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Ecotoxicology and Environmental Safety Jun 2024PIWI-interacting RNAs (piRNAs) is an emerging class of small non-coding RNAs that has been recently reported to have functions in infertility, tumorigenesis, and...
PIWI-interacting RNAs (piRNAs) is an emerging class of small non-coding RNAs that has been recently reported to have functions in infertility, tumorigenesis, and multiple diseases in humans. Previously, 5 toxicity pathways were proposed from hundreds of toxicological studies that underlie BaP-induced lung injuries, and a "Bottom-up" approach was established to identify small non-coding RNAs that drive BaP-induced pulmonary effects by investigating the activation of these pathways in vitro, and the expression of the candidate microRNAs were validated in tissues of patients with lung diseases from publications. Here in this study, we employed the "Bottom-up" approach to identifying the roles of piRNAs and further validated the mechanisms in vivo using mouse acute lung injury model. Specifically, by non-coding RNA profiling in in vitro BaP exposure, a total of 3 suppressed piRNAs that regulate 5 toxicity pathways were proposed, including piR-004153 targeting CYP1A1, FGFR1, ITGA5, IL6R, NGRF, and SDHA, piR-020326 targeting CDK6, and piR-020388 targeting RASD1. Animal experiments demonstrated that tail vein injection of respective formulated agomir-piRNAs prior to BaP exposure could all alleviate acute lung injury that was shown by histopathological and biochemical evidences. Immunohistochemical evaluation focusing on NF-kB and Bcl-2 levels showed that exogenous piRNAs protect against BaP-induced inflammation and apoptosis, which further support that the inhibition of the 3 piRNAs had an important impact on BaP-induced lung injuries. This mechanism-driven, endpoint-supported result once again confirmed the plausibility and efficiency of the approach integrating in silico, in vitro, and in vivo evidences for the purpose of identifying key molecules.
Topics: Animals; Mice; RNA, Small Interfering; Benzo(a)pyrene; Acute Lung Injury; Lung Injury; Male; Mice, Inbred C57BL; Humans; Piwi-Interacting RNA
PubMed: 38636406
DOI: 10.1016/j.ecoenv.2024.116330 -
RSC Advances Apr 2024There have been scarce reports about stereoscopic design of N-heteroacenes (NHAs), especially for the electron-deficient π-building blocks. Herein, we report the design...
There have been scarce reports about stereoscopic design of N-heteroacenes (NHAs), especially for the electron-deficient π-building blocks. Herein, we report the design and synthesis of a U-shaped bis(pyrene-quinoxaline) (BPQ). Single crystal X-ray diffraction reveals the herringbone stacking pattern and the presence of regular and incompletely closed pores.
PubMed: 38617572
DOI: 10.1039/d4ra00788c -
Current Research in Neurobiology 2024Alzheimer's disease (AD) is a neurodegenerative disease that affects the neurons in the hippocampus, resulting in cognitive and memory impairment. The most prominent...
Alzheimer's disease (AD) is a neurodegenerative disease that affects the neurons in the hippocampus, resulting in cognitive and memory impairment. The most prominent clinical characteristics of AD are the production of amyloid-beta (Aβ) plaques, neurofibrillary tangles, and neuroinflammation in neurons. It has been proven that embelin (Emb) possesses antioxidant, anti-inflammatory, and neuroprotective properties. Therefore, we assessed the therapeutic potential of Emb in Benzo [α]pyrene (BaP)-induced cognitive impairment in experimental mice. BaP (5 mg/kg, i. p) was given to mice daily for 28 days, and Emb (2.5, 5, and 10 mg/kg, i. p) was given from 14 to 28 days of a protocol. In addition, locomotor activity was evaluated using open-field and spatial working, and non-spatial memory was evaluated using novel object recognition tasks (NORT), Morris water maze (MWM), and Y- maze. At the end of the study, the animal tissue homogenate was used to check biochemicals, neuroinflammation, and neurotransmitter changes. BaP-treated mice showed a significant decline in locomotor activity, learning and memory deficits and augmented oxidative stress (lipid peroxidation, nitrite, and GSH). Further, BaP promoted the release of inflammatory tissue markers, decreased acetylcholine, dopamine, GABA, serotonin, and norepinephrine, and increased glutamate concentration. However, treatment with Emb at dose-dependently prevented biochemical changes, improved antioxidant levels, reduced neuroinflammation, restored neurotransmitter concentration, and inhibited the NF-κB pathway. The current study's finding suggested that Emb improved cognitive functions through antioxidant, anti-inflammatory, and neuroprotective mechanisms and inhibition of acetylcholinesterase (AChE) enzyme activities and Aβ-42 accumulation.
PubMed: 38616958
DOI: 10.1016/j.crneur.2023.100122 -
Environmental Pollution (Barking, Essex... Jun 2024Urbanization has numerous benefits to human society, but some aspects of urban environments, such as air pollution, can negatively affect human health. Two major air... (Meta-Analysis)
Meta-Analysis Review
Urbanization has numerous benefits to human society, but some aspects of urban environments, such as air pollution, can negatively affect human health. Two major air pollutants, particulate matter (PM) and polycyclic aromatic hydrocarbons (PAH), have been classified as carcinogens by the International Agency for Research on Cancer. Here, we answer two questions: (1) What are the carcinogenic effects of PM and PAH exposure? (2) How does carcinogenic risk vary across geographical regions? We performed a comprehensive literature search of peer-reviewed published studies examining the link between air pollution and human cancer rates. Focusing on studies published since 2014 when the last IARC monograph on air pollution was published, we converted the extracted data into relative risks and performed subgroup analyses. Exposure to PM (per 10 μg/m) resulted in an 8.5% increase in cancer incidence when all cancer types were combined, and risk for individual cancer types (i.e. lung cancer and adenocarcinoma) was also elevated. PM was also associated with 2.5% higher mortality due to cancer when all types of cancer were combined, and for individual cancer types (i.e., lung and breast cancer). Exposure to PM and PM posed the greatest risk to lung cancer incidence and mortality in Europe (PM RR 2.15; PM RR 1.26); the risk in Asia and the Americas was also elevated. Exposure to PAH and benzo[a]pyrene significantly increased the pooled risk of cancer incidence (10.8% and 8.0% respectively) at the highest percentile of exposure concentration. Our meta-analyses of studies over the past decade shows that urban air pollution in the form of PM, PM, and PAH all elevate the incidence and mortality of cancer. We discuss the possible mechanisms of carcinogenesis of PM and PAH. These results support World Health Organization's conclusion that air pollution poses among the greatest health risks to humans living in cities.
Topics: Particulate Matter; Polycyclic Aromatic Hydrocarbons; Humans; Air Pollutants; Neoplasms; Environmental Exposure; Air Pollution; Carcinogens
PubMed: 38614427
DOI: 10.1016/j.envpol.2024.123941 -
International Journal of Molecular... Mar 2024Lung cancer is the leading cause of cancer death worldwide. Polycyclic aromatic hydrocarbons (PAHs) are metabolized by the cytochrome P450 (CYP)1A and 1B1 to...
Lung cancer is the leading cause of cancer death worldwide. Polycyclic aromatic hydrocarbons (PAHs) are metabolized by the cytochrome P450 (CYP)1A and 1B1 to DNA-reactive metabolites, which could lead to mutations in critical genes, eventually resulting in cancer. Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial against cancers. In this investigation, we elucidated the mechanisms by which omega-3 fatty acids EPA and DHA will attenuate PAH-DNA adducts and lung carcinogenesis and tumorigenesis mediated by the PAHs BP and MC. Adult wild-type (WT) (A/J) mice, -null, -null, or -null mice were exposed to PAHs benzo[a]pyrene (BP) or 3-methylcholanthrene (MC), and the effects of omega-3 fatty acid on PAH-mediated lung carcinogenesis and tumorigenesis were studied. The major findings were as follows: (i) omega-3 fatty acids significantly decreased PAH-DNA adducts in the lungs of each of the genotypes studied; (ii) decreases in PAH-DNA adduct levels by EPA/DHA was in part due to inhibition of CYP1B1; (iii) inhibition of soluble epoxide hydrolase (sEH) enhanced the EPA/DHA-mediated prevention of pulmonary carcinogenesis; and (iv) EPA/DHA attenuated PAH-mediated carcinogenesis in part by epigenetic mechanisms. Taken together, our results suggest that omega-3 fatty acids have the potential to be developed as cancer chemo-preventive agents in people.
Topics: Humans; Adult; Mice; Animals; Fatty Acids, Omega-3; DNA Adducts; Carcinogenesis; Cell Transformation, Neoplastic; Docosahexaenoic Acids; Eicosapentaenoic Acid; Polycyclic Aromatic Hydrocarbons
PubMed: 38612589
DOI: 10.3390/ijms25073781 -
Molecules (Basel, Switzerland) Mar 2024Pyrene derivatives are regularly proposed for use in biochemistry as dyes due to their photochemical characteristics. Their antibacterial properties are, however, much...
Pyrene derivatives are regularly proposed for use in biochemistry as dyes due to their photochemical characteristics. Their antibacterial properties are, however, much less well understood. New complexes based on 4-[()-2-(1-pyrenyl)vinyl]pyridine (PyPe) have been synthesized with metal ions that are known to possess antimicrobial properties, such as zinc(II), cadmium(II), and mercury(II). The metal ion salts, free ligand, combinations thereof, and the coordination compounds themselves were tested for their antibacterial properties through microdilution assays. We found that the ligand is able to modulate the antibacterial properties of transition metal ions, depending on the complex stability, the distance between the ligand and the metal ions, and the metal ions themselves. The coordination by the ligand weakened the antibacterial properties of heavy metal ions (Cd(II), Hg(II), Bi(III)), allowing the bacteria to survive higher concentrations thereof. Mixing the ligand and the metal ion salts without forming the complex beforehand enhanced the antibacterial properties of the cations. Being non-cytotoxic itself, the ligand therefore balances the biological consequences of heavy metal ions between toxicity and therapeutic weapons, depending on its use as a coordinating ligand or simple adjuvant.
Topics: Ligands; Salts; Metals, Heavy; Mercury; Ions; Anti-Bacterial Agents; Alkenes; Polymers; Pyridines
PubMed: 38611844
DOI: 10.3390/molecules29071565 -
The Science of the Total Environment Jun 2024The presence of nanoplastics (NPs) and microplastics (MPs) in the environment is recognised as a global-scale problem. Due to their hydrophobic nature and large specific...
The presence of nanoplastics (NPs) and microplastics (MPs) in the environment is recognised as a global-scale problem. Due to their hydrophobic nature and large specific surface, NPs and MPs can adsorb other contaminants, as polycyclic aromatic hydrocarbons (PAHs), and modulate their bioavailability and hazard. Adult zebrafish were exposed for 3 and 21 days to: (1) 0.07 mg/L NPs (50 nm), (2) 0.05 mg/L MPs (4.5 μm), (3) MPs with sorbed oil compounds of the water accommodated fraction (WAF) of a naphthenic crude oil (MPs-WAF), (4) MPs with sorbed benzo(a)pyrene (MPs-B(a)P), (5) 5 % WAF and (6) 21 μg/L B(a)P. Electrodense particles resembling NPs were seen in the intestine lumen close to microvilli. MPs were abundantly found in the intestine lumen, but not internalised into the tissues. After 21 days, NPs caused a significant downregulation of cat, and upregulation of gpx1a and sod1, while MPs upregulated cyp1a and increased the prevalence of liver vacuolisation. No histopathological alteration was observed in gills. In this study, contaminated MPs did not increase PAH levels in zebrafish but results highlight the potential differential impact of plastic particles depending on their size, making it necessary to urgently address the ecotoxicological impact of real environmental NPs and MPs.
Topics: Animals; Zebrafish; Microplastics; Water Pollutants, Chemical; Polycyclic Aromatic Hydrocarbons; Polystyrenes; Nanoparticles
PubMed: 38604358
DOI: 10.1016/j.scitotenv.2024.172380 -
Analytical and Bioanalytical Chemistry Jun 2024While field ionization (FI) and field desorption (FD) are established soft vacuum ionization methods in mass spectrometry (MS), the technique of atmospheric pressure...
While field ionization (FI) and field desorption (FD) are established soft vacuum ionization methods in mass spectrometry (MS), the technique of atmospheric pressure field desorption (APFD) has only recently been added to the repertoire. Similar to FI and FD, APFD can yield both positive even-electron ions of highly polar or ionic compounds and positive molecular ions, M, e.g., of polycyclic aromatic compounds. Thus, a dedicated APFD source assembly has been constructed and demonstrated to allow for robust APFD operation. This device also enabled observation of the emitter during operation and allowed for resistive emitter heating, thereby speeding up the desorption of the analytes and expanding the range of analytes accessible to APFD. While initial work was done using a Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometer, the new APFD source offered the flexibility to also be used on a trapped ion mobility-quadrupole-time-of-flight (TIMS-Q-TOF) instrument, and thus, it would be possible to be mounted to any Bruker mass spectrometer featuring an atmospheric pressure (AP) interface. Operating an APFD source at a TIMS-Q-TOF instrument called for the exploration of the combined use of APFD and TIMS. Here, operation, basic properties, and capabilities of this new atmospheric pressure field desorption-trapped ion mobility-mass spectrometry (APFD-TIMS-MS) coupling are described. APFD-TIMS-MS is employed for the separation of individual components of oligomers and for the accurate determination of their collision cross section (CCS). This work describes the application of APFD-TIMS-MS on poly(ethylene glycol) forming [M + Na] ions by cationization and on an amine-terminated poly(propylene glycol) yielding [M + H] ions. Some compounds forming molecular ions, M, by field ionization such as [60]fullerene and a mixture of four polycyclic aromatic hydrocarbons (PAHs) are examined. In APFD-TIMS-MS, the limits of detection (LODs) of fluoranthene and benzo[a]pyrene M ions are determined as ≈100 pg and <1 pg, respectively. Finally, [60]fullerene is analyzed by negative-ion APFD-TIMS-MS where it yields a molecular anion, M.
PubMed: 38589615
DOI: 10.1007/s00216-024-05282-0 -
Advanced Science (Weinheim,... Jun 2024Rationally designed organic redox-active materials have attracted numerous interests due to their excellent electrochemical performance and reasonable sustainability....
Rationally designed organic redox-active materials have attracted numerous interests due to their excellent electrochemical performance and reasonable sustainability. However, they often suffer from poor cycling stability, intrinsic low operating potential, and poor rate performance. Herein, a novel Donor-Acceptor (D-A) bipolar polymer with n-type pyrene-4,5,9,10-tetraone unit storing Li cations and p-type carbazole unit which attracts anions and provides polymerization sites is employed as a cathode for lithium-ion batteries through in situ electropolymerization. The multiple redox reactions and boosted kinetics by the D-A structure lead to excellent electrochemical performance of a high discharge capacity of 202 mA h g at 200 mA g, impressive working potential (2.87 and 4.15 V), an outstanding rate capability of 119 mA h g at 10 A g and a noteworthy energy density up to 554 Wh kg. This strategy has significant implications for the molecule design of bipolar organic cathode for high cycling stability and high energy density.
PubMed: 38582519
DOI: 10.1002/advs.202310239 -
Ecotoxicology and Environmental Safety May 2024Benzo(a)pyrene (BaP) can be detected in the human placenta. However, little is known about the effects of BaP exposure on different placental cells under various...
Benzo(a)pyrene (BaP) can be detected in the human placenta. However, little is known about the effects of BaP exposure on different placental cells under various conditions. In this study, we aimed to investigate the effects of BaP on mitochondrial function, pyrin domain-containing protein 3 (NLRP3) inflammasome, and apoptosis in three human trophoblast cell lines under normoxia, hypoxia, and inflammatory conditions. JEG-3, BeWo, and HTR-8/SVneo cell lines were exposed to BaP under normoxia, hypoxia, or inflammatory conditions for 24 h. After treatment, we evaluated cell viability, apoptosis, aryl hydrocarbon receptor (AhR) protein and cytochrome P450 (CYP) gene expression, mitochondrial function, including mitochondrial DNA copy number (mtDNAcn), mitochondrial membrane potential (ΔΨm), intracellular adenosine triphosphate (iATP), and extracellular ATP (eATP), nitric oxide (NO), NLPR3 inflammasome proteins, and interleukin (IL)-1β. We found that BaP upregulated the expression of AhR or CYP genes to varying degrees in all three cell lines. Exposure to BaP alone increased ΔΨm in all cell lines but decreased NO in BeWo and HTR-8/SVneo, iATP in HTR-8/SVneo, and cell viability in JEG-3, without affecting apoptosis. Under hypoxic conditions, BaP did not increase the expression of AhR and CYP genes in JEG-3 cells but increased CYP gene expression in two others. Pro-inflammatory conditions did not affect the response of the 3 cell lines to BaP with respect to the expression of CYP genes and changes in the mitochondrial function and NLRP3 inflammasome proteins. In addition, in HTR-8/SVneo cells, BaP increased IL-1β secretion in the presence of hypoxia and poly(I:C). In conclusion, our results showed that BaP affected mitochondrial function in trophoblast cell lines by increasing ΔΨm. This increased ΔΨm may have rescued the trophoblast cells from activation of the NLRP3 inflammasome and apoptosis after BaP treatment. We also observed that different human trophoblast cell lines had cell type-dependent responses to BaP exposure under normoxia, hypoxia, or pro-inflammatory conditions.
Topics: Humans; Benzo(a)pyrene; Placenta; Cell Line; Female; Pregnancy; Apoptosis; Trophoblasts; Receptors, Aryl Hydrocarbon; Cell Survival; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammasomes; Mitochondria; Inflammation; Cell Hypoxia; Membrane Potential, Mitochondrial; Cytochrome P-450 Enzyme System; Basic Helix-Loop-Helix Transcription Factors
PubMed: 38579532
DOI: 10.1016/j.ecoenv.2024.116287