Subway station dust-induced pulmonary inflammation may be due to the dysfunction of alveolar macrophages: Possible contribution of bound elements.

With its increasing value as a means of public transportation, the health effects of the air in subway stations have attracted public concern. In the current study, we investigated the pulmonary toxicity of dust collected from an air purifier installed on the platform of the busiest subway station in Seoul. We found that the dust contained various elements which are attributable to the facilities and equipment used to operate the subway system. Particularly, iron (Fe), chromium (Cr), zirconium (Zr), barium (Ba), and molybdenum (Mo) levels were more notable in comparison with those in dust collected from the ventilation chamber of a subway station. To explore the health effects of inhaled dust, we first instilled via the trachea in ICR mice for 13 weeks. The total number of pulmonary macrophages increased significantly with the dose, accompanying hematological changes. Dust-laden alveolar macrophages and inflammatory cells accumulated in the perivascular regions in the lungs of the treated mice, and pulmonary levels of CXCL-1, TNF-α, and TGF-ß increased clearly compared with the control. The CCR5 and CD54 level expressed on BAL cell membranes was also enhanced following exposure to dust, whereas the CXCR2 level tended to decrease in the same samples. In addition, we treated the dust to alveolar macrophages (known as dust cells), lysosomal and mitochondrial function decreased, accompanied by cell death, and NO production was rapidly elevated with concentration. Moreover, the expression of autophagy- (p62) and anti-oxidant (SOD-2)-related proteins increased, and the expression of inflammation-related genes was dramatically up-regulated in the dust-treated cells. Therefore, we suggest that dysfunction of alveolar macrophages may importantly contribute to dust-induced inflammatory responses and that the exposure concentrations of Cr, Fe, Mo, Zr, and Ba should be considered carefully when assessing the health risks associated with subway dust. We also hypothesize that the bound elements may contribute to dust-induced macrophage dysfunction by inhibiting viability.

Subchronic pulmonary toxicity of ambient particles containing cement production-related elements.

Chronic respiratory disease is among the most common non-communicable diseases, and particulate materials (PM) are a major risk factor. Meanwhile, evidence of the relationship between the physicochemical characteristics of PM and pulmonary toxicity mechanism is still limited. Here, we collected particles (CPM) from the air of a port city adjacent to a cement factory, and we found that the CPM contained various elements, including heavy metals (such as arsenic, thallium, barium, and zirconium) which are predicted to have originated from a cement plant adjacent to the sampling site. We also delivered the CPM intratracheally to mice for 13 weeks to investigate the pulmonary toxicity of inhaled CPM. CPM-induced chronic inflammatory lesions with an increased total number of cells in the lung of mice. Meanwhile, among inflammatory mediators measured in this study, levels of IL-1ß, TNF-α, CXCL-1, and IFN-γ were elevated in the treated group compared with the controls. Considering that the alveolar macrophage (known as dust cell) is a professional phagocyte that is responsible for the clearance of PM from the respiratory surfaces, we also investigated cellular responses following exposure to CPM in MH-S cells, a mouse alveolar macrophage cell line. CPM inhibited cell proliferation and formed autophagosome-like vacuoles. Intracellular calcium accumulation and oxidative stress, and altered expression of pyrimidine metabolism- and olfactory transduction-related genes were observed in CPM-treated cells. More interestingly, type I-LC3B and full-length PARP proteins were not replenished in CPM-treated cells, and cell cycle changes, apoptotic and necrotic cell death, and caspase-3 cleavage were not significantly detected in cells exposed to CPM. Taken together, we conclude that dysfunction of alveolar macrophages may contribute to CPM-induced pulmonary inflammation. In addition, given the possible transformation of heart tissue observed in CPM-treated mice, we suggest that further study is needed to clarify the systemic pathological changes and the molecular mechanisms following chronic exposure to CPM.

Differential susceptibility to arsenic in glutathione S-transferase omega 2 (GST-O2)-targeted freshwater water flea Daphnia magna mutants.

To examine the role of glutathione S-transferase omega class (GST-O2) genes in the biotransformation and detoxification in Daphnia magna, various responses such as in vivo endpoints, arsenic speciation, enzymatic activities, and gene expression pathways related to arsenic metabolism were investigated in wild-type (WT) and GST-O2-mutant-type (MT) fleas produced by CRISPR/Cas9. Sensitivity to arsenic in MT fleas was higher than in WT fleas. Also, the reduction rate of arsenate (AsV) to arsenite (AsIII) in the MT group was significantly lower and led to accumulation of higher arsenic concentrations, resulting in decreased protection against arsenic toxicity. Relative mRNA expression of other GST genes in the GST-O2-targeted MT group generally increased but the enzymatic activity of GST decreased compared with the WT group. Oxidative stress on arsenic exposure was more strongly induced in the MT group compared with the WT group, resulting in a decrease in the ability to defend against toxicity in GST-O2-targeted mutant D. magna. Our results suggest that GST-O2 plays an important role in arsenic biotransformation and detoxification functions in D. magna.

Uptake and toxicity of cerium dioxide nanoparticles with different aspect ratio.

Cerium dioxide nanoparticles (CeONPs) have been extensively applied in research for future energy development due to two common oxidation states on their surface. Considering that shape (aspect ratio) is a key determinant of NPs-induced toxicity, we compared the toxicity of hexagonal (H)- and rod-shaped (R)-CeONPs in mice. At 24 h after pharyngeal aspiration, both types of CeONPs recruited surrounding immune cells (monocytes and neutrophils) into the lung, and R-CeONPs induced a more severe pulmonary inflammatory response compared with H-CeONPs. To identify an indicator to predict pulmonary inflammatory responses at the cellular level, we also investigated their responses in alveolar macrophage cells. At 24 h after treatment, both types of CeONPs were mainly located within the vacuoles (partially, in the lysosome) in the cytoplasm. Mitochondrial damage, intracellular calcium accumulation, and increased NO production were observed in cells exposed to both types of CeONPs, ultimately resulting in a decrease in cell viability. More interestingly, both types of CeONPs formed multinucleated giant cells. Meanwhile, contrary to when suspended in deionized water, R-CeONPs were strongly aggregated with a negative charge in cell culture media, whereas H-CeONPs were relatively well-dispersed with a positive charge. R-CeONPs-induced lysosomal extension was also recovered by premix with negatively charged DNA, and even NPs suspended in cell culture media without cells were detected under the FACS system, suggesting interference by protein corona. Therefore, we suggest that shape (aspect ratio) is an important factor determining inhaled NPs-induced pathology and that the effect of the surface charge and protein corona should be carefully considered in interpreting results derived from in vitro tests. Furthermore, we propose that the relationship between the formation of multinucleated giant cells and the inflammatory response of inhaled CeONPs should be further studied.

Silica-coated magnetic nanoparticles activate microglia and induce neurotoxic D-serine secretion.

BACKGROUND: Nanoparticles have been studied for brain imaging, diagnosis, and drug delivery owing to their versatile properties due to their small sizes. However, there are growing concerns that nanoparticles may exert toxic effects in the brain. In this study, we assessed direct nanotoxicity on microglia, the resident macrophages of the central nervous system, and indirect toxicity on neuronal cells exerted by silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)]. METHODS: We investigated MNPs@SiO2(RITC)-induced biological changes in BV2 murine microglial cells via RNA-sequencing-based transcriptome analysis and gas chromatography-mass spectrometry-based intracellular and extracellular amino acid profiling. Morphological changes were analyzed by transmission electron microscopy. Indirect effects of MNPs@SiO2(RITC) on neuronal cells were assessed by Transwell-based coculture with MNPs@SiO2(RITC)-treated microglia. MNPs@SiO2(RITC)-induced biological changes in the mouse brain in vivo were examined by immunohistochemical analysis. RESULTS: BV2 murine microglial cells were morphologically activated and the expression of Iba1, an activation marker protein, was increased after MNPs@SiO2(RITC) treatment. Transmission electron microscopy analysis revealed lysosomal accumulation of MNPs@SiO2(RITC) and the formation of vesicle-like structures in MNPs@SiO2(RITC)-treated BV2 cells. The expression of several genes related to metabolism and inflammation were altered in 100 µg/ml MNPs@SiO2(RITC)-treated microglia when compared with that in non-treated (control) and 10 µg/ml MNPs@SiO2(RITC)-treated microglia. Combined transcriptome and amino acid profiling analyses revealed that the transport of serine family amino acids, including glycine, cysteine, and serine, was enhanced. However, only serine was increased in the growth medium of activated microglia; especially, excitotoxic D-serine secretion from primary rat microglia was the most strongly enhanced. Activated primary microglia reduced intracellular ATP levels and proteasome activity in cocultured neuronal cells, especially in primary cortical neurons, via D-serine secretion. Moreover, ubiquitinated proteins accumulated and inclusion bodies were increased in primary dopaminergic and cortical neurons cocultured with activated primary microglia. In vivo, MNPs@SiO2(RITC), D-serine, and ubiquitin aggresomes were distributed in the MNPs@SiO2(RITC)-treated mouse brain. CONCLUSIONS: MNPs@SiO2(RITC)-induced activation of microglia triggers excitotoxicity in neurons via D-serine secretion, highlighting the importance of neurotoxicity mechanisms incurred by nanoparticle-induced microglial activation.

Toxicity mechanisms of arsenic compounds in aquatic organisms.

Arsenic is a toxic metalloid that is widely distributed in the environment due to its persistence and accumulative properties. The occurrence, distribution, and biological effects of arsenic in aquatic environments have been extensively studied. Acute and chronic toxicities to arsenic are associated with fatal effects at the individual and molecular levels. The toxicity of arsenic in aquatic organisms depends on its speciation and concentration. In aquatic environments, inorganic arsenic is the dominant form. While trivalent arsenicals have greater toxicity compared with pentavalent arsenicals, inorganic arsenic can assume a variety of forms through biotransformation in aquatic organisms. Biotransformation mechanisms and speciation of arsenic have been studied, but few reports have addressed the relationships among speciation, toxicity, and bioavailability in biological systems. This paper reviews the modes of action of arsenic along with its toxic effects and distribution in an attempt to improve our understanding of the mechanisms of arsenic toxicity in aquatic organisms.

Seawater contamination associated with in-water cleaning of ship hulls and the potential risk to the marine environment.

In-water cleaning can clear-off foulants from ship hulls to prevent transportation of non-indigenous species and reduce hull friction and consequent fuel use. However, during cleaning, antifouling paint residues containing toxic substances can be released into the environment. To understand the potential risks of in-water hull cleaning, cleaning effluents were collected and analyzed for total suspended solid (TSS), particle size distribution, and metal concentrations. TSS concentrations were 97.3-249 mg/L, corresponding to release rates of 12.9-37.5 g/m2 from the hull surface. Particles with sizes of ≥8 µm contributed 75-94% of the TSS. Average Cu and Zn concentrations in the effluents were 209 µg/L and 1510 µg/L, respectively, which were used for risk assessment in two port scenarios. Although the risks vary with the scale of the hull cleaning and the ports, in-water cleaning poses clear risks to marine environments, unless the effluents are recovered or treated before being released.

Repeated intratracheal instillation of zinc oxide nanoparticles induced pulmonary damage and a systemic inflammatory response in cynomolgus monkeys.

Recently, some researchers have demonstrated that inhaled zinc oxide nanoparticles (ZnONPs) induce an acute systemic inflammatory response in workers. Considering nonhuman primates are preferably considered an animal model for translational research due to their proven similarity with humans in terms of genetics and physiology, we intratracheally instilled ZnONPs to cynomolgus monkey for 14 days and identified the toxic mechanism and bioaccumulation. ZnONPs were rapidly ionized or aggregated in a simulated pulmonary fluid, and they attracted neutrophils to the lungs and increased the pulmonary level of inflammatory mediators. Additionally, thickened alveolar walls, fibrin clots, and hemorrhages were observed in the lungs of the monkeys instilled with the higher dose accompanied by cell debris in the alveolar ducts and alveoli. Dark-field microscopy images revealed translocation of ZnONPs into other tissues accompanied by an increase in the relative weight of livers to body weight. In addition, when instilled at the higher dose, the albumin/globulin ratio notably decreased compared to the control, whereas the C-reactive protein (CRP) level was significantly elevated. ZnONPs also clearly induced apoptotic cell death in a 24 h exposure to alveolar macrophages. Taken together, part of inhaled ZnONPs may be ionized in the lung, resulting in acute toxic effects, including cell death and tissue damage, and the rest may move to other tissues in the form of particles, causing a systemic inflammatory response. Based on the proven evidence among workers, we also suggest that the CRP level can be recommended as a biomarker for ZnONPs-induced adverse health effects.

Arsenic exposure combined with nano- or microplastic induces different effects in the marine rotifer Brachionus plicatilis.

Besides the adverse biological effects induced by microplastics (MPs), the effects associated with sorption of ambient pollutants on MPs are considered as an emerging environmental problem as MPs act as a mediator of pollutants. The present study examines the combined effects of nano(micro)plastics (NMPs) and arsenic (As) by exposing the marine rotifer Brachionus plicatilis to MP particles at the micro-scale (6 µm) and nano-scale (nanoplastics, NPs) (50 nm) along with As. In vivo toxicity, bioaccumulation, and biochemical reactions were used to examine the effects of combined exposure. The results of in vivo experiments showed that As toxicity increased with NP exposure, whereas toxicity was alleviated by MPs, indicating a different mode of action between NPs and MPs in combination with As. The highest level of As bioaccumulation was detected in NP + As groups, and followed by MP + As and As-only exposure groups, whereas no significant difference between groups was shown for As metabolites. In addition, the activity of several ATP-binding cassette proteins that confer multixenobiotic resistance, which is responsible for efflux of As, was activated by As but significantly inhibited by NP exposure, supporting the findings of in vivo experiments. Our results show that the effects of combining exposure to As with NP and MPs differ depending on particle size and provide an in-depth understanding of both environmental pollutants.

Drug resistance-free cytotoxic nanodrugs in composites for cancer therapy.

Drug resistance is a major cause of treatment failure for small-molecule cancer chemotherapies, despite the advances in combination therapies, drug delivery systems, epigenetic drugs, and proteolysis-targeting chimeras. Herein, we report the use of a drug resistance-free cytotoxic nanodrug as an alternative to small-molecule drugs. The present nanodrugs comprise 2 nm core gold nanoparticles (AuNPs) covered completely with multivalent hydrocarbon chains to a final diameter of ∼10 nm as single drug molecules. This hydrophobic drug-platform was delivered in composite form (∼35 nm) with block-copolymer like other small-molecular drugs. Upon uptake by cells, the nanodrugs enhanced the intracellular levels of reactive oxygen species and induced apoptosis, presumably reflecting multivalent interactions between aliphatic chains and intracellular biomolecules. No resistance to our novel nanodrug was observed following multiple treatment passages and the potential for use in cancer therapy was verified in a breast cancer patient-derived xenograft mouse model. These findings provide insight into the use of nano-scaled compounds as agents that evade drug resistance to cancer therapy.

Toxicity of orally administered food-grade titanium dioxide nanoparticles.

This year, France banned the application of titanium dioxide nanoparticles as a food additive (hereafter, E171) based on the insufficient oral toxicity data. Here, we investigated the subchronic toxic responses of E171 (0, 10, 100, and 1,000 mg/kg) and tried to elucidate the possible toxic mechanism using AGS cells, a human stomach epithelial cell line. There were no dose-related changes in the Organisation for Economic Cooperation and Development test guideline-related endpoints. Meanwhile, E171 deeply penetrated cells lining the stomach tissues of rats, and the IgM and granulocyte-macrophage colony-stimulating factor levels were significantly lower in the blood from rats exposed to E171 compared with the control. The colonic antioxidant protein level decreased with increasing Ti accumulation. Additionally, after 24-h exposure, E171 located in the perinuclear region of AGS cells and affected expression of endoplasmic reticulum stress-related proteins. However, cell death was not observed up to the used maximum concentration. A gene profile analysis also showed that immune response-related microRNAs were most strongly affected by E171 exposure. Collectively, we concluded that the NOAEL of E171 for 90 days repeated oral administration is between 100 and 1,000 mg/kg for both male and female rats. Additionally, further study is needed to clarify the possible carcinogenesis following the chronic accumulation in the colon.

Characterization of hazards and environmental risks of wastewater effluents from ship hull cleaning by hydroblasting.

Hydroblasting is used to remove biofouling and exhausted antifouling paints from ship hulls. Effluents generated from this process contain paint particles, metals, and booster biocides that may have toxic effects on organisms. To understand the potential risks of effluent discharge on marine environments, we analyzed the concentrations of metals in effluents collected during the dry-dock cleaning of ship hulls by hydroblasting. Copper and zinc were the principal metals, with concentrations ranging from 1440 to 9110 µg/L and 1800 to 22,600 µg/L, respectively. These concentrations are sufficiently high to cause harmful effects to most marine organisms. Model predictions suggested that the effluent discharge from hydroblasting posed risks to the wider marine environment of a hull-cleaning site, depending on the scale of the hull-cleaning operations and the size of the receiving environment, as well as various hydrodynamic factors. These effluents are inevitably hazardous, and their environmental release should be managed and regulated on the basis of site-specific risk assessments.

Effect of PM10 on pulmonary immune response and fetus development.

Despite numerous reports that ambient particulate matter is a key determinant for human health, toxicity data produced based on physicochemical properties of particulate matters is very lack, suggesting lack of scientific evidence for regulation. In this study, we sampled inhalable particulate matters (PM10) in northern Seoul, Korea. PM10 showed atypical- and fiber-type particles with the average size and the surface charge of 1,598.1 ± 128.7 nm and -27.5 ± 2.8, respectively, and various toxic elements were detected in the water extract. On day 90 after the first pulmonary exposure, total cell number dose-dependently increased in the lungs of both sexes of mice. PM10 induced Th1-dominant immune response with pathological changes in both sexes of mice. Meanwhile, composition of total cells and expression of proteins which functions in cell-to-cell communication showed different trends between sexes. Following, male and female mice were mated to identify effects of PM10 to the next generation. PM10 remained in the lung of dams until day 21 after birth, and the levels of IgA and IgE increased in the blood of dams exposed to the maximum dose compared to control. In addition, the interval between births of fetuses, the number of offspring, the neonatal survival rate (day 4 after birth) and the sex ratio seemed to be affected at the maximum dose, and particularly, all offspring from one dam were stillborn. In addition, expression of HIF-1α protein increased in the lung tissue of dams exposed to PM10, and level of hypoxia-related proteins was notably enhanced in PM10-exposed bronchial epithelial cells compared to control. Taken together, we suggest that inhaled PM10 may induce Th1-shifting immune response in the lung, and that it may affect reproduction (fetus development) by causing lung hypoxia. Additionally, we propose that further study is needed to identify particle-size-dependent effects on development of the next generation.

Inhaled underground subway dusts may stimulate multiple pathways of cell death signals and disrupt immune balance.

In this study, we aimed to identify a toxic mechanism and the potential health effects of ambient dusts in an underground subway station. At 24 h exposure to human bronchial epithelial (BEAS-2B) cells (0, 2.5, 10, and 40 µg/mL), dusts located within autophagosome-like vacuoles, whereas a series of autophagic processes appeared to be blocked. The volume, potential and activity of mitochondria decreased in consistent with a condensed configuration, and the percentage of late apoptotic cells increased accompanying S phase arrest. While production of reactive oxygen species, expression of ferritin (heavy chain) protein, secretion of IL-6, IL-8 and matrix metalloproteinases, and the released LDH level notably increased in dust-treated cells (40 µg/mL), intracellular calcium level decreased. At day 14 after a single instillation to mice (0, 12.5, 50, and 200 µg/head), the total number of cells increased in the lungs of dust-treated mice with no significant change in cell composition. The pulmonary levels of TGF-ß, GM-CSF, IL-12 and IL-13 clearly increased following exposure to dusts, whereas that of CXCL-1 was dose-dependently inhibited. Additionally, the population of cytotoxic T cells in T lymphocytes in the spleen increased relative to that of helper T cells, and the levels of IgA and IgM in the bloodstream were significantly reduced in the dust-treated mice. Subsequently, to improve the possibility of extrapolating our findings to humans, we repeatedly instilled dusts (1 time/week, 4 weeks, 0.25 and 1.0 mg/head) to monkeys. The total number of cells, the relative portion of neutrophils, the level of TNF-α significantly increased in the lungs of dust-treated monkeys, and the expression of cytochrome C was enhanced in the lung tissues. Meanwhile, the pulmonary level of MIP-α was clearly reduced, and the expression of caveolin-1 was inhibited in the lung tissues. More importantly, inflammatory lesions, such as granuloma, were seen in both mice and monkeys instilled with dusts. Taken together, we conclude that dusts may impair the host's immune function against foreign bodies by inhibiting the capacity for production of antibodies. In addition, iron metabolism may be closely associated with dust-induced cell death and inflammatory response.

Interspecific biotransformation and detoxification of arsenic compounds in marine rotifer and copepod.

The toxicity of arsenic (As) has been reported to be different depending on their chemical forms. However, its toxicity mechanisms largely remain unknown. In this study, to investigate toxicity mechanism of As in marine zooplanktons, namely, the rotifer Brachionus plicatilis and the copepod Paracyclopina nana, metabolites of As were analyzed by using a high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry with in vivo toxicity and antioxidant responses in response to inorganic As, including arsenate (AsV) and arsenite (AsIII). While AsIII was more toxic than AsV in both organisms, the rotifer B. plicatilis exhibited stronger tolerance, compared to the copepod P. nana. The As speciation analysis revealed differences in biotransformation processes in two species with B. plicatilis having a more simplified process than P. nana, contributing to a better tolerance against As in the rotifer B. plicatilis compared to P. nana. Moreover, the levels of GSH content and the regulation of omega class glutathione S-transferases were different in response to oxidative stress between B. plicatilis and P. nana. These results suggest that the rotifer B. plicatilis has a unique survival strategy with more efficient biotransformation and antioxidant responses, compared to P. nana, conferring higher tolerance to As.

Impacts of typhoon-induced heavy rainfalls and resultant freshwater runoff on the partitioning of organic carbon oxidation and nutrient dynamics in the intertidal sediments of the Han River estuary, Yellow Sea.

Occurrence of typhoons accompanied by heavy precipitation has increased for the past 40 years in northeast Asia. To elucidate the impact of three consecutive typhoon-induced heavy rainfall events and resultant freshwater runoff on the partitioning of organic carbon (Corg) oxidation and nutrient dynamics, we investigated the geochemical constituents, the rate of anaerobic Corg oxidation, sulfate reduction (SR), iron reduction (FeR) and P speciation in the intertidal mud flat of the Han River estuary, Yellow Sea. Corg oxidation by SR and FeR and their metabolic products (∑CO2, NH4+, H2S, Fe2+) decreased significantly (P < 0.05) during and immediately after the heavy rainfall. Additional mesocosm experiments demonstrated that potential N2 production rates increased up to 2.4 times with increased nitrate concentrations during freshwater runoff. The results suggest that denitrification becomes a significant Corg oxidation pathway substituting for SR during high-nitrate freshwater runoff, which may remove substantial portion of the N introduced into the estuary. P speciation analysis further revealed that the concentrations of iron bound P decreased by 2.2 fold during the heavy rainfall compared to that measured before the rainfall. The results suggest that an excess supply of riverine Si keeps P from binding to Fe, thereby stimulating P release. Taking projections of enhanced rainfall events in the future into account, our results suggest that the intensified storm events and resultant riverine runoff induces a shift of Corg oxidation pathways in the sediments, which ultimately alters C-N-P-S-Fe dynamics and may deepen N-limiting conditions in coastal ecosystems of the Yellow Sea.

Cigarette smoke extract may induce lysosomal storage disease-like adverse health effects.

Cigarette smoke is known to be associated with the incidence of a variety of pulmonary diseases, and alveolar macrophages are a key player in the defense mechanism against inhalable toxicants. Herein, we have found that a hydrophilic fraction in smoke extracts from 3R4F reference cigarettes (CSE) contains high concentrations of volatile substances compared to cigarette smoke condensate (amphoteric fraction). We also identified the toxic mechanism of CSE using MH-S, a mouse alveolar macrophage cell line. CSE decreased cell viability accompanying increased lactate dehydrogenase release. Additionally, mitochondrial volume and the potential increased along with enhanced expression of mitochondrial fusion proteins and decreased adenosine triphosphate production. Similarly, CSE clearly induced increase of catalase activity and intracellular calcium concentration and decrease of endoplasmic reticulum and lysosome volume at the highest dose. More interestingly, damaged organelles accumulated in the cytosol, and CSE-containing particles specifically penetrated to mitochondria. Meanwhile, any significant change in autophagy related protein expression was not found in CSE-treated cells. Subsequently, we evaluated the effects of CSE on secretion of inflammatory related cytokines and chemokines, considering the relationship between organelle damage and the disturbed immune response. Very importantly, we found that expression of innate and adaptive immunity related mediators is disrupted following CSE exposure. Taken together, we suggest that CSE may cause the accumulation of damaged organelles in the cytoplasm by impairing selective autophagic function. In addition, this accumulation is responsible for the inadequate ability of immune cells to repair the damage of lung tissue following exposure to CSE.

Whole cigarette smoke condensates induce ferroptosis in human bronchial epithelial cells.

Cigarette smoke is responsible for many fatal pulmonary diseases, however, the toxic mechanism is still unclear. In this study, we first confirmed that whole cigarette smoke condensates (WCSC) contain hydrophilic elements, lipophilic and gaseous components. Then, we treated BEAS-2B cells, a normal human bronchial epithelial cell line, at dosages of 0.25, 0.5, and 1% for 24 h and explored the toxic mechanism. Cell viability decreased in a dose-dependent manner, and fission and fusion of mitochondria, damage of endoplasmic reticulume (ER) structures, and formation of autophagosome-like vacuoles were found in cells treated with 1% WCSC. Mitochondrial and ER volumes, lysosomal fluorescence intensity, LDH release, and intracellular ROS levels notably decreased at the highest doses compared with the control, whereas intracellular calcium ion and NO levels were significantly elevated accompanying G2/M phase arrest. Expression of an iron-binding nuclear protein-related gene (pirin) was the most up-regulated in the WCSC-treated cells with enhanced expression of antioxidant-related genes, whereas expression of carbonic anhydrase IX gene, a marker of tumor hypoxia, was the most down-regulated. Additionally, levels of apoptosis (BAX, Apaf-1, and cleavage of caspase-3 and PARP), autophagy (p62 and LC3B-II), ER stress (PERK, IRE-1a, Bip, and CHOP), antioxidant (SOD-1 and SOD-2), and MAPkinase activation (p-ERK, p-p38, and p-JNK)-related proteins were clearly enhanced following exposure to WCSC, whereas expression of several mitochondrial dynamics-related proteins was reduced with dose. Interestingly, expression of ferritin protein (light chain) was dramatically enhanced near the ER along with that of p62 protein. More importantly, the hypoxia inducible factor-1 pathway and ferroptosis were proposed among the 20 terms in KEGG pathway analysis, and secretion of IL-6 and IL-8, which are involved in hypoxia-induced inflammation, were clearly elevated with dose. Taken together, we suggest that WCSC may induce ferroptosis in bronchial epithelial cells via ER stress and disturbed homeostasis in mitochondrial dynamics caused by induction of hypoxia conditions.

Production of Selenomethionine-Enriched Bifidobacterium bifidum BGN4 via Sodium Selenite Biocatalysis.

Selenium is a trace element essential for human health that has received considerable attention due to its nutritional value. Selenium's bioactivity and toxicity are closely related to its chemical form, and several studies have suggested that the organic form of selenium (i.e., selenomethionine) is more bioavailable and less toxic than its inorganic form (i.e., sodium selenite). Probiotics, especially Bifidobacteriium and Lactobacillus spp., have received increasing attention in recent years, due to their intestinal microbial balancing effects and nutraceutical benefits. Recently, the bioconversion (a.k.a biotransformation) of various bioactive molecules (e.g., minerals, primary and secondary metabolites) using probiotics has been investigated to improve substrate biofunctional properties. However, there have been few reports of inorganic selenium conversion into its organic form using Bifidobacterium and Lactobacillus spp. Here we report that the biosynthesis of organic selenium was accomplished using the whole cell bioconversion of sodium selenite under controlled Bifidobacterium bifidum BGN4 culture conditions. The total amount of organic and inorganic selenium was quantified using an inductively coupled plasma-atomic emission spectrometer (ICP-AES). The selenium species were separated via anion-exchange chromatography and analyzed with inductively coupled plasma-mass spectrometry (ICP-MS). Our findings indicated that the maximum level of organic selenium was 207.5 µg/g in selenium-enriched B. bifidum BGN4. Selenomethionine was the main organic selenium in selenium-enriched B. bifidum BGN4 (169.6 µg/g). Considering that B. bifidum BGN4 is a commercial probiotic strain used in the functional food industry with clinically proven beneficial effects, selenium-enriched B. bifidum BGN4 has the potential to provide dual healthy functions as a daily supplement of selenium and regulator of intestinal bacteria. This is the first report on the production of organic selenium using B. bifidum spp.

One-pot synthesis of layered double hydroxide hollow nanospheres with ultrafast removal efficiency for heavy metal ions and organic contaminants.

Herein, Mg/Fe layered double hydroxide (MF-LDH) hollow nanospheres were successfully prepared by a one-step thermal method. After the thermal treatment of MF-LDH nanospheres at 400 °C, the MF-LDH was converted into the corresponding oxide, Mg/Fe layered double oxide (MF-LDO), which maintained the hollow nanosphere structure. The MF-LDO hollow nanospheres exhibited excellent adsorption efficiency for both As(V) and Cr(VI), showing 99% removal within 5 min and providing maximum removal capacities of 178.6 mg g-1 [As(VI)] and 148.7 mg g-1 [Cr(VI)]. Moreover, it met the maximum contaminant level requirements recommended by World Health Organization (WHO); 10 ppm for As(V) and 50 ppm for Cr(VI) in 10 and 20 min, respectively. Furthermore, Au nanoparticles were successfully introduced in the MF-LDO hollow nanospheres, and the products showed a conversion rate of 100% for the reduction of 4-nitrophenol into 4-aminophenol within 5 min. It is believed that these excellent and versatile abilities integrated with a facile synthetic strategy will facilitate the practical application of this material in cost-effective wastewater purification.