Metabolic alterations and mitochondrial dysfunction in human airway BEAS-2B cells exposed to vanadium pentoxide.

Vanadium pentoxide (V+5) is a hazardous material that has drawn considerable attention due to its wide use in industrial sectors and increased release into environment from human activities. It poses potential adverse effects on animals and human health, with pronounced impact on lung physiology and functions. In this study, we investigated the metabolic response of human bronchial epithelial BEAS-2B cells to low-level V+5 exposure (0.01, 0.1, and 1 ppm) using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Exposure to V+5 caused extensive changes to cellular metabolism in BEAS-2B cells, including TCA cycle, glycolysis, fatty acids, amino acids, amino sugars, nucleotide sugar, sialic acid, vitamin D3, and drug metabolism, without causing cell death. Altered mitochondrial structure and function were observed with as low as 0.01 ppm (0.2 µM) V+5 exposure. In addition, decreased level of E-cadherin, the prototypical epithelial marker of epithelial-mesenchymal transition (EMT), was observed following V+5 treatment, supporting potential toxicity of V+5 at low levels. Taken together, the present study shows that V+5 has adverse effects on mitochondria and the metabolome which may result in EMT activation in the absence of cell death. Furthermore, results suggest that high-resolution metabolomics could serve as a powerful tool to investigate metal toxicity at levels which do not cause cell death.

Real-Time Exposure to 3D-Printing Emissions Elicits Metabolic and Pro-Inflammatory Responses in Human Airway Epithelial Cells.

Three-dimensional (3D) printer usage in household and school settings has raised health concerns regarding chemical and particle emission exposures during operation. Although the composition of 3D printer emissions varies depending on printer settings and materials, little is known about the impact that emissions from different filament types may have on respiratory health and underlying cellular mechanisms. In this study, we used an in vitro exposure chamber system to deliver emissions from two popular 3D-printing filament types, acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA), directly to human small airway epithelial cells (SAEC) cultured in an air-liquid interface during 3D printer operation. Using a scanning mobility particle sizer (SMPS) and an optical particle sizer (OPS), we monitored 3D printer particulate matter (PM) emissions in terms of their particle size distribution, concentrations, and calculated deposited doses. Elemental composition of ABS and PLA emissions was assessed using scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX). Finally, we compared the effects of emission exposure on cell viability, inflammation, and metabolism in SAEC. Our results reveal that, although ABS filaments emitted a higher total concentration of particles and PLA filaments emitted a higher concentration of smaller particles, SAEC were exposed to similar deposited doses of particles for each filament type. Conversely, ABS and PLA emissions had distinct elemental compositions, which were likely responsible for differential effects on SAEC viability, oxidative stress, release of inflammatory mediators, and changes in cellular metabolism. Specifically, while ABS- and PLA-emitted particles both reduced cellular viability and total glutathione levels in SAEC, ABS emissions had a significantly greater effect on glutathione relative to PLA emissions. Additionally, pro-inflammatory cytokines including IL-1ß, MMP-9, and RANTES were significantly increased due to ABS emissions exposure. While IL-6 and IL-8 were stimulated in both exposure scenarios, VEGF was exclusively increased due to PLA emissions exposures. Notably, ABS emissions induced metabolic perturbation on amino acids and energy metabolism, as well as redox-regulated pathways including arginine, methionine, cysteine, and vitamin B3 metabolism, whereas PLA emissions exposures caused fatty acid and carnitine dysregulation. Taken together, these results advance our mechanistic understanding of 3D-printer-emissions-induced respiratory toxicity and highlight the role that filament emission properties may play in mediating different respiratory outcomes.

Metabolic reprograming and increased inflammation by cadmium exposure following early-life respiratory syncytial virus infection-the involvement of protein S-palmitoylation.

Early-life respiratory syncytial virus (RSV) infection (eRSV) is one of the leading causes of serious pulmonary disease in children. eRSV is associated with higher risk of developing asthma and compromised lung function later in life. Cadmium (Cd) is a toxic metal, widely present in the environment and in food. We recently showed that eRSV re-programs metabolism and potentiates Cd toxicity in the lung, and our transcriptome-metabolome-wide study showed strong associations between S-palmitoyl transferase expression and Cd-stimulated lung inflammation and fibrosis signaling. Limited information is available on the mechanism by which eRSV re-programs metabolism and potentiates Cd toxicity in the lung. In the current study, we used a mouse model to examine the role of protein S-palmitoylation (Pr-S-Pal) in low dose Cd-elevated lung metabolic disruption and inflammation following eRSV. Mice exposed to eRSV were later treated with Cd (3.3 mg CdCl2/L) in drinking water for 6 weeks (RSV+Cd). The role of Pr-S-Pal was studied using a palmitoyl transferase inhibitor, 2-bromopalmitate (BP, 10 µM). Inflammatory marker analysis showed that cytokines, chemokines and inflammatory cells were highest in the RSV+Cd group, and BP decreased inflammatory markers. Lung metabolomics analysis showed that pathways including phenylalanine, tyrosine and tryptophan, phosphatidylinositol and sphingolipid were altered across treatments. BP antagonized metabolic disruption of sphingolipid and glycosaminoglycan metabolism by RSV+Cd, consistent with BP effect on inflammatory markers. This study shows that Cd exposure following eRSV has a significant impact on subsequent inflammatory response and lung metabolism, which is mediated by Pr-S-Pal, and warrants future research for a therapeutic target.

Low-dose vanadium pentoxide perturbed lung metabolism associated with inflammation and fibrosis signaling in male animal and in vitro models.

Vanadium is available as a dietary supplement and also is known to be toxic if inhaled, yet little information is available concerning the effects of vanadium on mammalian metabolism when concentrations found in food and water. Vanadium pentoxide (V+5) is representative of the most common dietary and environmental exposures, and prior research shows that low-dose V+5 exposure causes oxidative stress measured by glutathione oxidation and protein S-glutathionylation. We examined the metabolic impact of V+5 at relevant dietary and environmental doses (0.01, 0.1, and 1 ppm for 24 h) in human lung fibroblasts (HLFs) and male C57BL/6J mice (0.02, 0.2, and 2 ppm in drinking water for 7 mo). Untargeted metabolomics using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) showed that V+5 induced significant metabolic perturbations in both HLF cells and mouse lungs. We noted 30% of the significantly altered pathways in HLF cells, including pyrimidines and aminosugars, fatty acids, mitochondrial and redox pathways, showed similar dose-dependent patterns in mouse lung tissues. Alterations in lipid metabolism included leukotrienes and prostaglandins involved in inflammatory signaling, which have been associated with the pathogenesis of idiopathic pulmonary fibrosis (IPF) and other disease processes. Elevated hydroxyproline levels and excessive collagen deposition were also present in lungs from V+5-treated mice. Taken together, these results show that oxidative stress from environmental V+5, ingested at low levels, could alter metabolism to contribute to common human lung diseases.NEW & NOTEWORTHY We used relevant dietary and environmental doses of Vanadium pentoxide (V+5) to examine its metabolic impact in vitro and in vivo. Using liquid chromatography-high-resolution mass spectrometry (LC-HRMS), we found significant metabolic perturbations, with similar dose-dependent patterns observed in human lung fibroblasts and male mouse lungs. Alterations in lipid metabolism included inflammatory signaling, elevated hydroxyproline levels, and excessive collagen deposition were present in V+5-treated lungs. Our findings suggest that low levels of V+5 could trigger pulmonary fibrotic signaling.

Study on the relationship between selenium and cadmium in diseased human lungs.

Cadmium (Cd) is a toxic environmental metal that interacts with selenium (Se) and contributes to many lung diseases. Humans have widespread exposures to Cd through diet and cigarette smoking, and studies in rodent models show that Se can protect against Cd toxicities. We sought to identify whether an antagonistic relationship existed between Se and Cd burdens and determine whether this relationship may associate with metabolic variation within human lungs. We performed metabolomics of 31 human lungs, including 25 with end-stage lung disease due to idiopathic pulmonary fibrosis, cystic fibrosis, chronic obstructive lung disease (COPD)/emphysema and other causes, and 6 non-diseased lungs. Results showed pathway associations with Cd including amino acid, lipid and energy-related pathways. Metabolic pathways varying with Se had considerable overlap with these pathways. Hierarchical cluster analysis (HCA) of individuals according to metabolites associated with Cd showed partial separation of disease types, with COPD/emphysema in the cluster with highest Cd, and non-diseased lungs in the cluster with the lowest Cd. When compared to HCA of metabolites associated with Se, the results showed that the cluster containing COPD/emphysema had the lowest Se, and the non-diseased lungs had the highest Se. A greater number of pathway associations occurred for Cd to Se ratio than either Cd or Se alone, indicating that metabolic patterns were more dependent on Cd to Se ratio than on either alone. Network analysis of interactions of Cd and Se showed network centrality was associated with pathways linked to polyunsaturated fatty acids involved in inflammatory signaling. Overall, the data show that metabolic pathway responses in human lung vary with Cd and Se in a pattern suggesting that Se is antagonistic to Cd toxicity in humans.

Metabolomics of V2O5 nanoparticles and V2O5 nanofibers in human airway epithelial BEAS-2B cells.

Vanadium is a toxic metal listed by the IARC as possibly carcinogenic to humans. Manufactured nanosize vanadium pentoxide (V2O5) materials are used in a wide range of industrial sectors and recently have been developed as nanomedicine for cancer therapeutics, yet limited information is available to evaluate relevant nanotoxicity. In this study we used high-resolution metabolomics to assess effects of two V2O5 nanomaterials, nanoparticles and nanofibers, at exposure levels (0.01, 0.1, and 1 ppm) that did not cause cell death (i.e., non-cytotoxic) in a human airway epithelial cell line, BEAS-2B. As prepared, V2O5 nanofiber exhibited a fibrous morphology, with a width approximately 63 ± 12 nm and length in average 420 ± 70 nm; whereas, V2O5 nanoparticles showed a typical particle morphology with a size 36 ± 2 nm. Both V2O5 nanoparticles and nanofibers had dose-response effects on aminosugar, amino acid, fatty acid, carnitine, niacin and nucleotide metabolism. Differential effects of the particles and fibers included dibasic acid, glycosphingolipid and glycerophospholipid pathway associations with V2O5 nanoparticles, and cholesterol and sialic acid metabolism associations with V2O5 nanofibers. Examination by transmission electron microscopy provided evidence for mitochondrial stress and increased lysosome fusion by both nanomaterials, and these data were supported by effects on mitochondrial membrane potential and lysosomal activity. The results showed that non-cytotoxic exposures to V2O5 nanomaterials impact major metabolic pathways previously associated with human lung diseases and suggest that toxico-metabolomics may be useful to evaluate health risks from V2O5 nanomaterials.

Vanadium pentoxide induced oxidative stress and cellular senescence in human lung fibroblasts.

Both environmental exposure to vanadium pentoxide (V2O5, V+5 for its ionic counterparts) and fibroblast senescence are associated with pulmonary fibrosis, but whether V+5 causes fibroblast senescence remains unknown. We found in a dose-response study that 2-40 µM V+5 caused human lung fibroblasts (HLF) senescence with increased senescence-associated ß-galactosidase activity and p16 expression, while cell death occurred at higher concentration (LC50, 82 µM V+5). Notably, measures of reactive oxygen species (ROS) production with fluorescence probes showed no association of ROS with V+5-dependent senescence. Preloading catalase (polyethylene-conjugated), a H2O2 scavenger, did not alleviate the cellular senescence induced by V+5. Analyses of the cellular glutathione (GSH) system showed that V+5 oxidized GSH, increased GSH biosynthesis, stimulated cellular GSH efflux and increased protein S-glutathionylation, and addition of N-acetyl cysteine inhibited V+5-elevated p16 expression, suggesting that thiol oxidation mediates V+5-caused senescence. Moreover, strong correlations between GSSG/GSH redox potential (Eh), protein S-glutathionylation, and cellular senescence (R2 > 0.99, p < 0.05) were present in V+5-treated cells. Studies with cell-free and enzyme-free solutions showed that V+5 directly oxidized GSH with formation of V+4 and GSSG in the absence of O2. Analyses of V+5 and V+4 in HLF and culture media showed that V+5 was reduced to V+4 in cells and that a stable V+4/V+5 ratio was rapidly achieved in extracellular media, indicating ongoing release of V+4 and reoxidation to V+5. Together, the results show that V+5-dependent fibroblast senescence is associated with a cellular/extracellular redox cycling mechanism involving the GSH system and occurring under conditions that do not cause cell death. These results establish a mechanism by which environmental vanadium from food, dietary supplements or drinking water, can cause or contribute to lung fibrosis in the absence of high-level occupational exposures and cytotoxic cell death.

Low-Dose Cadmium Potentiates Metabolic Reprogramming Following Early-Life Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) infection causes serious pulmonary disease and death in high-risk infants and elderly. Cadmium (Cd) is a toxic environmental metal contaminant and constantly exposed to humans. Limited information is available on Cd toxicity after early-life respiratory virus infection. In this study, we examined the effects of low-dose Cd exposure following early-life RSV infection on lung metabolism and inflammation using mouse and fibroblast culture models. C57BL/6J mice at 8 days old were exposed to RSV 2 times with a 4-week interval. A subset of RSV-infected mice was subsequently treated with Cd at a low dose in drinking water (RSV infection at infant age [RSVinf]+Cd) for 16 weeks. The results of inflammatory marker analysis showed that the levels of cytokines and chemokines were substantially higher in RSVinf+Cd group than other groups, implying that low-dose Cd following early-life RSV infection enhanced lung inflammation. Moreover, histopathology data showed that inflammatory cells and thickening of the alveolar walls as a profibrotic signature were evident in RSVinf+Cd. The metabolomics data revealed that RSVinf+Cd-caused metabolic disruption in histamine and histidine, vitamin D and urea cycle, and pyrimidine pathway accompanying with mechanistic target of rapamycin complex-1 activation. Taken together, our study demonstrates for the first time that cumulative Cd exposure following early-life RSV infection has a significant impact on subsequent inflammation and lung metabolism. Thus, early-life respiratory infection may reprogram metabolism and potentiate Cd toxicity, enhance inflammation, and cause fibrosis later in life.

Health-Promoting Phenolic Compound Accumulation, Antioxidant Response, Endogenous Salicylic Acid Generation, and Biosynthesis Gene Expression in Germinated Pigeon Pea Seeds Treated with UV-B Radiation.

Germinated pigeon pea seeds (GPPSs) are good dietary supplements with satisfactory nutritional and medicinal values. In this study, UV-B treatment was used to promote the accumulation of health-promoting phenolic compounds (10 flavonoids and 1 stilbene) in GPPS. The total yield of 11 phenolic compounds (235 839.76 ± 17 118.24 ng/g DW) significantly improved (2.53-fold increase) in GPPSs exposed to UV-B radiation (3 W/m2) for 8 h, whereas free amino acid and reducing sugar contents exhibited a decreasing tendency during UV-B exposure. Meanwhile, the positive response in the antioxidant activities of enzymes and nonenzymatic extracts was noticed in UV-B-treated GPPSs. Moreover, UV-B radiation could cause tissue damages in hypocotyls and cotyledons of the GPPSs and enhance the generation of endogenous salicylic acid, thus activating the expression of biosynthesis genes (especially CHS and STS1). Overall, the simple UV-B supplementation strategy makes GPPSs more attractive as functional foods/nutraceuticals in diet for promoting human health.

Firsthand and Secondhand Exposure Levels of Maltol-Flavored Electronic Nicotine Delivery System Vapors Disrupt Amino Acid Metabolism.

Electronic nicotine delivery system (ENDS) use has become a popular, generally regarded as safe, alternative to tobacco use. The e-liquids used for ENDS vapor generation commonly contain flavoring agents, such as maltol, which have been subjected to little investigation of their effects on lung health from ENDS usage. In the present study, we examined the impacts of firsthand (3.9 mM) and secondhand (3.9 µM) exposure levels to maltol-flavored ENDS vapors on lung metabolism. Human lung bronchial epithelial cells were exposed to ENDS vapors using a robotic system for controlled generation and delivery of exposures, and the effects on metabolism were evaluated using high-resolution metabolomics. The results show that maltol in e-liquids impacts lung airway epithelial cell metabolism at both firsthand and secondhand exposure levels. The effects of maltol were most notably seen in amino acid metabolism while oxidative stress was observed with exposure to all ENDS vapors including e-liquids alone and maltol-contained e-liquids. Many effects of firsthand exposure were also observed with secondhand exposure, suggesting need for systematic investigation of both firsthand and secondhand effects of flavored ENDS vapors on lung metabolism and risk of lung disease.

Defense Mechanisms of Two Pioneer Submerged Plants during Their Optimal Performance Period in the Bioaccumulation of Lead: A Comparative Study.

Ceratophyllum demersum L. and Hydrilla verticillata (L.f.) Royle, two pioneer, submerged plants, effectively remove heavy metals from contaminated water. The present work evaluates the bioaccumulation and defense mechanisms of these plants in the accumulation of lead from contaminated water during their optimal performance period. C. demersum and H. verticillata were investigated after 14 days of exposure to various lead concentrations (5⁻80 µM). The lead accumulation in both C. demersum and H. verticillata increased with an increasing lead concentration, reaching maximum values of 2462.7 and 1792 mg kg-1 dw, respectively, at 80 µM. The biomass and protein content decreased significantly in C. demersum when exposed to lead. The biomass of H. verticillata exposed to lead had no significant difference from that of the controls, and the protein content increased for the 5⁻10 µM exposure groups. The malondialdehyde (MDA) content and superoxide dismutase (SOD), peroxidase (POD), and polyphenol oxidase (PPO) activities were much higher in C. demersum, suggesting considerable damage from lipid peroxidation and sensitivity to lead stress. Enzyme inhibition and inactivation were also observed in C. demersum at high lead concentrations (40⁻80 µM). The excellent growth status, low damage from lipid peroxidation, and high activity of catalase (CAT) and phenylalanine ammonia-lyase (PAL) observed in H. verticillata illustrate its better tolerance under the same lead stress.

High-potential accumulation and tolerance in the submerged hydrophyte Hydrilla verticillata (L.f.) Royle for nickel-contaminated water.

Water contamination by nickel (Ni) has become an increasing concern in recent decades. Hydrilla verticillata (L.f.) Royle has been recognized as a promising accumulator of several potentially toxic elements (PTEs) in phytoremediation, but its Ni-accumulation characteristics and its mechanisms of tolerance to Ni remain largely unknown. This research investigated the biochemical responses of leaves and stems of H. verticillata to various concentrations of Ni (5, 10, 15, 20, and 40 µM) over periods of 7, 14, or 21 days. Plants accumulated considerable Ni to a maximum amount of 1080 mg kg-1 dry weight (DW) with a maximum bioconcentration factor of 1100; thus, high Ni accumulation was detected in H. verticillata. Low concentrations (5-15 µM) or short durations (less than 14 days) of Ni exposure might promote plant growth without adversely affecting normal metabolism. After peaking at day 14, a decline in bioaccumulation was unexpectedly observed as a long-term effect of Ni toxicity. Malondialdehyde content and the activities of defense-related enzymes changed in a similar pattern after treatment with Ni, increasing with both Ni concentration and exposure time to a peak (often at 5-15 µM on day 14), followed by a decline. Through a comprehensive analysis of all the test parameters, the tolerance thresholds were determined to be > 40.0 µM, 24.0 µM, and 15.8 µM at days 7, 14, and 21, respectively. Hydrilla verticillata could be a "high-potential accumulator" capable of decontaminating aquatic bodies polluted by Ni within the threshold range.

Toxicity of engineered nanomaterials mediated by nano-bio-eco interactions.

Engineered nanomaterials may adversely impact human health and environmental safety by nano-bio-eco interactions not fully understood. Their interaction with biotic and abiotic environments are varied and complicated, ranging from individual species to entire ecosystems. Their behavior, transport, fate, and toxicological profiles in these interactions, addressed in a pioneering study, are subsequently seldom reported. Biological, chemical, and physical dimension properties, the so-called multidimensional characterization, determine interactions. Intermediate species generated in the dynamic process of nanomaterial transformation increase the complexity of assessing nanotoxicity. We review recent progress in understanding these interactions, discuss the challenges of the study, and suggest future research directions.

Transcriptomic Response of Chinese Yew (Taxus chinensis) to Cold Stress.

Taxus chinensis is a rare and endangered shrub, highly sensitive to temperature changes and widely known for its potential in cancer treatment. How gene expression of T. chinensis responds to low temperature is still unknown. To investigate cold response of the genus Taxus, we obtained the transcriptome profiles of T. chinensis grown under normal and low temperature (cold stress, 0°C) conditions using Illumina Miseq sequencing. A transcriptome including 83,963 transcripts and 62,654 genes were assembled from 4.16 Gb of reads data. Comparative transcriptomic analysis identified 2,025 differently expressed (DE) isoforms at p < 0.05, of which 1,437 were up-regulated by cold stress and 588 were down-regulated. Annotation of DE isoforms indicated that transcription factors (TFs) in the MAPK signaling pathway and TF families of NAC, WRKY, bZIP, MYB, and ERF were transcriptionally activated. This might have been caused by the accumulation of secondary messengers, such as reactive oxygen species (ROS) and Ca2+. While accumulation of ROS will have caused damages to cells, our results indicated that to adapt to low temperatures T. chinensis employed a series of mechanisms to minimize these damages. The mechanisms included: (i) cold-enhanced expression of ROS deoxidant systems, such as peroxidase and phospholipid hydroperoxide glutathione peroxidase, to remove ROS. This was further confirmed by analyses showing increased activity of POD, SOD, and CAT under cold stress. (ii) Activation of starch and sucrose metabolism, thiamine metabolism, and purine metabolism by cold-stress to produce metabolites which either protect cell organelles or lower the ROS content in cells. These processes are regulated by ROS signaling, as the "feedback" toward ROS accumulation.

N-(3-oxo-hexanoyl)-homoserine lactone has a critical contribution to the quorum-sensing-dependent regulation in phytopathogen Pseudomonas syringae pv. tabaci 11528.

The phytopathogen Pseudomonas syringae pv. tabaci 11528 (P. syringae 11528), causing wild-fire disease in soybean and tobacco plants, processes PsyI-PsyR quorum-sensing (QS) system, in which PsyI is the N-(3-oxo-hexanoyl)-homoserine lactone (3OC6-HSL) synthase. In comparison to P. syringae 11528 AHL-deficient mutant, 845 3OC6-HSL-dependent genes were identified using RNA sequencing (RNA-seq) in the AHL-deficient mutant grown with exogenous 3OC6-HSL in the transition from the exponential to the stationary phase, and many of them were associated with virulence, which were negatively regulated. The gene ontology and KEGG pathway enrichment analysis of those genes presented that the most pronounced regulation was involved in bacterial motility. Moreover, similar expression profiles of genes during growth phases were observed in both the wild type and the AHL-deficient mutant with exogenous 3OC6-HSL compared with the AHL-deficient mutant. These findings imply that 3OC6-HSL has a critical contribution to the QS-dependent regulation on gene expression, and 3OC6-HSL-dependent regulation may play a significant role in plant infection.

Bioaccumulation and tolerance characteristics of a submerged plant (Ceratophyllum demersum L.) exposed to toxic metal lead.

A hydroponic study was conducted to investigate the lead bioaccumulation and tolerance characteristics of Ceratophyllum demersum L. exposed to various lead concentrations (5-80 µM) for 7, 14 or 21 days. Lead accumulation increased with increasing concentrations of metal in the solution, to a maximum accumulation of 4016.4 mg kg(-1) dw. Unexpectedly, the release of accumulated lead from the plants into solution was observed for all experimental groups except those exposed to 5 µM. Both the biomass and protein content of the plants responded significantly to lead stress. Malondialdehyde (MDA) levels increased substantially at lead concentrations below 20 µM, further indicating that this metal is toxic to the plants. To reveal the mechanism underlying the defense against lead stress, plants were also assayed for the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD), as well as other relevant enzymes such as phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO). The activities of both SOD and CAT increased at lower lead concentrations and with shorter exposure times, followed by a decline, but the activities of POD and its isoenzymes continued to increase under all conditions. Moreover, increases in the activities of PAL and PPO were observed only for the 14-day treatment, and these two enzymes were not sensitive to lead concentration. These results suggest that C. demersum exhibits strong tolerance within a specific concentration range of lead in solution; according to regression analysis, 40 µM is suggested to be this plant's tolerance threshold for lead in water. Furthermore, the malfunction of this tolerance mechanism might accelerate the metal-release process. These attributes are likely to be beneficial for utilizing C. demersum in phytoremediation applications.

Metal Oxide Nanomaterials in Nanomedicine: Applications in Photodynamic Therapy and Potential Toxicity.

Metal oxide nanomaterials have exhibited excellent performance as nanomedicines in photodynamic therapy (PDT) for cancer and infection treatment. Their unique and tunable physicochemical properties advance them as promising alternatives in drug delivery, early diagnosis, imaging, and treatment against various tumors and infectious diseases. Moreover, the implementation of nanophototherapy in deep tissue sites is enhanced by advancements in photosensitization technology. Notwithstanding the progress made in emerging metal oxide nanomaterials-derived PDT, the potential toxicity towards adjunct tissues associated with this approach remains challenging. Regulation and legislation have also been recommended and subsequently enacted in response to public concerns related to large-scale production, transportation, use, and disposal of those nanomaterials. Consequently, a quantitative structure-activity relationship (QSAR) paradigm has been adopted and is widely used in evaluating and predicting the side effects of nanomedicines, thus influencing their design and fabrication. This article briefly reviews the application of metal oxide nanomaterials in PDT and their associated adverse impacts as reported in recent publications. The future trends and implications of this platform in nanomedicine are also highlighted. However, more studies and efforts have to be carried out for developing novel nano-therapeutics with high selectivity, sensitivity, biocompatibility, and minimal side effects in PDT.

An in vivo study on the photo-enhanced toxicities of S-doped TiO2 nanoparticles to zebrafish embryos (Danio rerio) in terms of malformation, mortality, rheotaxis dysfunction, and DNA damage.

The role of light on the acute toxicities of S-doped and Sigma TiO2 nanoparticles in zebrafish was studied. Metrics included mortality for both, and rheotaxis dysfunction and DNA damage for S-doped only. It was found that the acute toxicity of S-TiO2 nanoparticles was enhanced by simulated sunlight (SSL) irradiation (96-h LC50 of 116.56 ppm) and exceeded that of Sigma TiO2, which was essentially non-toxic. Behavioral disorder, in terms of rheotaxis, was significantly increased by treatment with S-TiO2 nanoparticles under SSL irradiation. In order to further understand its toxicity mechanism, we investigated hair cells in neuromasts of the posterior lateral line (PLL) using DASPEI staining. Significant hair cell damage was observed in the treated larvae. The Comet assay was employed to investigate the DNA damage, which might be responsible for the loss of hair cells. Production of the superoxide anion ([Formula: see text]), a major ROS generated by TiO2 nanoparticles, was assayed and used to postulate causative factors to account for these damages. Oxidative effects were most severe in the liver, heart, intestine, pancreatic duct, and pancreatic islet - results consistent with our earlier findings in the investigation of embryonic malformation. TEM micrographs, used to further investigate the fate of S-TiO2 nanoparticles at the cellular level, suggested receptor-mediated autophagy and vacuolization. Our findings validate the benefit of using the transparent zebrafish embryo as an in vivo model for evaluating photo-induced nanotoxicity. These results highlight the importance of conducting a systematic risk assessment in connection with the use of doped TiO2 nanoparticles in aquatic ecosystems.