An ancestral molecular response to nanomaterial particulates.
Ontology highlight
ABSTRACT:
SUBMITTER: Del Giudice G
PROVIDER: S-EPMC10427433 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
Publications
An ancestral molecular response to nanomaterial particulates.
Del Giudice G G Serra A A Saarimäki L A LA Kotsis K K Rouse I I Colibaba S A SA Jagiello K K Mikolajczyk A A Fratello M M Papadiamantis A G AG Sanabria N N Annala M E ME Morikka J J Kinaret P A S PAS Voyiatzis E E Melagraki G G Afantitis A A Tämm K K Puzyn T T Gulumian M M Lobaskin V V Lynch I I Federico A A Greco D D
Nature nanotechnology 20230508 8
The varied transcriptomic response to nanoparticles has hampered the understanding of the mechanism of action. Here, by performing a meta-analysis of a large collection of transcriptomics data from various engineered nanoparticle exposure studies, we identify common patterns of gene regulation that impact the transcriptomic response. Analysis identifies deregulation of immune functions as a prominent response across different exposure studies. Looking at the promoter regions of these genes, a se ...[more]
Similar Datasets
Project description:Polarization of immune cells is commonly observed in host responses associated with microbial immunity, inflammation, tumorigenesis, and tissue repair and fibrosis. In this process, immune cells adopt distinct programs and perform specialized functions in response to specific signals. Accumulating evidence indicates that inhalation of micro- and nano-sized particulates activates barrier immune programs in the lung in a time- and context-dependent manner, including type 1 and type 2 inflammation, and T helper (Th) 17 cell, regulatory T cell (Treg), innate lymphoid cell (ILC), and myeloid-derived suppressor cell (MDSC) responses, which highlight the polarization of several major immune cell types. These responses facilitate the pulmonary clearance and repair under physiological conditions. When exposure persists and overwhelms the clearance capacity, they foster the chronic progression of inflammation and development of progressive disease conditions, such as fibrosis and cancer. The pulmonary response to insoluble particulates thus represents a distinctive disease process wherein non-infectious, persistent exposures stimulate the polarization of immune cells to orchestrate dynamic inflammatory and immune reactions, leading to pulmonary and pleural chronic inflammation, fibrosis, and malignancy. Despite large variations in particles and their associated disease outcomes, the early response to inhaled particles often follows a common path. The initial reactions entail a barrier immune response dominated by type 1 inflammation that features active phagocytosis by M1 macrophages and recruitment of neutrophils, both of which are fueled by Th1 and proinflammatory cytokines. Acute inflammation is immediately followed by resolution and tissue repair mediated through specialized pro-resolving mediators (SPMs) and type 2 cytokines and cells including M2 macrophages and Th2 lymphocytes. As many particles and fibers cannot be digested by phagocytes, resolution is often extended and incomplete, and type 2 inflammation becomes heightened, which promotes interstitial fibrosis, granuloma formation, and tumorigenesis. Recent studies also reveal the involvement of Th17-, Treg-, ILC-, and MDSC-mediated responses in the pathogenesis caused by inhaled particulates. This review synopsizes the progress in understanding the interplay between inhaled particles and the pulmonary immune functions in disease pathogenesis, with focus on particle-induced polarization of immune cells and its role in the development of chronic inflammation, fibrosis, and cancer in the lung.
| S-EPMC7311785 | biostudies-literature
Project description:Nanotechnology is employed across a wide range of antibacterial applications in clinical settings, food, pharmaceutical and textile industries, water treatment and consumer goods. Depending on type and concentration, engineered nanomaterials (ENMs) can also benefit bacteria in myriad contexts including within the human body, in biotechnology, environmental bioremediation, wastewater treatment, and agriculture. However, to realize the full potential of nanotechnology across broad applications, it is necessary to understand conditions and mechanisms of detrimental or beneficial effects of ENMs to bacteria. To study ENM effects, bacterial population growth or viability are commonly assessed. However, such endpoints alone may be insufficiently sensitive to fully probe ENM effects on bacterial physiology. To reveal more thoroughly how bacteria respond to ENMs, molecular-level omics methods such as transcriptomics, proteomics, and metabolomics are required. Because omics methods are increasingly utilized, a body of literature exists from which to synthesize state-of-the-art knowledge. Here we review relevant literature regarding ENM impacts on bacterial cellular pathways obtained by transcriptomic, proteomic, and metabolomic analyses across three growth and viability effect levels: inhibitory, sub-inhibitory or stimulatory. As indicated by our analysis, a wider range of pathways are affected in bacteria at sub-inhibitory vs. inhibitory ENM effect levels, underscoring the importance of ENM exposure concentration in elucidating ENM mechanisms of action and interpreting omics results. In addition, challenges and future research directions of applying omics approaches in studying bacterial-ENM interactions are discussed.
| S-EPMC8236600 | biostudies-literature
Project description:Tobacco smoke (TS) is the source of a number of toxicants affecting the atmosphere and poses a threat to smokers and the whole community. Chemical, physical, and toxicological features of smoking products (vapors as well as mainstream, side stream, and third-hand smoke) have been investigated extensively. Special attention is paid to organic compounds (individually or in combination giving rise to peculiar molecular fingerprints), potentially able to act as "chemical signature" of TS. In this regard, the percent distribution of long-chainnormal, iso, and anteiso alkanes was ascertained as typical of TS. Nevertheless, until now no indexes have been identified as suitable for assessing the global TS contribution to environmental pollution, e.g., the TS percentage in carbonaceous aerosol and in deposited dusts, the only exception consisting in the use of nicotelline as tracer. This paper describes the results of an extensive study aimed at chemically characterizing the nonpolar lipid fraction associated to suspended particulates (PMs) and deposition dusts (DDs) collected at indoor and outdoor locations. Based on the iso, anteiso, and normal C29-C34 alkane profile in the samples as well in tobacco smoke- and no-TS-related emissions (literature data), various parameters describing the distribution of compounds were investigated. Finally, a cumulative variable was identified as the tobacco smoke impact index (TS%) suitable for estimating the TS percentage occurring in the particulate matter. The TS% rates were plotted vs. the exceedance of normal C31 alkane with respect to the average of C29 and C33 homologs, which results higher in TS than in most other emissions, revealing a link in the case of suspended particulates but not of deposited dusts. According to back analysis carried out on all particulate matter sets, it was found that traces of TS affect even remote areas, while inside the smokers' homes the contributions of TS to PM could account for up to ~61% and ~10%, respectively, in PM and DD. This confirms the need of valuing the health risk posed by TS to humans, by means of tools easy to apply in extensive investigations.
| S-EPMC8799971 | biostudies-literature
Project description:Elasmobranch fishes, including sharks, rays, and skates, use specialized electrosensory organs called ampullae of Lorenzini to detect extremely small changes in environmental electric fields. Electrosensory cells within these ampullae can discriminate and respond to minute changes in environmental voltage gradients through an unknown mechanism. Here we show that the voltage-gated calcium channel CaV1.3 and the big conductance calcium-activated potassium (BK) channel are preferentially expressed by electrosensory cells in little skate (Leucoraja erinacea) and functionally couple to mediate electrosensory cell membrane voltage oscillations, which are important for the detection of specific, weak electrical signals. Both channels exhibit unique properties compared with their mammalian orthologues that support electrosensory functions: structural adaptations in CaV1.3 mediate a low-voltage threshold for activation, and alterations in BK support specifically tuned voltage oscillations. These findings reveal a molecular basis of electroreception and demonstrate how discrete evolutionary changes in ion channel structure facilitate sensory adaptation.
| S-EPMC5354974 | biostudies-literature
Project description:The lumen of the small intestine (SI) is filled with particulates: microbes, therapeutic particles, and food granules. The structure of this particulate suspension could impact uptake of drugs and nutrients and the function of microorganisms; however, little is understood about how this suspension is re-structured as it transits the gut. Here, we demonstrate that particles spontaneously aggregate in SI luminal fluid ex vivo. We find that mucins and immunoglobulins are not required for aggregation. Instead, aggregation can be controlled using polymers from dietary fiber in a manner that is qualitatively consistent with polymer-induced depletion interactions, which do not require specific chemical interactions. Furthermore, we find that aggregation is tunable; by feeding mice dietary fibers of different molecular weights, we can control aggregation in SI luminal fluid. This work suggests that the molecular weight and concentration of dietary polymers play an underappreciated role in shaping the physicochemical environment of the gut.Editorial noteThis article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
| S-EPMC6342521 | biostudies-literature
Project description:Elasmobranch fishes, including sharks, rays, and skates, use specialized electrosensory organs called Ampullae of Lorenzini to detect extremely small changes in environmental electric fields. Electrosensory cells within these ampullae are able to discriminate and respond to minute changes in environmental voltage gradients through an as-yet unknown mechanism. Here we show that the voltage-gated calcium channel CaV1.3 and big conductance calcium-activated potassium (BK) channel are preferentially expressed by electrosensory cells in little skate (Leucoraja erinacea) and functionally couple to mediate electrosensory cell membrane voltage oscillations, which are important in the detection of specific, weak electrical signals. Both channels exhibit unique properties compared with their mammalian orthologues to support electrosensory functions: structural adaptations in CaV1.3 mediate a low voltage threshold for activation, while alterations in BK support specifically tuned voltage oscillations. These findings reveal a molecular basis of electroreception and demonstrate how discrete evolutionary changes in ion channel structure facilitate sensory adaptation.
2017-03-01 | GSE93582 | GEO
Project description:PurposeTo determine the effects of airborne particulate matter (PM) <2.5 µm in vitro and on the normal and Pseudomonas aeruginosa (PA)-infected cornea.MethodsAn MTT viability assay tested the effects of PM2.5 on mouse corneal epithelial cells (MCEC) and human corneal epithelial cells (HCET). MCEC were tested for reactive oxygen species using a 2',7'-dichlorodihydrofluorescein assay; RT-PCR determined mRNA levels of inflammatory and oxidative stress markers in MCEC (HMGB1, toll-like receptor 2, IL-1β, CXCL2, GPX1, GPX2, GR1, superoxide dismutase 2, and heme oxygenase 1) and HCET (high mobility group box 1, CXCL2, and IL-1β). C57BL/6 mice also were infected and after 6 hours, the PM2.5 was topically applied. Disease was graded by clinical score and evaluated by histology, plate count, myeloperoxidase assay, RT-PCR, ELISA, and Western blot.ResultsAfter PM2.5 (25-200 µg/mL), 80% to 90% of MCEC and HCET were viable and PM exposure increased reactive oxygen species in MCEC and mRNA expression levels for inflammatory and oxidative stress markers in mouse and human cells. In vivo, the cornea of PA+PM2.5 exposed mice exhibited earlier perforation over PA alone (confirmed histologically). In cornea, plate counts were increased after PA+PM2.5, whereas myeloperoxidase activity was significantly increased after PA+PM2.5 over other groups. The mRNA levels for several proinflammatory and oxidative stress markers were increased in the cornea in the PA+PM2.5 over other groups; protein levels were elevated for high mobility group box 1, but not toll-like receptor 4 or glutathione reductase 1. Uninfected corneas treated with PM2.5 did not differ from normal.ConclusionsPM2.5 triggers reactive oxygen species, upregulates mRNA levels of oxidative stress, inflammatory markers, and high mobility group box 1 protein, contributing to perforation in PA-infected corneas.
| S-EPMC7401652 | biostudies-literature
Project description:Ancient components of the ribosome, inferred from a consensus of previous work, were constructed in silico, in vitro and in vivo. The resulting model of the ancestral ribosome presented here incorporates ∼20% of the extant 23S rRNA and fragments of five ribosomal proteins. We test hypotheses that ancestral rRNA can: (i) assume canonical 23S rRNA-like secondary structure, (ii) assume canonical tertiary structure and (iii) form native complexes with ribosomal protein fragments. Footprinting experiments support formation of predicted secondary and tertiary structure. Gel shift, spectroscopic and yeast three-hybrid assays show specific interactions between ancestral rRNA and ribosomal protein fragments, independent of other, more recent, components of the ribosome. This robustness suggests that the catalytic core of the ribosome is an ancient construct that has survived billions of years of evolution without major changes in structure. Collectively, the data here support a model in which ancestors of the large and small subunits originated and evolved independently of each other, with autonomous functionalities.
| S-EPMC3597689 | biostudies-literature
Project description:In recent years, with the widespread use of TiO2-GO nanocomposite in industry, especially in the remediation of water environments, its toxic effects on aquatic organisms have received increasing attention. As molting is extremely important for crustaceans in their growth, in this study, we cloned the full-length cDNA sequences of two key genes related to molting, nuclear hormone receptor E75 (E75) and nuclear hormone receptor HR3 (HR3), in Macrobrachium rosenbergii, examined the gene expression profile, and investigated their toxicological effects on crustacean molting through nanomaterial exposure. The amino acid sequences for E75 and HR3 were respectively determined to encode 1138 and 363 acid residues. Sequence analysis showed that both E75 and HR3 contain a HOLI domain, with the E75 of M. rosenbergii being more closely related to the E75 of Palaemon carinicauda. These two genes were expressed at the highest levels in muscle, followed by hepatopancreas. The results showed that the expressions of E75 and HR3 in hepatopancreas and muscle tissues were significantly decreased after exposure to 0.1 mg/L of TiO2-GO composite nanoparticles (P < 0.05). This study will serve as a foundation for subsequent research into the evaluation of nanomaterial toxicity on crustacean species.
| S-EPMC10300099 | biostudies-literature
Project description:Molecular modeling and simulation are invaluable tools for nanoscience that predict mechanical, physicochemical, and thermodynamic properties of nanomaterials and provide molecular-level insight into underlying mechanisms. However, building nanomaterial-containing systems remains challenging due to the lack of reliable and integrated cyberinfrastructures. Here we present Nanomaterial Modeler in CHARMM-GUI, a web-based cyberinfrastructure that provides an automated process to generate various nanomaterial models, associated topologies, and configuration files to perform state-of-the-art molecular dynamics simulations using most simulation packages. The nanomaterial models are based on the interface force field, one of the most reliable force fields (FFs). The transferability of nanomaterial models among the simulation programs was assessed by single-point energy calculations, which yielded 0.01% relative absolute energy differences for various surface models and equilibrium nanoparticle shapes. Three widely used Lennard-Jones (LJ) cutoff methods are employed to evaluate the compatibility of nanomaterial models with respect to conventional biomolecular FFs: simple truncation at r = 12 Å (12 cutoff), force-based switching over 10 to 12 Å (10-12 fsw), and LJ particle mesh Ewald with no cutoff (LJPME). The FF parameters with these LJ cutoff methods are extensively validated by reproducing structural, interfacial, and mechanical properties. We find that the computed density and surface energies are in good agreement with reported experimental results, although the simulation results increase in the following order: 10-12 fsw <12 cutoff < LJPME. Nanomaterials in which LJ interactions are a major component show relatively higher deviations (up to 4% in density and 8% in surface energy differences) compared with the experiment. Nanomaterial Modeler's capability is also demonstrated by generating complex systems of nanomaterial-biomolecule and nanomaterial-polymer interfaces with a combination of existing CHARMM-GUI modules. We hope that Nanomaterial Modeler can be used to carry out innovative nanomaterial modeling and simulations to acquire insight into the structure, dynamics, and underlying mechanisms of complex nanomaterial-containing systems.
| S-EPMC8752518 | biostudies-literature