Plastic pollution, which is one of the most important environmental problems at the present time, has been understood recently, and the effects of this pollution on ecosystem and biota are becoming a ...growing problem, especially in the aquatic ecosystems. Direct or indirect exposure to those particles leads to adverse effects on marine organisms. In the marine environment, plastic materials interact with other pollutants such as metals, thereby affecting the uptake levels of those pollutants in marine organisms. In the present study, the Manila clam Ruditapes philippinarum was exposed to polyethylene microbeads and mercury chloride in single, combined and incubated form at environmentally relative concentrations for one week in controlled laboratory conditions. The uptake and tissue distribution of both stressors as well as the vector role of microplastics on mercury uptake in the organisms were investigated. Filtration rates, biomarkers for immunomodulation and oxidative stress, and histological alterations were also evaluated. Microplastics were ingested by the clams, and translocated to the various tissues. However, contaminated microplastics displayed a negligible vector role in terms of mercury bioaccumulation in the clams. The single and interactive exposure of the stressors reduced the filtration rate in the clams. Both pollutants affected the immune system of the organisms. Histological alterations were determined in the gill and digestive gland tissues of the clams among the treatment groups, although oxidative stress biomarkers remained unchanged. This study suggests that the vector role of polyethylene microplastics in mercury uptake is negligible and reveals that the single and interactive one-week exposure of two pollutants induce toxicity in the manila clams.
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•Co-exposure decreased both Hg and MPs uptake compared to single exposure.•Hg bioaccumulation from PE surfaces was very low in Ruditapes philippinarum.•Environmentally relevant concentrations of MPs and Hg significantly reduced the filtration rates of manila clam.•Histological alterations were seen in manila clams after exposure.•Immunomodulation of R. philippinarum may be induced by MPs and Hg exposure.
Abstract
Objectives
Temozolomide (TMZ) is an effective drug for glioblastoma multiforme (GBM), but the mechanism underlying TMZ resistance is poorly understood. New evidence has revealed that the ...release of heat shock proteins (Hsps) derived from extracellular vesicles (EVs) play an important role in cancer progression by modulating tumor microenvironment and cellular cross-talk. This study aims to evaluate the effects of TMZ on the expression of EV-derived and cellular Hsps and cell motility in U87MG human glioblastoma cell line.
Methods
Glial-EVs were isolated from the culture medium and characterized by SEM and immunoblotting. The effect of TMZ treatments (25, 200 and 750 µM) on cell proliferation (MTT assay), migration (scratch assay), and Hsp60 and Hsp70 levels (immunoblotting) were evaluated.
Results
TMZ treatments led to an increase in intracellular Hsp70 while decreasing EV-derived Hsp70. Cellular Hsp60 level was elevated at the low dose of TMZ, but it reduced at higher TMZ concentrations. Hsp60 was also decreased in EVs secreted from TMZ-treated cells. Besides, TMZ treatment reduced the proliferation and migration of glioma cells in a dose-dependent manner.
Conclusions
Our results suggest that TMZ has the potential to target both EV-derived and cellular Hsps for GBM treatment, thus it may reduce cell motility.
Objective: Nigella sativa has been extensively investigated as an important potential agent for the healing of wounds and there have been numerous studies regarding its effect. Although thymoquinone ...(TQ) is a well-known active constituent of Nigella sativa, studies in to the usability of TQ on wound healing are still insufficient. In this study, we aimed to evaluate the in vitro wound healing potential of TQ. Materials and Methods: NIH/3T3 mouse embryonic fibroblast cells were used to evaluate the wound healing effect of TQ. Different concentrations of TQ (0.1, 1 and 10 microM) were applied to the cells and their cytotoxic effect on cells after 24- and 48- hours was measured by MTT assay. Its effect on wound healing after 18- and 24- hours recovery was examined by in vitro scratch assay. Also, the level of beta-catenin, an effective protein in the process of healing wounds, was determined by Western blot assay. Results: MTT analysis indicated that 0.1, 1 and 10 microM doses of TQ had increased the cell numbers. In vitro scratch assay data showed that treatment with 1 and 10 microM TQ resulted in a statistically significant wound closure activity (91.35% and 90.84%, respectively) compared to the control. Additionally, we observed a statistically significant increase in the beta-catenin protein level which supported our data. Conclusion: Our results demonstrated that TQ increases both the viability of NIH/3T3 cells and its wound closure activity in vitro, and that it has the effect of increasing crucial protein beta-catenin. This study suggests that TQ may be a valuable substance for the healing of wounds and that its usability should be investigated. Keywords: Thymoquinone, wound healing, NIH/3T3
Anesthetic-induced toxicity in early life may lead to risk of cognitive decline at later ages. Notably, multiple exposures to isoflurane (ISO) cause acute apoptotic cell death in the developing brain ...and long-term cognitive dysfunction. This study is the first to investigate whether levosimendan (LVS), known for its protective myocardial properties, can prevent anesthesia-induced apoptotic response in brain cells and learning and memory impairment. Postnatal day (P)7 Wistar albino pups were randomly assigned to groups consisting of an equal number of males and females in this laboratory investigation. We treated rats with LVS (0.8 mg/kg/day) intranasally 30 min before each ISO exposure (1.5%, 3 h) at P7+9+11. We selected DMSO as the drug vehicle. Also, the control group at P7+9+11 received 50% O
2
for 3 h instead of ISO. Neuroprotective activity of LVS against ISO-induced cognitive dysfunction was evaluated by Morris water maze. Expression of apoptotic-related proteins was detected in the whole brain using western blot. LVS pretreatment significantly prevented anesthesia-induced deficit in spatial learning (at P28-32) and memory (at P33, P60, and P90). No sex-dependent difference occurred on any day of the training and probe trial. Intranasal LVS was also found to significantly prevent the ISO-induced apoptosis by reducing Bax and cleaved caspase-3, and by increasing Bcl-2 and Bcl-xL. Our findings support pretreatment with intranasal LVS application as a simple strategy in daily clinical practice in pediatric anesthesia to protect infants and children from the risk of general anesthesia-induced cell death and cognitive declines.
In this study, the antifungal activity of cumin seed oil (CSO) was tested on
. (i) Minimum inhibitory concentrations (MICs) and related concentrations (IC
, IC
, and IC
) were detected; (ii) toxicity ...was evaluated by a water-soluble tetrazolium salt-1 (WST-1) assay; (iii) genomic/epigenomic alterations were evaluated by the coupled restriction enzyme digestion-random amplification (CRED-RA) method; (iv) oxidative stress was investigated by
expression, catalase activity, and DCF-DA staining; (v) deoxynivalenol biosynthesis was evaluated by
expression; (vi) and potential effects of CSO on wheat were tested by a water loss rate (WLR) assay. MIC, IC
, IC
and IC
values were detected at 0.5, 0.375, 0.25, and 0.125 mg mL
. In WST-1 assays, significant decreases (
< 0.001) were detected. Genomic template stability (GTS) related to methylation differences ranged from 94.60% to 96.30%. Percentage polymorphism for
II/
I values were as 9.1%/15.8%.
(oxidative stress-related catalase) and
(zinc finger motif transcription factor) gene expressions were recorded between 5.29 ± 0.74 and 0.46 ± 0.10 (
< 0.05). Increased catalase activity was detected (
< 0.05) by spectrophotometric assays. DCF-DA-stained (oxidative stressed) cells were increased in response to increased concentrations, and there were no significant changes in WLR values. It was concluded that CSO showed strong antifungal activity on
via different physiological levels.
Isoflurane is commonly used in pediatric population, but its mechanism of action in cognition is unclear. Aquaporin 4 (AQP4) regulates water content in blood, brain, and cerebrospinal fluid. Various ...studies have provided evidence for the role of AQP4 in synaptic plasticity and neurocognition. In this study, we aimed to determine whether a prolonged exposure to isoflurane in infant rats is associated with cognition and what effect this exposure has on AQP4 expression. Ten-day-old postnatal day (P) 10 Wistar albino rats were randomly allocated to isoflurane group (n = 32; 1.5% isoflurane in 50% oxygen for 6 hours) or control group (n = 32; only 50% oxygen for 6 hours). Acute (P11) and long-term (P33) effects of 6-hour anesthetic isoflurane exposure on AQP4 expression were analyzed in whole brains of P11 and P33 rats by RT-qPCR and Western blot. Spatial learning and memory were assessed on P28 to P33 days by Morris Water Maze (MWM) test. The analysis revealed that isoflurane increased acutely both mRNA (~4.5 fold) and protein (~90%) levels of AQP4 in P11 rats compared with control group. The increasing levels of AQP4 in P11 were not observed in P33 rats. Also, no statistically significant change between isoflurane and control groups was observed in the latency to find the platform during MWM training and probe trial. Our results indicate that a single exposure to isoflurane anesthesia does not influence cognition in infant rats. In this case, acutely increased AQP4 after isoflurane anesthesia may have a protective role in neurocognition.
The ability of Trolox (6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid), a water-soluble vitamin E analogue, to prevent oxidative damages is well characterized, but the mechanisms underlying ...it remain unclear. The protective effect of Trolox pre-treatment on H(2)O(2)-induced toxicity might be attributed to the decreased cellular permeability to H(2)O(2) or in vitro scavenging activity of Trolox, induction of antioxidant enzymes or the direct scavenging activity of Trolox. The results obtained rule out the first and second possibilities and intracellular scavenging activity was found to be the mechanism whereby Trolox confers protection. This was confirmed by measuring protein oxidation (levels), and the observed decrease in proteasomal activity indicated that the decrease in protein carbonyls was due to Trolox scavenging activity rather than proteasome activation. In conclusion, the intracellular scavenging activity of Trolox is a key protective mechanism against H(2)O(2). These findings obtained in Schizosaccharomyces pombe, a good model organism for eukaryotic cells, can be used as standard protocols for investigating the antioxidant activity of pure or complex potential antioxidants.
Microplastic (MP) toxicity has recently been explored in various marine species. Along with the toxicity of plastics polymer itself, additional substances or pollutants that are absorbed onto it may ...also be harmful. In the present study, we investigated the combined impacts of polyethylene microplastics (PE MPs) and an organic pollutant (Benzo(a)anthracene, BaA) on Manila clam Ruditapes philippinarum during a one-week exposure. Two PE MPs concentrations (26 μg L−1 and 260 μg L−1) and one BaA concentration (3 μg L−1) were tested. The clams were exposed to BaA and PE MPs either alone or in combination. BaA and PE MPs were incubated before the combined exposure. The biological effects of PE MPs and BaA on the clams were evaluated by considering several assays such as feeding rate, anti-oxidant enzyme activities, and the expression levels of stress-related genes. The feeding rate significantly decreased in individual PE MPs and individual BaA groups while it remained unchanged in combined groups. Superoxide dismutase (SOD) was the most affected among the biochemical parameters. Malondialdehyde (MDA), and glutathione peroxidase (GPx) activities were slightly affected, whereas no changes were observed in glutathione s-transferase (GST) activities. CYP1A1, CYP3A4, and HSP70 gene expressions displayed slightly significant changes. Considering all stressor groups, high PE MPs exposure (260 μg L−1 PE MPs) more effectively altered the biological parameters in the clams compared to individual low PE MPs and BaA exposure, and their combination. The results also indicated the negligible vector role of PE MPs to transport BaA into the clam tissues.
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•The feeding rate of clams substantially declined by polyethylene MP and Benzo(a)anthracene exposure.•The exposure of polyethylene MP and BaA influenced SOD, MDA and GPx activities bot not GST.•The regulation of genes HSP70, CYP1A1 and CYP3A4 were affected by polyethylene MP and BaA exposure.•BaA efficiently accumulated in clam tissues.•Polyethylene MP has a negligible vector role in transporting BaA to clams.
In this study, the antifungal activity of cumin seed oil (CSO) was tested on Fusarium graminearum . (i) Minimum inhibitory concentrations (MICs) and related concentrations (ICsub.75 , ICsub.50 , and ...ICsub.25 ) were detected; (ii) toxicity was evaluated by a water-soluble tetrazolium salt-1 (WST-1) assay; (iii) genomic/epigenomic alterations were evaluated by the coupled restriction enzyme digestion-random amplification (CRED-RA) method; (iv) oxidative stress was investigated by CAT expression, catalase activity, and DCF-DA staining; (v) deoxynivalenol biosynthesis was evaluated by tri6 expression; (vi) and potential effects of CSO on wheat were tested by a water loss rate (WLR) assay. MIC, ICsub.75 , ICsub.50 and ICsub.25 values were detected at 0.5, 0.375, 0.25, and 0.125 mg mLsup.−1 . In WST-1 assays, significant decreases (p < 0.001) were detected. Genomic template stability (GTS) related to methylation differences ranged from 94.60% to 96.30%. Percentage polymorphism for Hap II/Msp I values were as 9.1%/15.8%. CAT (oxidative stress-related catalase) and tri6 (zinc finger motif transcription factor) gene expressions were recorded between 5.29 ± 0.74 and 0.46 ± 0.10 (p < 0.05). Increased catalase activity was detected (p < 0.05) by spectrophotometric assays. DCF-DA-stained (oxidative stressed) cells were increased in response to increased concentrations, and there were no significant changes in WLR values. It was concluded that CSO showed strong antifungal activity on F. graminearum via different physiological levels.
Classical galactosemia is caused by a nearly complete deficiency of galactose-1-phosphate uridyltransferase (GALT; EC 2.7.712), resulting in a severely impaired galactose metabolism with ...galactose-1-phosphate and galactitol accumulation. Even on a galactose-restricted diet, patients develop serious long-term complications of the central nervous system and ovaries that may result from chronic cell-toxic effects exerted by endogenous galactose. To address the question of whether disease-associated cellular perturbations could affect the kidney function of the patients, we performed differential proteomics of detergent-resistant membranes from urinary exovesicles. Galactosemic samples (showing drastic shifts from high-mannose to complex-type N-glycosylation on exosomal N-glycoproteins) and healthy, sex-matched controls were analyzed in quadruplex iTRAQ experiments performed in biological and technical replicates. Particularly in the female patient group, the most striking finding was a drastic increase of abundant serum (glyco)proteins, like albumin, leucine-rich α-2-glycoprotein, fetuin, immunoglobulins, prostaglandin H2 d-isomerase, and α-1-microglobulin protein (AMBP), pointing to a subclinical failure of kidney filter function in galactosemic patients and resulting in a heavy overload of exosomal membranes with adsorbed serum (glyco)proteins. Several of these proteins are connected to TBMN and IgAN, proteinuria, and renal damage. The impairment of renal protein filtration was also indicated by increased protein contents derived from extracellular matrices and lysosomes.
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