-
Life Sciences Sep 2023The prevalence of metabolic syndrome (MetS), a cluster of serious medical conditions that raise the risk of lung cancer, has increased worldwide. Tobacco smoking (TS)...
AIM
The prevalence of metabolic syndrome (MetS), a cluster of serious medical conditions that raise the risk of lung cancer, has increased worldwide. Tobacco smoking (TS) potentially increases the risk of developing MetS. Despite the potential association of MetS with lung cancer, preclinical models that mimic human diseases, including TS-induced MetS, are limited. Here we evaluated the impact of exposure to tobacco smoke condensate (TSC) and two representative tobacco carcinogens, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNK) and benzo[a]pyrene (BaP), on MetS development in mice.
MATERIALS AND METHODS
FVB/N or C57BL/6 mice were exposed to vehicle, TSC, or NNK and BaP (NB) twice weekly for 5 months. The serum levels of total cholesterol (TCHO), triglycerides, high-density lipoprotein (HDL), blood glucose, and metabolites, along with glucose tolerance and body weight, were measured.
KEY FINDINGS
Compared with those of vehicle-treated mice, mice with TSC or NB exposure displayed major phenotypes associated with MetS, including increased serum levels of TCHO, triglycerides, and fasting and basal blood glucose and decreased glucose tolerance, and serum levels of HDL. These MetS-associated changes were found in both FVB/N and C57BL/6 mice that were susceptible or resistant to carcinogen-induced tumorigenesis, respectively, indicating that tumor formation is not involved in the TSC- or NB-mediated MetS. Moreover, oleic acid and palmitoleic acid, which are known to be associated with MetS, were significantly upregulated in the serum of TSC- or NB-treated mice compared with those in vehicle-treated mice.
SIGNIFICANCE
Both TSC and NB caused detrimental health problems, leading to the development of MetS in experimental mice.
Topics: Mice; Animals; Humans; Benzo(a)pyrene; 1-Butanol; Blood Glucose; Metabolic Syndrome; Mice, Inbred C57BL; Nitrosamines; Carcinogens; Lung Neoplasms
PubMed: 37423377
DOI: 10.1016/j.lfs.2023.121925 -
Molecules (Basel, Switzerland) Jul 2023Benzo[a]pyrene is a widespread environmental pollutant and a strong carcinogen. It is important to understand its bio-toxicity and degradation mechanism. Herein, we...
Benzo[a]pyrene is a widespread environmental pollutant and a strong carcinogen. It is important to understand its bio-toxicity and degradation mechanism. Herein, we studied the excited state dynamics of benzo[a]pyrene by using time-resolved fluorescence and transient absorption spectroscopic techniques. For the first time, it is identified that benzo[a]pyrene in its singlet excited state could react with oxygen, resulting in fluorescence quenching. Additionally, effective intersystem crossing can occur from its singlet state to the triplet state. Furthermore, the interaction between the excited benzo[a]pyrene and ct-DNA can be observed directly and charge transfer between benzo[a]pyrene and ct-DNA may be the reason. These results lay a foundation for further understanding of the carcinogenic mechanism of benzo[a]pyrene and provide insight into the photo-degradation mechanism of this molecule.
Topics: Benzo(a)pyrene; Oxygen; Kinetics; Chemical Phenomena; DNA
PubMed: 37446927
DOI: 10.3390/molecules28135269 -
Tobacco Induced Diseases 2024The essence of ferroptosis is the accumulation of membrane lipid peroxides caused by increased iron, which disrupts the redox balance within cells and triggers cell...
INTRODUCTION
The essence of ferroptosis is the accumulation of membrane lipid peroxides caused by increased iron, which disrupts the redox balance within cells and triggers cell death. Abnormal metabolism of iron significantly increases the risk of lung cancer and induces treatment resistance. However, the roles and mechanisms of smocking in ferroptosis in patients with lung cancer are still unclear.
METHODS
Our study was a secondary bioinformatics analysis followed by an experimental cell culture analysis. In this study, we identified the different ferroptosis-related genes and established the signature in lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) patients with different smocking status, based on The Cancer Genome Atlas (TCGA) database. Fanyl diphosphate fanyl transferase 1 (FDFT1) in LUSC patients and solute carrier one family member 5 (SLC1A5) in LUAD patients were confirmed to be related to ferroptosis. Next, we checked the roles of two main components of smoke, nicotine, and benzo(a)pyrene (BaP), in ferroptosis of non-small-cell lung cancer (NSCLC) cells.
RESULTS
We confirmed that nicotine inhibited reactive oxygen species (ROS) levels and induced glutathione peroxidase (GPX4) expression, while the opposite roles of BaP were observed in NSCLC cells. Mechanically, nicotine protected NSCLC cells from ferroptosis through upregulation of epidermal growth factor receptor (EGFR) and SLC1A5 expression. BaP-induced ferroptosis in NSCLC cells depends on FDFT1 expression.
CONCLUSIONS
In this study, the ferroptosis-associated gene signature was identified in LUAD and LUSC patients with different smoking status. We confirmed nicotine-protected LUAD and LUSC cells from ferroptosis by upregulating EGFR and SLC1A5 expression. BaP-induced ferroptosis in these cells depends on FDFT1 expression.
PubMed: 38947555
DOI: 10.18332/tid/189490 -
Inorganic Chemistry Jun 2024Three novel bismuth-organic compounds, with the general formula [Bi(HPDC)(PDC)]·(arene)·2HO (HPDC = 2,6-pyridinedicarboxylic acid; arene = pyrene, naphthalene, and...
Three novel bismuth-organic compounds, with the general formula [Bi(HPDC)(PDC)]·(arene)·2HO (HPDC = 2,6-pyridinedicarboxylic acid; arene = pyrene, naphthalene, and azulene), that consist of neutral dinuclear Bi-pyridinedicarboxylate complexes and outer coordination sphere arene molecules were synthesized and structurally characterized. The structures of all three phases exhibit strong π-π stacking interactions between the Bi-bound PDC/HPDC and outer sphere organic molecules; these interactions effectively sandwich the arene molecules between bismuth complexes and thereby prevent molecular vibrations. Upon UV irradiation, the compounds containing pyrene and naphthalene displayed red and green emission, respectively, with quantum yields of 1.3(2) and 30.8(4)%. The emission was found to originate from the T → S transition of the corresponding arene and result in phosphorescence characteristic of the arene employed. By comparison, the azulene-containing compound displayed very weak blue-purple phosphorescence of unknown origin and is a rare example of T → S emission from azulene. The pyrene- and naphthalene-containing compounds both display radioluminescence, with intensities of 11 and 38% relative to bismuth germanate, respectively. Collectively, these results provide further insights into the structure-property relationships that underpin luminescence from Bi-based materials and highlight the utility of Bi-organic molecules in the realization of organic emission.
PubMed: 38823026
DOI: 10.1021/acs.inorgchem.4c00606 -
Organic & Biomolecular Chemistry Dec 2023The considerable need for novel polyaromatic hydrocarbons (PAHs) for applications in the area of organic electronics remains unchanged. Diacenaphthopyrene represents a...
The considerable need for novel polyaromatic hydrocarbons (PAHs) for applications in the area of organic electronics remains unchanged. Diacenaphthopyrene represents a new PAH consisting of two acenaphthylene units connected by a pyrene bridge. The system is built up by Pd-catalyzed cross-coupling, followed by acid catalyzed cyclosiomerization to generate the pyrene moiety. The new fused scaffold is formed in the last step in convincing yields by means of CH-activation. We additionally synthesized one aza-pyrene based analogue. The two hitherto unknown PAHs were investigated in detail by UV-Vis and PL spectroscopy, CV measurements and DFT calculations. Based on these results, the abilities of the novel structure as well as the effect of incorporation of nitrogen were evaluated.
PubMed: 38044660
DOI: 10.1039/d3ob01744c -
Analytical Sciences : the International... Sep 2023The sensitive, non-destructive constant wavelength (CW) and constant energy (CE) SFS techniques have been used for the simultaneous determination of 1-amino pyrene (AP)...
The sensitive, non-destructive constant wavelength (CW) and constant energy (CE) SFS techniques have been used for the simultaneous determination of 1-amino pyrene (AP) and 1-napthyl amine (NA) in their mixtures without prior separation via optimization of different experimental conditions (Δλ 70.0 nm, Δν 4000.0 cm, scan rate 240.0 nm/min, 25.0 °C, methanol). Amplitude-concentration plots have been linear for 1-amino pyrene, AP (0.01-0.1 mg/L) and 1-napthyl amine, NA (0.1-1.0 mg/L). In aqueous methanolic binary mixtures, the mean recoveries (RSD, LOD and LOQ) of AP were found to be 100.09% (0.053, 0.008 mg/L and 0.034 mg/L) for emission, 100.11% (0.141, 0.008 mg/L, 0.034 mg/L) for CWSFS, 100.05% (0.109, 0.007 mg/L and 0.032 mg/L) for first derivative CWSFS, 100.00% (0.148, 0.007 mg/L and 0.031 mg/L) for CESFS, 99.99% (0.109, 0.008 mg/L and 0.035 mg/L) for first derivative CESFS modes respectively. Additionally, for NA the mean recoveries (RSD, LOD and LOQ) were 100.29% (0.360, 0.046 mg/L and 0.204 mg/L) for emission, 100.06% (0.089, 0.098 mg/L, 0.436 mg/L) for CWSFS, 100.09% (0.144, 0.065 mg/L and 0.288 mg/L) for first derivative CWSFS, 100.05% (0.178, 0.077 mg/L and 0.339 mg/L) for CESFS, 100.03% (0.181, 0.082 mg/L and 0.364 mg/L) for first derivative CESFS modes respectively. Considering their safety and greenness, these methods might be considered as green tools using analytical eco-scale approaches (eco-scale score 88.0).
PubMed: 37244980
DOI: 10.1007/s44211-023-00368-8 -
Biomacromolecules Sep 2023A chitosan derivative (Pyr-CS-HTAP) having pyrene (Pyr) and -[(2-hydroxyl-3-trimethylammonium)] propyl (HTAP) units conjugated at C6 and C2 positions, respectively, was...
A chitosan derivative (Pyr-CS-HTAP) having pyrene (Pyr) and -[(2-hydroxyl-3-trimethylammonium)] propyl (HTAP) units conjugated at C6 and C2 positions, respectively, was synthesized and characterized. Dynamic light scattering and scanning electron microscopy revealed that Pyr-CS-HTAP self-assembled into spherical nanoparticles with a hydrodynamic diameter of 211 ± 5 nm and a ζ-potential of +49 mV. The successful binding of Pyr-CS-HTAP with nucleic acid was ascertained by fluorescence resonance energy-transfer analysis and gel electrophoresis. Pyr-CS-HTAP facilitated the cellular uptake of nucleic acid up to 99%. Co-localization analysis using fluorescence microscopy revealed the endosomal escape of the Pyr-CS-HTAP/nucleic acid complexes and the successful release of the nucleic acid cargoes from the polyplexes into the nucleus. It is strongly believed that Pyr-CS-HTAP can potentially be developed into a fluorescently trackable gene delivery system in the future.
Topics: Chitosan; Nucleic Acids; Nanoparticles; Cell Line, Tumor; Pyrenes
PubMed: 37549394
DOI: 10.1021/acs.biomac.3c00301 -
Beilstein Journal of Organic Chemistry 2023Electron and hole transport characteristics were evaluated for perylene-based and pyrene-based compounds using electron-only and hole-only devices. The perylene...
Electron and hole transport characteristics were evaluated for perylene-based and pyrene-based compounds using electron-only and hole-only devices. The perylene presented a columnar hexagonal liquid crystal phase at room temperature with strong molecular π-stacking inside the columns. The pyrene crystallizes bellow 166 °C, preserving the close-packed columnar rectangular structure of the mesophase. Photophysical analysis and numerical calculations assisted the interpretation of positive and negative charge carrier mobilities obtained from fitting the space charge limited regime of current vs voltage curves. The pyrene-based material demonstrated an electron mobility two orders of magnitude higher than the perylene one, indicating the potential of this class of materials as electron transporting layer.
PubMed: 38025088
DOI: 10.3762/bjoc.19.128 -
Pharmaceutics Sep 2023Research on platinum-based anticancer drugs continuously strives to develop new non-classical platinum complexes. Pt(IV) prodrugs are the most promising, and their...
Research on platinum-based anticancer drugs continuously strives to develop new non-classical platinum complexes. Pt(IV) prodrugs are the most promising, and their activation-by-reduction mechanism of action is being explored as a prospect for higher selectivity and efficiency. Herein, we present the anticancer potency and chemical reactivity of Pt(IV) complexes formed by linking pyrene butyric acid with cisplatin. The results from cytotoxicity screening on 10 types of cancer cell lines and non-malignant cells (HEK-293) indicated IC values as low as 50-70 nM for the monosubstituted Pt(IV) complex against leukemia cell lines (HL-60 and SKW3) and a cisplatin-resistant derivative (HL-60/CDDP). Interestingly, the bis-substituted complex is virtually non-toxic to both healthy and cancerous cells of adherent types. Nevertheless, it shows high cytotoxicity against multidrug-resistant derivatives HL-60/CDDP and HL-60/Dox. The reactivity of the complexes with biological reductants was monitored by the NMR method. Furthermore, the platinum uptake by the treated cells was examined on two types of cellular cultures: adherent and suspension growing, and proteome profiling was conducted to track expression changes of key apoptosis-related proteins in HL-60 cells. The general conclusion points to a possible cytoskeletal entrapment of the bulkier bis-pyrene complex that could be limiting its cytotoxicity to adherent cells, both cancerous and healthy ones.
PubMed: 37765279
DOI: 10.3390/pharmaceutics15092310 -
Microbiological Research Aug 2023Polycyclic aromatic hydrocarbons (PAHs) are diverse pollutants of significant environmental concerns, requiring effective biodegradation. This study used different...
Polycyclic aromatic hydrocarbons (PAHs) are diverse pollutants of significant environmental concerns, requiring effective biodegradation. This study used different bioinformatics tools to conduct whole-genome sequencing of two novel bacterial strains, Klebsiella michiganensis EF4 and K. oxytoca ETN19, to improve our understanding of their many genomic functions and degradation pathways of phenanthrene and pyrene. After 28 days of cultivation, strain EF4 degraded approximately 80% and 60% of phenanthrene and pyrene, respectively. However, their combinations (EF4 +ETN19) showed tremendous phenanthrene degradation efficiency, supposed to be at the first-level kinetic model with a t value of approximately 6 days. In addition, the two bacterial genomes contained carbohydrate-active enzymes and secondary metabolites biosynthetic gene clusters associated with PAHs degradation. The two genomes contained the bZIP superfamily of transcription factors, primarily the cAMP-response element-binding protein (CREB), which could regulate the expression of several PAHs degradation genes and enzymes. Interestingly, the two genomes were found to uniquely degrade phenanthrene through a putative pathway that catabolizes 2-carboxybenzalpyruvate into the TCA cycle. An operon containing multicomponent proteins, including a novel gene (JYK05_14550) that could initiate the beginning step of phenanthrene and pyrene degradation, was found in the EF4 genome. However, the degradation pathway of ETN19 showed that the yhfP gene encoding putative quinone oxidoreductase was associated with phenanthrene and pyrene catabolic processes. Furthermore, the significant expression of catechol 1,2-dioxygenase and quinone oxidoreductase genes in EF4 +ETN19 and ETN19 following the quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis confirmed the ability of the bacteria combination to degrade pyrene and phenanthrene effectively. These findings present new insight into the possible co-metabolism of the two bacterial species in the rapid biodegradation of phenanthrene and pyrene in soil environments.
Topics: Klebsiella oxytoca; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Pyrenes; Bacteria; Biodegradation, Environmental; Oxidoreductases; Sequence Analysis; Quinones
PubMed: 37178499
DOI: 10.1016/j.micres.2023.127410