Project description:In recent years, the toxicity of graphene-related materials (GRMs) has been evaluated in diverse models to guarantee their safety. In most applications, sublethal doses of GRMs contact human barriers such as skin in a subchronic way. Herein, the subchronic effect (30 day exposure) of three GRMs (GO 1, GO 2, and FLG) with different oxidation degrees and sizes was studied. The effects of these materials on human skin cells, HaCaTs, were assayed through high-throughput metabolic-based readout and other cell-based assays. A differential effect was found between the different GRMs. GO 2 induced a metabolic remodeling in epithelial cells, increasing the level of tricarboxylic acid components, mirrored by increased cell proliferation and changes in cell phenotype. The oxidation degree, size, and method of manufacture of GRMs dictated harmful effects on cell metabolism and behavior generated by nontoxic exposures. Therefore, a "safe by design" procedure is necessary when working with these nanomaterials.
Project description:Microplastics are defined as plastics ranging in size from 0.1μm to 5mm. Currently, research is being conducted across various fields to examine the effects of microplastics. Some studies demonstrated negative impacts on cells and mice. However, there is a lack of research on the effects by long-term exposure to microplastics. Most of the papers evaluated cytotoxicity with period of less than 2 months. Therefore, in this study, we investigated the potential issues that may arise from prolonged exposure through food mixed with Polypropylene black microplastic (PB-MP) for over a year. We divided our study into short, mid, and long-term periods to assess cytotoxicity through Glucose tolerance test, Insulin tolerance test, analysis of insulin and c-peptide levels, hanging, grip, treadmill, Y-maze and open field tests, Respiratory Exchange Ratio, Energy Expenditure, Activity, and body composition. Through this, we comprehensively examined potential issues related to mouse behavior, muscle, metabolism and other factors. After dissection, RNA sequencing was carried out to investigate the effects on genes. For further verification, RT-qPCR was conducted. To summarize, our study provides evidence suggesting that treatment of microplastics for a short term has adverse effects, but with prolonged exposure, their effects tend to diminish.
Project description:Microplastics are defined as plastics ranging in size from 0.1μm to 5mm. Currently, research is being conducted across various fields to examine the effects of microplastics. Some studies demonstrated negative impacts on cells and mice. However, there is a lack of research on the effects by long-term exposure to microplastics. Most of the papers evaluated cytotoxicity with period of less than 2 months. Therefore, in this study, we investigated the potential issues that may arise from prolonged exposure through food mixed with Polypropylene microplastic (PP-MP) for over a year. We divided our study into short, mid, and long-term periods to assess cytotoxicity through Glucose tolerance test, Insulin tolerance test, analysis of insulin and c-peptide levels, hanging, grip, treadmill, Y-maze and open field tests, Respiratory Exchange Ratio, Energy Expenditure, Activity, and body composition. Through this, we comprehensively examined potential issues related to mouse behavior, muscle, metabolism and other factors. After dissection, RNA sequencing was carried out to investigate the effects on genes. For further verification, RT-qPCR was conducted. To summarize, our study provides evidence suggesting that treatment of microplastics for a short term has adverse effects, but with prolonged exposure, their effects tend to diminish.
Project description:Human skin colour, ie pigmentation, differs widely among individuals, as do their responses to various types of ultraviolet radiation (UV) and their risks of skin cancer. In some individuals, UV-induced pigmentation persists for months to years in a phenomenon termed long-lasting pigmentation (LLP). It is unclear whether LLP is an indicator of potential risk for skin cancer. LLP seems to have similar features to other forms of hyperpigmentation, eg solar lentigines or age spots, which are clinical markers of photodamage and risk factors for precancerous lesions. To investigate what UV-induced molecular changes may persist in individuals with LLP, clinical specimens from non-sunburn-inducing repeated UV exposures (UVA, UVB or UVA + UVB) at 4 months post-exposure (short-term LLP) were evaluated by microarray analysis and dataset mining. Validated targets were further evaluated in clinical specimens from six healthy individuals (three LLP+ and three LLP-) followed for more than 9 months (long-term LLP) who initially received a single sunburn-inducing UVA + UVB exposure. The results support a UV-induced hyperpigmentation model in which basal keratinocytes have an impaired ability to remove melanin that leads to a compensatory mechanism by neighbouring keratinocytes with increased proliferative capacity to maintain skin homeostasis. The attenuated expression of SOX7 and other hemidesmosomal components (integrin α6β4 and plectin) leads to increased melanosome uptake by keratinocytes and points to a spatial regulation within the epidermis. The reduced density of hemidesmosomes provides supporting evidence for plasticity at the epidermal-dermal junction. Altered hemidesmosome plasticity, and the sustained nature of LLP, may be mediated by the role of SOX7 in basal keratinocytes. The long-term sustained subtle changes detected are modest, but sufficient to create dramatic visual differences in skin colour. These results suggest that the hyperpigmentation phenomenon leading to increased interdigitation develops in order to maintain normal skin homeostasis in individuals with LLP.
Project description:BackgroundOpiate addiction reflects plastic changes that endurably alter synaptic transmission within relevant neuronal circuits. The biochemical mechanisms of these adaptations remain largely unknown and proteomics-based approaches could lead to a broad characterization of the molecular events underlying adaptations to chronic drug exposure.ResultsThus, we have started proteomic analyses of the effects of chronic morphine exposure in a recombinant human neuroblastoma SH-SY5Y clone that stably overexpresses the mu-opioid receptor. Cells were treated with morphine for 6, 24 and 72 hours, the proteins were separated by 2-D gel electrophoresis and stained with Coomassie blue, and the protein map was compared with that obtained from untreated cells. Spots showing a statistically significant variation were selected for identification using mass spectrometric analyses.ConclusionA total of 45 proteins were identified, including proteins involved in cellular metabolism, cytoskeleton organization, vesicular trafficking, transcriptional and translational regulation, and cell signaling.
Project description:The insulin/insulin-like growth factor-1 signalling (IIS) pathway regulates cellular and organismal metabolism and controls the rate of aging. Gain-of-function mutations in p110α, the principal mammalian IIS-responsive isoform of PI 3-kinase (PI3K), promote cancer. In contrast, loss-of-function mutations in p110α impair insulin signalling and cause insulin resistance, inducing a pre-diabetic state. It remains unknown if long-term p110α inactivation induces further metabolic deterioration over time, leading to overt unsustainable pathology. Surprisingly, we find that chronic p110α partial inactivation in mice protects from age-related reduction in insulin sensitivity, glucose tolerance and fat accumulation, and extends the lifespan of male mice. This beneficial effect of p110α inactivation derives in part from a suppressed down-regulation of insulin receptor substrate (IRS) protein levels induced by age-related hyperinsulinemia, and correlates with enhanced insulin-induced Akt signalling in aged p110α-deficient mice. This temporal metabolic plasticity upon p110α inactivation indicates that prolonged PI3K inhibition, as intended in human cancer treatment, might not negatively impact on organismal metabolism.
Project description:The negative impact of cigarette smoking on the skin includes accelerated aging, pigmentation disorders, and impaired wound healing, but its effect on the skin barrier is not completely understood. Here, we studied the changes in selected epidermal proteins and lipids between smokers (45-66 years, smoking > 10 years, > 10 cigarettes per day) and non-smokers. Volar forearm epidermal and stratum corneum samples, obtained by suction blister and tape stripping, respectively, showed increased thickness in smokers. In the epidermis of smokers, we observed a significant upregulation of filaggrin, loricrin, and a trend of increased involucrin but no differences were found in the case of transglutaminase 1 and kallikrein-related peptidase 7, on the gene and protein levels. No significant changes were observed in the major skin barrier lipids, except for increased cholesterol sulfate in smokers. Liquid chromatography coupled with mass spectrometry revealed shorter acyl chains in ceramides, and an increased proportion of sphingosine and 6-hydroxysphingosine ceramides (with C4 trans-double bond) over dihydrosphingosine and phytosphingosine ceramides in smokers, suggesting altered desaturase 1 activity. Smokers had more ordered lipid chains found by infrared spectroscopy. In conclusion, cigarette smoking perturbs the homeostasis of the barrier proteins and lipids even at a site not directly exposed to smoke.
Project description:Going into space is a disorienting experience. Many studies have looked at sensory functioning in space but the multisensory basis of orientation has not been systematically investigated. Here, we assess how prolonged exposure to microgravity affects the relative weighting of visual, gravity, and idiotropic cues to perceived orientation. We separated visual, body, and gravity (when present) cues to perceived orientation before, during, and after long-term exposure to microgravity during the missions of seven astronauts on the International Space Station (mean duration 168 days) and measuring perceived vertical using the subjective visual vertical and the perceptual upright. The relative influence of each cue and the variance of their judgments were measured. Fourteen ground-based control participants performed comparable measurements over a similar period. The variance of astronauts' subjective visual vertical judgments in the absence of visual cues was significantly larger immediately upon return to earth than before flight. Astronauts' perceptual upright demonstrated a reduced reliance on visual cues upon arrival on orbit that re-appeared long after returning to earth. For earth-bound controls, the contributions of body, gravity, and vision remained constant throughout the year-long testing period. This is the first multisensory study of orientation behavior in space and the first demonstration of long-term perceptual changes that persist after returning to earth. Astronauts showed a plasticity in the weighting of perceptual cues to orientation that could form the basis for future countermeasures.