Project description:Acute phase reactants serum amyloid A-1, 3 and micro RNA-135b, -449a, and -1 are induced in lungs of mice exposed to subtoxic doses of nano-titanium dioxide particles by inhalation In the present study we investigate pulmonary mRNA and miRNA profiles of mice exposed to subtoxic dose of nano-titanium dioxide particles by inhalation. We show dramatic induction of acute phase reactants, chemoattractants, immune and host defence related genes. We also demonstrate for the first time changes in miRNA profiles in the lungs in response to nanoTiO2. Keywords: Toxicology, disease state analysis, biomarkers of health effects
Project description:Our objective was to investigate epigenomic and transcriptomic changes in J774 macrophages after incubation with talc and titanium dioxide particles. This dataset comprises the results of reduced representation bisulfite sequencing (RRBS) of the J774 cell DNA 24 hours after exposure to 10 ug/well of fine-sized talc or titanium dioxide particles in vitro with or without 2 ug/mL 17-b estradiol.
Project description:We performed a high throughput RNA sequencing to evaluate the expression profiles of messenger RNAs (mRNAs) and non-coding RNAs (lncRNAs, miRNAs, and circRNAs) in Titanium (Ti) particles induced inflammatory responses using RAW264.7 cells.
Project description:Rationale: Maternal immune responses can promote allergy development in offspring. Pilot data show that neonates of mother mice exposed during pregnancy to air pollution particles have increased allergic susceptibility. Objective: We investigated whether inflammatory response to titanium dioxide (TiO2) particles earlier considered immunologically ‘inert’ is enhanced during pregnancy. Methods: Pregnant BALB/c mice (or non-pregnant controls) received particle suspensions intranasally at day 14 of pregnancy. Lung inflammatory responses were evaluated 19 and 48 h after exposure. Results: Pregnant mice showed robust and persistent acute inflammatory responses after exposure to TiO2, while non-pregnant females had the expected minimal responses. Genomic profiling identified genes differentially expressed in pregnant lungs exposed to TiO2. Neonates of mothers exposed to TiO2 (but not PBS) developed increased susceptibility to allergens. Conclusion: Pregnancy enhances lung inflammatory responses to otherwise relatively innocuous inert particles. Keywords: Particles exposure, pregnancy vs normal
Project description:Acute phase reactants serum amyloid A-1, 3 and micro RNA-135b, -449a, and -1 are induced in lungs of mice exposed to subtoxic doses of nano-titanium dioxide particles by inhalation In the present study we investigate pulmonary mRNA and miRNA profiles of mice exposed to subtoxic dose of nano-titanium dioxide particles by inhalation. We show dramatic induction of acute phase reactants, chemoattractants, immune and host defence related genes. We also demonstrate for the first time changes in miRNA profiles in the lungs in response to nanoTiO2. Keywords: Toxicology, disease state analysis, biomarkers of health effects Female C57BL/6 mice were exposed to 40 mg nanoTiO2/m3 for one hour/day for 11 consecutive days and were sacrificed 5 days following the last exposure. Left lung lobes and liver were removed and flash frozen. Total RNA was isolated from a small random part of the frozen lung and liver and was hybridized against universal mouse reference RNA to Agilent Oligo DNA microarrays (Agilent Technologies) containing 44,000 transcripts. Microarrays were normalized using a global LOWESS approach and analyzed by MAANOVA 2.0 and SAM. Microarray results were validated by real time RT-PCR. Impact of alteration in expression of select genes was further validated by analysing their total protein levels in lung tissue homogenates.
Project description:Titanium is a common implant material. However, in some patients titanium implants fail. Macrophages are key cells involved in foreign body response. To identify macrophage response to titainum, primary human macrophages were cultured on polished titanium discs for 6 days We used microarrays to determine the global expression pattern induced by polished titanium in macrophages and identify potential genes involved in implant failure.
Project description:Titanium is a common implant material. However, in some patients titanium implants fail. Macrophages are key cells involved in foreign body response. To identify macrophage response to titainum, primary human macrophages were cultured on porous titanium discs for 6 days We used microarrays to determine the global expression pattern induced by porous titanium in macrophages and identify potential genes involved in implant failure.
Project description:Aseptic loosening represents a significant factor contributing to joint replacement failure, primarily associated with diminished bone formation and heightened osteoclast-induced osteolysis. Here, a natural polymer-based injectable hydrogel that encapsulates irisin protein (referred to as I-OG hydrogel) is reported. The hierarchical cross-linked structure of the I-OG hydrogel confers favorable mechanical properties, desirable self-healing ability, and acceptable injectability and, more importantly, sustains continuous release of the protein at the interface between the bone and implant prosthesis. The I-OG hydrogel effectively fills the gap between the titanium pin and bone tissue, successfully inhibiting aseptic loosening induced by titanium particles, which outcome confirms the occurrence of irisin protein's slow-release process and its inhibitory effect on osteolysis. Mechanistically, our in vitro experiments demonstrated that irisin released from the I-OG hydrogel upregulates the Wnt/β-catenin signaling pathway in bone marrow stromal cells (BMSCs) through integrin αV, while concurrently downregulating the NF-κB (P65) signaling pathway in osteoblasts. These molecular events ultimately promote osteogenic differentiation and inhibit osteoclast activation. Collectively, our findings establish that the I-OG hydrogel effectively counteracts aseptic loosening by resisting osteolysis caused by titanium particles and enhancing periprosthetic bone formation, and offers promising prospects for the treatment of aseptic loosening in prosthetic implants.
Project description:The toxicity and toxicogenomics of selected anatase and rutile nanoparticles (NP) and bulk titanium dioxide (TiO2) particles were evaluated in the soil nematode Caenorhabditis elegans. Results indicated that bulk or nano-TiO2 particles were slightly toxic to soil nematode C. elegans, as measured by reproduction EC50 values ranging from 4 to 32 mg/L. Whole-genome microarray results indicated that the regulation of glutathione-S-transferase gst-3, cytochrome P450 cypp33-c11, stress resistance regulator scl-1, oxidoreductase wah-1, and embryonic development pod-2 genes were significantly affected by nano-sized and bulk TiO2 particles. More specifically, it was determined that anatase particles exerted a greater effect on metabolic pathways, whereas rutile particles had a greater effect on developmental processes. The up-regulation of the pod-2 gene corroborated the phenotypic effect observed in the reproduction test. Our results demonstrated that C. elegans is a good genomic model for nano-TiO2 toxicity assessment.