cited article are summarized by relating the concept and mechanism behind each sensor, experimental conditions and the behavior of the sensor under different conditions, etc. The variety of nanomaterial-based bioelectronic devices exhibiting novel functions proves the unique properties of nanomaterials in such sensing devices, which will surely continue to expand in the future. Such nanomaterial based devices are expected to have a major impact in clinical immunodiagnostics, environmental monitoring, security surveillance and for ensuring food safety
Proteins in stool as biomarkers for non-invasive detection of colorectal adenomas with high risk of progression
Screening to detect colorectal cancer (CRC) in an early or premalignant state is an effective method to reduce CRC mortality rates. Current stool-based screening tests, e.g. fecal immunochemical test (FIT), have a suboptimal sensitivity for colorectal adenomas and difficulty distinguishing adenomas at high risk of progressing to cancer from those at lower risk. We aimed to identify stool protein biomarker panels that can be used for the early detection of high-risk adenomas and CRC. Proteomics data (LC–MS/MS) were collected on stool samples from adenoma (n = 71) and CRC patients (n = 81) as well as controls (n = 129). Colorectal adenoma tissue samples were characterized by low-coverage whole-genome sequencing to determine their risk of progression based on specific DNA copy number changes. Proteomics data were used for logistic regression modeling to establish protein biomarker panels. In total, 15 of the adenomas (15.8%) were defined as high risk of progressing to cancer. A protein panel, consisting of haptoglobin (Hp), LAMP1, SYNE2, and ANXA6, was identified for the detection of high-risk adenomas (sensitivity of 53% at specificity of 95%). Two panels, one consisting of Hp and LRG1 and one of Hp, LRG1, RBP4, and FN1, were identified for high-risk adenomas and CRCs detection (sensitivity of 66% and 62%, respectively, at specificity of 95%). Validation of Hp as a biomarker for high-risk adenomas and CRCs was performed using an antibody-based assay in FIT samples from a subset of individuals from the discovery series (n = 158) and an independent validation series (n = 795). Hp protein was significantly more abundant in high-risk adenoma FIT samples compared to controls in the discovery (p = 0.036) and the validation series (p = 9e-5). We conclude that Hp, LAMP1, SYNE2, LRG1, RBP4, FN1, and ANXA6 may be of value as stool biomarkers for early detection of high-risk adenomas and CRCs
Methods for immobilizing receptors in microfluidic devices: A review
In this review article, we discuss state-of-the-art methods for immobilizing functional receptors in microfluidic devices. Strategies used to immobilize receptors in such devices are essential for the development of specific, sensitive (bio)chemical assays that can be used for a wide range of applications. In the first section, we review the principles and the chemistry of immobilization techniques that are the most commonly used in microfluidics. We afterward describe immobilization methods on static surfaces from microchannel surfaces to electrode surfaces with a particular attention to opportunities offered by hydrogel surfaces. Finally, we discuss immobilization methods on mobile surfaces with an emphasis on both magnetic and non-magnetic microbeads, and finally, we highlight recent developments of new types of mobile supports
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