ABSTRACT
Organophosphorus flame retardants (PFRs) are a class of flame retardants and environmental pollutants with various biological effects. Recentstudies have evidenced activation of some PFRs by human CYP enzymes (including CYP2E1) for genotoxic effects. However, the activity of CYPs in fish species toward PFR metabolism remains unclear. This study was aimed on comparing the metabolism of triphenyl phosphate (TPHP) and 4-OH-TPHP in human, rat, and common carp, and the involvement of human CYP2E1 and its orthologs in the metabolism, by using fomepizole (4-MP, CYP2E1 inhibitor) as a modulator, in silico molecular docking and dynamics analyses. The rate of TPHP metabolism was apparently faster with human and rat, microsomes than with fish microsomes, the major metabolites were phosphodiester and hydroxylated phosphate, with 30-80â¯% of TPHP forming unidentified metabolites in the system of each species. 4-OH-TPHP was readily metabolized by both human and rat microsomes, whereas it was hardly metabolized in carp assays. Meanwhile, with 4-MP the transformation of TPHP to 4-OH-TPHP was enhanced in the human/rat systems while suppressed in the carp system. Moreover, the formation of unidentified metabolites in human and rat systems was mostly inhibited by 4-MP. Through molecular dynamics analysis TPHP and its primary metabolites showed high affinity for human and rat CYP2E1, as well as the carp ortholog (CYP2G1-like enzyme), however, the 4-OH-TPHP bond to the latter was too far from the heme to permit a biochemical reaction. This study suggests that the metabolism/activation of TPHP might be favored in mammals rather than carp, a fish species.
ABSTRACT
Persistent organic pollutants pose a great threat to amphibian populations, but information on the bioaccumulation of contaminants in amphibians remains scarce. To examine the tissue distribution and maternal transfer of organic halogenated pollutants (OHPs) in frogs, seven types of tissues from black-spotted frog (muscle, liver, kidney, stomach, intestine, heart, and egg) were collected from an e-waste-polluted area in South China. Among the seven frog tissues, median total OHP concentrations of 2.3 to 9.7 µg/g lipid weight were found (in 31 polychlorinated biphenyl [PCB] individuals and 15 polybrominated diphenyl ether [PBDE], dechlorane plus [syn-DP and anti-DP], bexabromobenzene [HBB], polybrominated biphenyl] PBB153 and -209], and decabromodiphenyl ethane [DBDPE] individuals). Sex-specific differences in contaminant concentration and compound compositions were observed among the frog tissues, and eggs had a significantly higher contaminant burden on the whole body of female frogs. In addition, a significant sex difference in the concentration ratios of other tissues to the liver was observed in most tissues except for muscle. These results suggest that egg production may involve the mobilization of other maternal tissues besides muscle, which resulted in the sex-specific distribution. Different parental tissues had similar maternal transfer mechanisms; factors other than lipophilicity (e.g., molecular size and proteinophilic characteristics) could influence the maternal transfer of OHPs in frogs. Environ Toxicol Chem 2024;43:1557-1568. © 2024 SETAC.
Subject(s)
Persistent Organic Pollutants , Animals , Female , Tissue Distribution , Male , Persistent Organic Pollutants/metabolism , Environmental Monitoring , Halogenated Diphenyl Ethers/metabolism , Anura/metabolism , China , Ranidae/metabolism , Water Pollutants, Chemical/metabolism , Water Pollutants, Chemical/analysisABSTRACT
Laying hens were exposed to feeds spiked with a series of perfluoroalkyl carboxylates (PFCAs) ranging from perfluorobutanoic acid (C4) to perfluorooctadecanoic acid (C18) to investigate their bioaccumulation, tissue distribution, and maternal transfer. We found that PFCAs with longer carbon chains (>8) were more efficiently absorbed in the gastrointestinal tract than those with shorter chains (≤8), and that the rate of depuration varied inversely with the carbon chain length in a U-shaped pattern. Moreover, bioaccumulation potential increased with increasing carbon-chain length, except for C4. Distinct affinities were observed for specific carbon-chain PFCAs across various tissues, evident from their differential accumulation during both uptake and depuration phases. Specifically, C9 showed a higher affinity for serum and liver, C12 was more prevalent in yolk, C14 was notably abundant in the brain, and C18 was predominant in other tissues. Furthermore, the egg-maternal ratio (EMR) increased with increasing carbon-chain length from C7 to C11 and reached a plateau phase for C12 to C18. Our study also confirmed the key role of phospholipids in the tissue distribution and maternal transfer of long-chain PFCAs. This study sheds light on the interaction between PFCAs and biological tissues and reveals the toxicokinetic factors that influence the bioaccumulation of PFCAs. Further research is needed to identify the specific proteins or components that mediate the tissue-specific affinity for different carbon-chain lengths of PFCAs.
Subject(s)
Chickens , Fluorocarbons , Animals , Female , Bioaccumulation , Tissue Distribution , Chickens/metabolism , Fluorocarbons/metabolism , Carboxylic Acids/metabolism , CarbonABSTRACT
OBJECTIVES: Abnormal expression of long non-coding RNAs (lncRNAs) plays a prominent role in glioma progression. However, the biological function and mechanism of lncRNA DLGAP1 antisense RNA 1 (DLGAP1-AS1) in gliomas are still unknown. METHODS: The authors assessed DLGAP1-AS1 and miR-628-5p expression in glioma tissues and cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and evaluated their effects on glioma cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) using the cell counting kit-8 (CCK-8) assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay, Transwell assay, and western blot, respectively. The expression of DEAD-box helicase 59 (DDX59) was quantified using western blotting, and a dual-luciferase reporter gene assay was performed to detect the interaction between DLGAP1-AS1 and miR-628-5p. RESULTS: The authors observed increased DLGAP1-AS1 expression in glioma tissues and cell lines with higher WHO grades and shorter survival time. DLGAP1-AS1 promoted the proliferation, migration, invasion, and EMT of glioma cells, while miR-628-5p counteracted these effects. The authors identified DLGAP1-AS1 as a molecular sponge of miR-628-5p in glioma cells as the biological functions of DLGAP1-AS1 are partially mediated via miR-628-5p. In addition, DLGAP1-AS1 upregulated DDX59 expression by inhibiting miR-628-5p expression. CONCLUSION: The DLGAP1-AS1/miR-628-5p/DDX59 axis regulates glioma progression.
Subject(s)
Glioma , MicroRNAs , RNA Helicases , RNA, Antisense , RNA, Long Noncoding , Cell Line, Tumor , Cell Proliferation/genetics , DEAD-box RNA Helicases/genetics , DEAD-box RNA Helicases/metabolism , Glioma/genetics , Humans , MicroRNAs/genetics , RNA Helicases/genetics , RNA Helicases/metabolism , RNA, Antisense/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolismABSTRACT
OBJECTIVE: The aim of this study was to explore the ototoxicity of toluene in the early development of zebrafish embryos/larvae. METHODS: Zebrafish were utilized to explore the ototoxicity of toluene. Locomotion analysis, immunofluorescence, and qPCR were used to understand the phenotypes and molecular mechanisms of toluene ototoxicity. RESULTS: The results demonstrated that at 2 mmol/L, toluene induced zebrafish larvae death at 120 hours post fertilization (hpf) at a rate of 25.79% and inhibited the rate of hatching at 72 hpf. Furthermore, toluene exposure inhibited the distance travelled and average swimming velocity of zebrafish larvae while increasing the frequency of movements. As shown by fluorescence staining of hair cells, toluene inhibited the formation of lateral line neuromasts and middle line 1 (Ml 1) neuromasts in 3 days post fertilization larvae in a concentration-dependent manner. Toluene altered the expression level of genes involved in ear development/function in zebrafish, among which the mRNA levels of cd164l2, tekt3, and pcsk5a were upregulated, while the level of otofb was downregulated, according to the qPCR results. CONCLUSION: This study indicated that toluene may affect the development of both the inner ear and lateral line systems in zebrafish, while the lateral line system may be more sensitive to toluene than the inner ear.
Subject(s)
Ear, Inner/drug effects , Lateral Line System/drug effects , Toluene/toxicity , Animals , Ear, Inner/growth & development , Embryo, Nonmammalian/drug effects , Gene Expression Regulation, Developmental/drug effects , Hair Cells, Auditory/drug effects , Hair Cells, Auditory/metabolism , Lateral Line System/growth & development , Locomotion/drug effects , Ototoxicity/etiology , Ototoxicity/pathology , Ototoxicity/physiopathology , ZebrafishABSTRACT
OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody (NAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In total, 605 serum samples from 125 COVID-19 patients (from January 1 to March 14, 2020) varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2. RESULTS: NAbs were detectable approximately 10 days post-onset (dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective. CONCLUSION: We demonstrated that NAb levels vary among all categories of COVID-19 patients. Long-term studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.
Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Adult , Aged , Aged, 80 and over , Female , Humans , Kinetics , Male , Middle Aged , Neutralization Tests , SARS-CoV-2ABSTRACT
Abstract Objectives Abnormal expression of long non-coding RNAs (lncRNAs) plays a prominent role in glioma progression. However, the biological function and mechanism of lncRNA DLGAP1 antisense RNA 1 (DLGAP1-AS1) in gliomas are still unknown. Methods The authors assessed DLGAP1-AS1 and miR-628-5p expression in glioma tissues and cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and evaluated their effects on glioma cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) using the cell counting kit-8 (CCK-8) assay, 5-Ethynyl-2′-deoxyuridine (EdU) assay, Transwell assay, and western blot, respectively. The expression of DEAD-box helicase 59 (DDX59) was quantified using western blotting, and a dual-luciferase reporter gene assay was performed to detect the interaction between DLGAP1-AS1 and miR-628-5p. Results The authors observed increased DLGAP1-AS1 expression in glioma tissues and cell lines with higher WHO grades and shorter survival time. DLGAP1-AS1 promoted the proliferation, migration, invasion, and EMT of glioma cells, while miR-628-5p counteracted these effects. The authors identified DLGAP1-AS1 as a molecular sponge of miR-628-5p in glioma cells as the biological functions of DLGAP1-AS1 are partially mediated via miR-628-5p. In addition, DLGAP1-AS1 upregulated DDX59 expression by inhibiting miR-628-5p expression. Conclusion The DLGAP1-AS1/miR-628-5p/DDX59 axis regulates glioma progression.
ABSTRACT
OBJECTIVE: To explore the operative technique and evaluate the effect of intracranial aneurysms via keyhole approach. METHODS: Fifty-six intracranial aneurysm patients, 23 with anterior communicating artery (AcomA) aneurysm, 29 with posterior communicating artery (PcomA) aneurysm, and 4 with internal carotid artery-posterior communicating artery aneurysm, totally with 58 lesions, were treated by microsurgery, via supraorbital keyhole approach in 22 cases, pterional approach in 18, and transorbital approach in 16. Adjuvant endoscopy was used in 33 patients. RESULTS: Fifty-eight lesions of aneurysm were clipped in all the patients and no one died. No approach-related severe complication occurred. Bilateral PcomA aneurysms in 2 cases were clipped via unilateral keyhole approach. CONCLUSION: It is workable to treat intracranial aneurysms via keyhole approach. Keyhole approach not only reduces the operation-related trauma and shorten the operation time, but also obtains ideal results.