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1.
Environ Sci Technol ; 58(21): 9113-9124, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38743028

ABSTRACT

The antioxidant N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its oxidized quinone product 6PPD-quinone (6PPD-Q) in rubber have attracted attention due to the ecological risk that they pose. Both 6PPD and 6PPD-Q have been detected in various environments that humans cohabit. However, to date, a clear understanding of the biotransformation of 6PPD-Q and a potential biomarker for exposure in humans are lacking. To address this issue, this study presents a comprehensive analysis of the extensive biotransformation of 6PPD-Q across species, encompassing both in vitro and in vivo models. We have tentatively identified 17 biotransformation metabolites in vitro, 15 in mice in vivo, and confirmed the presence of two metabolites in human urine samples. Interestingly, different biotransformation patterns were observed across species. Through semiquantitative analysis based on peak areas, we found that almost all 6PPD-Q underwent biotransformation within 24 h of exposure in mice, primarily via hydroxylation and subsequent glucuronidation. This suggests a rapid metabolic processing of 6PPD-Q in mammals, underscoring the importance of identifying effective biomarkers for exposure. Notably, monohydroxy 6PPD-Q and 6PPD-Q-O-glucuronide were consistently the most predominant metabolites across our studies, highlighting monohydroxy 6PPD-Q as a potential key biomarker for epidemiological research. These findings represent the first comprehensive data set on 6PPD-Q biotransformation in mammalian systems, offering insights into the metabolic pathways involved and possible exposure biomarkers.


Subject(s)
Benzoquinones , Biomarkers , Biotransformation , Environmental Exposure , Environmental Pollutants , Phenylenediamines , Animals , Mice , Environmental Exposure/analysis , Phenylenediamines/blood , Phenylenediamines/metabolism , Phenylenediamines/urine , Benzoquinones/blood , Benzoquinones/metabolism , Benzoquinones/urine , Hydroxylation , Biomarkers/metabolism , Biomarkers/urine , Rubber/chemistry , Male , Young Adult , Adult , Rats , Microsomes, Liver/metabolism , Female , Environmental Pollutants/blood , Environmental Pollutants/metabolism , Environmental Pollutants/urine
2.
Environ Sci Technol ; 58(25): 10910-10919, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38862419

ABSTRACT

With the widespread use of bisphenol A (BPA) analogs, their health risks have attracted attention. The effects of maternal BPA analogs exposure on glucose homeostasis in adult offspring and the underlying fetal origins require further exploration. Herein, we exposed pregnant mice to two types of BPA analogs─BPB and BPAF; we evaluated glucose homeostasis in adult offspring and maternal-fetal glucose transport by testing intraperitoneal glucose tolerance, determining glucose and glycogen contents, conducting positron emission tomography (PET)/computed tomography (CT), detecting expression of placental nutrient transport factors, and assessing placental barrier status. We observed that adult female offspring maternally exposed to BPB and BPAF exhibited low fasting blood glucose in adulthood, with even abnormal glucose tolerance in the BPAF group. This phenomenon can be traced back to the elevated fetal glucose induced by the increased efficiency of placenta glucose transport in late pregnancy. On the other hand, the expression of genes associated with vascular development and glucose transport was significantly altered in the placenta in the BPAF group, potentially contributing to enhanced fetal glucose. These findings provide preliminary insights into potential mechanisms underlying the disturbance of glucose metabolism in adult female offspring mice induced by maternal exposure to BPA analogs.


Subject(s)
Benzhydryl Compounds , Maternal Exposure , Phenols , Female , Animals , Mice , Pregnancy , Phenols/toxicity , Benzhydryl Compounds/toxicity , Glucose/metabolism , Placenta/metabolism , Placenta/drug effects , Fetus/drug effects , Prenatal Exposure Delayed Effects
3.
Biotechnol Bioeng ; 119(9): 2482-2493, 2022 09.
Article in English | MEDLINE | ID: mdl-35680651

ABSTRACT

High value unsaturated fatty acids can be produced by de novo synthesis in microalgal cells, especially via heterotrophic cultivation. Unfortunately, the lipid accumulation of heterotrophic microalgae cannot be improved efficiently in conventional ways. Here we reported heterotrophic Tribonema minus, a promising resource for the production of palmitoleic acid which has increasing demands in health service for patients with metabolic syndrome, as whole-cell biocatalyst to develop a novel way of shifting low value exogenous saturated fatty acids to high value ones. Results showed that myristic acid is the best precursor for whole-cell catalysis; it elevated the lipid content of T. minus to 42.2%, the highest among the tried precursors. The influences of cultivation condition on the utilization of extrinsic myristic acid and lipid accumulation were also determined. Under the optimized condition, the lipid content reached as high as 48.9%. In addition, our findings showed that ~13.0% of C16:1 in T. minus is derived from extrinsic myristic acid, and 30.1% of metabolized precursor is converted into heterologous fatty acids. Thus, a feasible approach for both increasing the value of low value saturated fatty acid by bioconversion and enhancing the lipid accumulation in microalgae is proposed by supplementing extrinsic myristic acid.


Subject(s)
Microalgae , Stramenopiles , Biofuels , Biomass , Catalysis , Fatty Acids/metabolism , Humans , Microalgae/metabolism , Myristic Acids/metabolism
4.
Environ Sci Technol ; 56(12): 8384-8394, 2022 06 21.
Article in English | MEDLINE | ID: mdl-35666658

ABSTRACT

Bisphenol A (BPA) and its analogs are frequently detected in human daily necessities and environmental media. Placental thyroid hormone plays an important role in fetal development. Herein, we followed the adverse outcome pathway (AOP) to explore the toxic mechanisms of BPA and its analogs toward placental thyroid hormone receptor (TR). First, the TOX21 database was used, and the interactions between BPA analogs and the ligand-binding domains (LBDs) of two subtypes of TR (TRα and TRß) were subjected to in silico screening using molecular docking (MD) and molecular dynamics simulation (MDS). Fluorescence spectra and circular dichroism (CD) showed that BPA and its analogs interfere with TRs as a molecular initiation event (MIE), including static fluorescence quenching and secondary structural content changes in TR-LBDs. Key events (KEs) of the AOP, including the toxicity induced in placental chorionic trophoblast cells (HTR-8/SVneo) by an inverted U-shaped dose effect and changes in ROS levels, were tested in vitro. BPA, BPB, and BPAF significantly changed the expression level of TRß, and only BPAF significantly downregulated the expression level of TRα. In conclusion, our study contributes to the health risk assessment of BPA and its analogs regarding placental adverse outcomes (AOs).


Subject(s)
Receptors, Thyroid Hormone , Trophoblasts , Benzhydryl Compounds/toxicity , Female , Humans , Molecular Docking Simulation , Phenols , Placenta/metabolism , Pregnancy , Receptors, Thyroid Hormone/metabolism , Thyroid Hormone Receptors beta , Trophoblasts/metabolism
5.
Environ Res ; 212(Pt B): 113263, 2022 09.
Article in English | MEDLINE | ID: mdl-35430275

ABSTRACT

Placental senescence is a normal physiological process of placenta, while premature placental senescence has been confirmed to be associated with some adverse pregnancy complications. Epidemiological studies indicate that NO2 exposure can aggravate placental senescence which is represented by fibrosis and abnormal telomere homeostasis, etc. In this study, pregnant C57BL/6 mice were exposed to NO2 (2.5 ppm, 5 h/day) daily in a dynamic exposure chamber throughout the gestation period, and were sacrificed at embryonic day 13.5 (E13.5), E15.5 and E18.5. Placenta were harvested and conducted for histopathological examination and telomere evaluation. Our results showed that gestational NO2 exposure significantly aggravated placental fibrosis and calcification, and up-regulated the related bio-markers (connective tissue growth factor (Ctgf) and transforming growth factor-ß1 (Tgf-ß1)) at E18.5. In addition, gestational exposure to NO2 also activated senescence related pathway (p53/p21) at E18.5. Furthermore, gestational NO2 exposure significantly shortened telomere length at E18.5, and the expression of telomere homeostasis regulation genes telomeric repeat binding factor 1 (Trf1), protection of telomeres 1a (Pot1a) and Pot1b were significantly increased while telomerase reverse transcriptase (Tert) was suppressed after NO2 exposure at E13.5 or E18.5, respectively. Importantly, DNA methylation status of the 22nd at E13.5 and 32nd at E18.5 site in sub-telomeric region of chromosome 1 was significantly altered. Based on the above results, our present study indicated that gestational NO2 exposure could lead to premature placental senescence during the late trimester of pregnancy via aggravation of fibrosis and telomere length shortening regulated by telomere regulatory enzyme and DNA methylation.


Subject(s)
Nitrogen Dioxide , Placenta , Telomere Shortening , Animals , Cellular Senescence/genetics , DNA-Binding Proteins/genetics , Female , Fibrosis , Mice , Mice, Inbred C57BL , Nitrogen Dioxide/adverse effects , Placenta/metabolism , Placenta/physiopathology , Pregnancy , Telomere/metabolism
6.
Ecotoxicol Environ Saf ; 246: 114140, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36209526

ABSTRACT

Gestation is a sensitive window to nitrogen dioxide (NO2) exposure, which may disturb fetal lung development and lung function later in life. Animal and epidemiological studies indicated that long noncoding RNAs (lncRNAs) participate in abnormal lung development induced by environmental pollutant exposure. In the present study, pregnant C57BL/6J mice were exposed to 2.5 ppm NO2 (mimicking indoor occupational exposure) or clean air, and lncRNAs expression profiles in the lungs of offspring mice were determined by lncRNA-seq on embryonic day 13.5 (E13.5), E18.5, postnatal day 1 (P1), and P14. The lung histopathology examination of offspring was performed, followed by weighted gene coexpression network analysis (WGCNA), prediction of lncRNAs-target genes, and the biological processes enrichment analysis of lncRNAs. Our results indicated that maternal NO2 exposure induced hypoalveolarization on P14 and differentially expressed lncRNAs showed a time-series pattern. Following WGCNA and enrichment analysis, 2 modules participated in development-related pathways. Importantly, the expressions of related genes were altered, some of which were confirmed to be related to abnormal vascular development and even lung diseases. The research points out that the maternal NO2 exposure leads to abnormal lung development in offspring that might be related to altered lncRNAs expression profiles with time-series-pattern.


Subject(s)
Environmental Pollutants , RNA, Long Noncoding , Animals , Female , Humans , Mice , Pregnancy , Gene Expression Profiling/methods , Lung/metabolism , Maternal Exposure , Mice, Inbred C57BL , Nitrogen Dioxide/toxicity , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism
7.
Genomics ; 113(1 Pt 1): 387-397, 2021 01.
Article in English | MEDLINE | ID: mdl-33326833

ABSTRACT

BACKGROUND: As a class of endogenous non-coding RNAs with closed-loop structure, circular RNAs (circRNAs) are receiving more and more attention. CircRNAs have been reported to be widely expressed in various human cancers and are implicated in tumorigenesis and progression. The present study aimed to systematically evaluate the clinicopathological, diagnostic and prognostic values of circRNAs in lung cancer. METHODS: We searched literature from PubMed, Web of science, Cochrane Library, EMBASE and Ovid online databases up to May 29, 2020. Statistical analyses were undertaken based on Stata 11.0, Meta-DiSc 1.4, and RevMan 5.3 software. RESULTS: Finally, a total of 63 eligible articles were included in our meta-analysis, including 18 studies for diagnosis, 22 studies for prognosis and 57 studies for clinicopathological features. In terms of diagnostic values, circRNAs could discriminate between lung cancer patients and the normal individuals with a relatively high pooled area under the curve (AUC) of 0.83 (95%CI, 0.80-0.86). For the prognostic values, we found that elevated expression of oncogenic circRNAs could predict poor survival outcomes based on multivariate analysis (HR = 2.430, 95%CI = 2.003-2.948, P < 0.001 for OS; HR = 2.228, 95%CI = 1.289-3.853, P = 0.004 for DFS) while tumor-suppressor circRNAs was correlated with better OS in univariate analysis (HR = 0.627, 95%CI = 0.519-0.757, P < 0.001). The pooled results suggested that elevated expression of carcinogenic circRNAs was associated with tumor size (OR = 1.676, 95%CI = 1.209-2.323, P = 0.002), smoking statue (OR = 1.260, 95%CI = 1.062-1.494, P = 0.008), TNM stage (OR = 2.345, 95%CI = 1.617-3.399, P < 0.001), differentiation grade (OR = 1.843, 95%CI = 1.228-2.765, P = 0.003), and lymphatic metastasis (OR = 2.097, 95%CI = 1.482-2.967, P < 0.001). Moreover, the expression of tumor-suppressor circRNAs was related to the improved clinicopathological features (lymphatic metastasis: OR = 0.536, 95%CI = 0.311-0.926, P = 0.025). CONCLUSIONS: Our meta-analysis demonstrated that circRNAs could be used as feasible and important biomarkers for diagnosis, prognosis and clinicopathological features in lung cancer.


Subject(s)
Biomarkers, Tumor/genetics , Lung Neoplasms/genetics , RNA, Circular/genetics , Biomarkers, Tumor/metabolism , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , RNA, Circular/metabolism , Survival Analysis , Tumor Burden
8.
Zhongguo Zhong Yao Za Zhi ; 47(14): 3863-3875, 2022 Jul.
Article in Zh | MEDLINE | ID: mdl-35850845

ABSTRACT

This study investigated the potential active components against cyclooxygenase-2(COX-2) from Trachelospermi Caulisetfolium and explored the pharmacodynamic material basis.A pharmacophore-based virtual screening method was adopted to establish a COX-2 ligands-based HipHop pharmacophore model on the basis of the information on compounds with COX-2 inhibitory activity reported in published research articles.The reported components in Trachelospermi Caulisetfolium were collected to establish the compound library and matched with the pharmacophores.Subsequently, the matched small molecule compounds underwent molecular docking with COX-2 targets(PDB ID: 3 LN1), and the interaction of potential active monomers and COX-2 was further explored by molecular dynamics.The antiepileptic effect of active monomer arctigenin(15) was determined based on the pentylenetetrazole(PTZ)-induced seizure model, and its modulatory effect on the COX-2 level was evaluated.A compound library containing 118 chemical constituents in Trachelospermi Caulisetfolium was established by literature retrieval.The preferred pharmacophore 04 was selected through test set verification for virtual screening of the compound library of Trachelospermi Caulisetfolium.After matching, six potential constituents with COX-2 inhibitory activity were obtained.The interaction of five compounds with COX-2 and COX-1 was analyzed by molecular docking, and 10 ns molecular dynamics was performed on two compounds.Compound 15 could prolong the latent time of PTZ-induced seizures at medium and high doses, improve the anxiety-and depression-like behaviors induced by PTZ, reduce the expression level of COX-2, and decrease the number of COX-2 immuno-posi-tive cells in the hippocampal CA1 region.The results showed that it was reasonable to investigate the components in Trachelospermi Caulisetfolium with COX-2 inhibitory activity based on virtual screening and activity evaluation.


Subject(s)
Anticonvulsants , Cyclooxygenase 2 Inhibitors , Anticonvulsants/pharmacology , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors/chemistry , Cyclooxygenase 2 Inhibitors/pharmacology , Humans , Ligands , Molecular Docking Simulation , Seizures/chemically induced , Seizures/drug therapy
9.
Bioorg Chem ; 108: 104557, 2021 03.
Article in English | MEDLINE | ID: mdl-33376010

ABSTRACT

Succinimides are well recognized heterocyclic compounds in drug discovery which produce diverse therapeutically related applications in pharmacological practices. Researches in medicinal chemistry field have isolated and synthesized succinimide derivatives with multiple medicinal properties including anticonvulsant, anti-inflammatory, antitumor and antimicrobial agents, 5-HT receptor ligands and enzyme inhibitors. Simultaneously, SAR (Structure-Activity Relationship) analysis has been gradually possessed, along with a great deal of derivatives have been derived for potential targets. In this article, we comprehensively summarize the biological activities and SAR for succinimide derivatives, along with the featuring bioactive molecules reported in patents, wishing to provide an overall retrospect and prospect on the succinimide analogues.


Subject(s)
Anti-Infective Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anticonvulsants/pharmacology , Antineoplastic Agents/pharmacology , Enzyme Inhibitors/pharmacology , Succinimides/pharmacology , Anti-Infective Agents/chemistry , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anticonvulsants/chemistry , Antineoplastic Agents/chemistry , Enzyme Inhibitors/chemistry , Humans , Molecular Structure , Succinimides/chemistry
10.
Ecotoxicol Environ Saf ; 207: 111281, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-32919195

ABSTRACT

Epidemiological studies of human and animal experiments indicated that gestational exposure to atmospheric pollutants could be followed by the abnormal placental development. However, the effects of this exposure on the placental transportation for nutrients have not been systematically investigated. In this study, fine particulate matters (PM2.5) samples were collected in Taiyuan and pregnant rodent models were administered with 3 mg/kg b.w. PM2.5 by oropharyngeal aspiration every other day starting on embryonic day 0.5 (E0.5). Then the pregnant mice were sacrificed and their placentas were collected at different time points. The results showed that maternal PM2.5 exposure (MPE) disrupted the expression of proliferating cell nuclear antigen (PCNA) at all time points and inhibited the cell proliferation in placenta. Following that, the capacity for placental nutrient transport was impaired. The changes at E18.5 were observed most significantly, showing the altered mRNA expression of amino acid, long-chain polyunsaturated fatty acid (LCPUFA), glucose and folate transporters. In addition, the glycogen content was elevated at E18.5, and the triglyceride content was increased at E13.5 and E15.5 and decreased at E18.5 in the placenta after MPE. In a word, the adverse effect induced by MPE revealed that MPE led tothe disruption on the nutrient supply to the developing fetus via modulating the abundance of placental nutrient transporters (PNT).


Subject(s)
Air Pollutants/toxicity , Maternal Exposure/adverse effects , Nutrients/metabolism , Particulate Matter/toxicity , Placenta/drug effects , Air Pollutants/metabolism , Amino Acids/metabolism , Animals , Biological Transport , Cell Proliferation/drug effects , Fatty Acids/metabolism , Female , Glucose/metabolism , Glycogen/metabolism , Humans , Maternal-Fetal Exchange/drug effects , Mice , Particulate Matter/metabolism , Placenta/metabolism , Placenta/pathology , Pregnancy
11.
Environ Sci Technol ; 54(1): 316-324, 2020 01 07.
Article in English | MEDLINE | ID: mdl-31872757

ABSTRACT

Lung development continues from the embryonic period to adulthood. Previous epidemiological studies have noted that maternal exposure of atmospheric pollutants during the sensitive windows disturbed the lung development and increased the risk of lung diseases after birth, but the experimental evidence was insufficient. In the present study, we exposed plug-positive mice to PM2.5 (3 mg/kg b.w.) by oropharyngeal aspiration every other day, and intended to test whether maternal PM2.5 exposure affected prenatal lung development in the offspring. First, maternal PM2.5 exposure decreased embryo weight and crown-rump length at E18.5 but not in earlier developmental stages (E0-E16.5). Second, maternal PM2.5 exposure did not prevent lung-bud and tracheal specification, and did not cause abnormalities in branching morphogenesis, distal lung epithelium, and mesenchyme differentiation in earlier stages of lung development (E0-E16.5). However, the exposure significantly disturbed the distal lung epithelium and mesenchyme differentiation of lung, led to reduced intact rings of trachea, and suppressed the expression of lung development-related genes (Nkx2.1, Tbx4, Tbx5, and Sox9) at E18.5. Finally, we found that the exposure not only increased PM2.5-bound metal content (Pb and Cu) but also caused inflammatory response in the placenta, which transmitted from the mother to the fetus and contributed to the developmental abnormalities.


Subject(s)
Fetal Development , Maternal Exposure , Adult , Animals , Female , Fetus , Humans , Lung , Mice , Particulate Matter , Pregnancy
12.
Int J Mol Sci ; 21(6)2020 Mar 18.
Article in English | MEDLINE | ID: mdl-32197393

ABSTRACT

Eukaryotic translation elongation factors are implicated in protein synthesis across different living organisms, but their biological functions in the pathogenesis of cucumber mosaic virus (CMV) and tobacco rattle virus (TRV) infections are poorly understood. Here, we isolated and characterized a cDNA clone, LreEF1A4, encoding the alpha subunit of elongation factor 1, from a CMV-elicited suppression subtractive hybridization library of Lilium regale. The infection tests using CMV remarkably increased transcript abundance of LreEF1A4; however, it also led to inconsistent expression profiles of three other LreEF1A homologs (LreEF1A1-3). Protein modelling analysis revealed that the amino acid substitutions among four LreEF1As may not affect their enzymatic functions. LreEF1A4 was ectopically overexpressed in petunia (Petunia hybrida), and transgenic plants exhibited delayed leaf and flower senescence, concomitant with increased transcription of photosynthesis-related genes and reduced expression of senescence-associated genes, respectively. A compromised resistance to CMV and TRV infections was found in transgenic petunia plants overexpressing LreEF1A4, whereas its overexpression resulted in an enhanced tolerance to salt and drought stresses. Taken together, our data demonstrate that LreEF1A4 functions as a positive regulator in viral multiplication and plant adaption to high salinity and dehydration.


Subject(s)
Cucumovirus/metabolism , Disease Resistance , Lilium/genetics , Peptide Elongation Factors , Petunia , Plant Proteins , Plant Viruses/metabolism , Plants, Genetically Modified , Salt Tolerance , Cucumovirus/genetics , Dehydration/genetics , Dehydration/metabolism , Peptide Elongation Factors/genetics , Peptide Elongation Factors/metabolism , Petunia/genetics , Petunia/metabolism , Petunia/virology , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Viruses/genetics , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolism , Plants, Genetically Modified/virology
13.
Ecotoxicol Environ Saf ; 170: 620-626, 2019 Apr 15.
Article in English | MEDLINE | ID: mdl-30579162

ABSTRACT

Ambient fine particulate matter (PM2.5) is a challenge to public health worldwide. Although increasing numbers of recent epidemiological studies have emphasized the critical role of PM2.5 in promoting respiratory diseases, the precise mechanism behind PM2.5-mediated lung obstruction remains obscure. In the present study, we analyzed lung structure and function and further investigated mitochondrial morphology and transcription-modulated energy metabolism in mice following PM2.5 aspiration. The results showed that PM2.5 exposure reduced pulmonary function and induced severe pathological alterations, including alveolar endothelial disruption and airway obstruction. Based on ultrastructural observations, we also found mitochondrial vacuolation and mitochondrial membrane rupture in alveolar type II epithelial cells. Importantly, the abnormality of mitochondrial structure was coupled with energy metabolism disorders, as evidenced by the decrease in ATP levels, the accumulation of pyruvate and lactate content, and the altered transcription of related genes. Moreover, the reduction in mitochondrial markers, including PGC-1α, NRF-1, and TFAM, were involved in mitochondrial dysfunction. These findings suggest that energy metabolic disorders and mitochondrial dysfunction may be the important contributors to pulmonary injuries in response to PM2.5 exposure, indicating possible targets for protection and therapy in polluted areas.


Subject(s)
Air Pollutants/toxicity , Energy Metabolism/drug effects , Lung Injury/chemically induced , Metabolic Diseases/chemically induced , Mitochondria/drug effects , Particulate Matter/toxicity , Air Pollutants/analysis , Animals , Female , Lung Injury/metabolism , Lung Injury/pathology , Metabolic Diseases/metabolism , Metabolic Diseases/pathology , Mice , Mice, Inbred C57BL , Mitochondria/metabolism , Mitochondria/ultrastructure , Particle Size , Particulate Matter/analysis , Respiratory Function Tests
14.
Chem Biodivers ; 16(3): e1800589, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30793831

ABSTRACT

Herbaceous peony has been widely cultivated in China due to its substantial ornamental and medicinal value. In the present study, the phenotypic characteristics, total fatty acid (FA) content, and nine FA compositions of herbaceous peony seeds from 14 populations belonging to six species and one subspecies were determined by normal test and gas chromatography/mass spectrometry (GC/MS). The results showed that the phenotypic characteristics of seeds varied dramatically among species. The concentrations of five major FAs in seed oils were as follows: linoleic acid (173.95-236.51 µg/mg), linolenic acid (227.82-302.71 µg/mg), oleic acid (135.32-208.81 µg/mg), stearic acid (6.52-11.7 µg/mg), and palmitic acid (30.67-47.64 µg/mg). Correlation analysis demonstrated that oleic acid had the highest partial correlation coefficient with total FAs and might be applied to develop a model of phenotypic characteristics. FAs were significantly influenced by the following environmental factors: latitude, elevation, and annual average temperature. Based on the FA levels in the seed oils, clustering analysis divided 14 populations into two clusters. It was found that the average contents of oleic acid, linoleic acid, and total FAs in cluster I (147.16 µg/mg, 200.31 µg/mg, and 671.24 µg/mg, respectively) were significantly lower than those in cluster II (196.65 µg/mg, 220.16 µg/mg, and 741.78 µg/mg, respectively). Cluster I was perfectly consistent with subsect. Foliolatae, while cluster II was in good agreement with subsect. Dissectifoliae. Therefore, the FA composition of wild herbaceous peony seed oil might be used as a chemotaxonomic marker.


Subject(s)
Fatty Acids/analysis , Paeonia/chemistry , Plant Extracts/analysis , Seeds/chemistry , China , Paeonia/classification , Phenotype , Species Specificity
15.
Arch Toxicol ; 92(4): 1563-1579, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29417167

ABSTRACT

Maternal exposure to nitrogen dioxide (NO2) poses a risk for morbidity and mortality in infantile congenital heart diseases and even adult cardiovascular diseases. However, the experimental evidence supporting these effects is insufficient, and the related regulatory mechanisms are unknown. In the present study, we aimed to determine whether maternal NO2 exposure causes cardiac hypertrophy-related consequences in offspring, and if so, how these adverse effects occur in the postnatal heart. The results indicate that in mice, maternal NO2 exposure causes cardiac hypertrophy in male offspring. This altered phenotype was accompanied by increased expression of atrial natriuretic peptide, B-type natriuretic peptide, bone morphogenetic protein 10 and ß-myosin heavy chain and elevated activities of cardiomyocyte injury markers, including serum glutamate-oxaloacetate transaminase, lactate dehydrogenase and kinases creatine phosphokinase (CK-MB) in serum. The cardiac-specific transcription factor Csx/Nkx2.5 played an important role in the induction of cardiac hypertrophy and cardiomyocyte injury, and the action was associated with ROS-HIF-1α transcriptional regulation and DNA hypomethylation modification.


Subject(s)
Cardiomegaly/chemically induced , Homeobox Protein Nkx-2.5/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Maternal Exposure , Nitrogen Dioxide/toxicity , Reactive Oxygen Species/metabolism , Animals , Aspartate Aminotransferases/blood , Atrial Natriuretic Factor/blood , Biomarkers/blood , Bone Morphogenetic Proteins/blood , Cardiomegaly/genetics , Creatine Kinase/blood , DNA Methylation , Female , Gene Expression Regulation , Humans , L-Lactate Dehydrogenase/blood , Male , Mice , Natriuretic Peptide, Brain/blood , Pregnancy , Ventricular Myosins/blood
16.
Part Fibre Toxicol ; 14(1): 34, 2017 08 29.
Article in English | MEDLINE | ID: mdl-28851397

ABSTRACT

BACKGROUND: PM2.5 (particulate matter ≤ 2.5 µm) is one of the leading environmental risk factors for the global burden of disease. Whereas increasing evidence has linked the adverse roles of PM2.5 with cardiovascular and respiratory diseases, limited but growing emerging evidence suggests that PM2.5 exposure can affect the nervous system, causing neuroinflammation, synaptic dysfunction and cognitive deterioration. However, the molecular mechanisms underlying the synaptic and cognitive deficits elicited by PM2.5 exposure are largely unknown. METHODS: C57BL/6 mice received oropharyngeal aspiration of PM2.5 (1 and 5 mg/kg bw) every other day for 4 weeks. The mice were also stereotaxically injected with ß-site amyloid precursor protein cleaving enzyme 1 (ß-secretase, BACE1) shRNA or LV-miR-574-5p lentiviral constructs in the absence or presence of PM2.5 aspiration at 5 mg/kg bw every other day for 4 weeks. Spatial learning and memory were assessed with the Morris water maze test, and synaptic function integrity was evaluated with electrophysiological recordings of long-term potentiation (LTP) and immunoblot analyses of glutamate receptor subunit expression. The expression of α-secretase (ADAM10), BACE1, and γ-secretase (nicastrin) and the synthesis and accumulation of amyloid ß (Aß) were measured by immunoblot and enzyme-linked immunosorbent assay (ELISA). MicroRNA (miRNA) expression was screened with a microRNA microarray analysis and confirmed by real-time quantitative reverse transcription PCR (qRT-PCR) analysis. Dual-luciferase reporter gene and chromatin immunoprecipitation (ChIP) analyses were used to detect the binding of miR-574-5p in the 3'UTR of BACE1 and NF-κB p65 in the promoter of miR-574-5p, respectively. RESULTS: PM2.5 aspiration caused neuroinflammation and deteriorated synaptic function integrity and spatial learning and memory, and the effects were associated with the induction of BACE1. The action was mediated by NF-κB p65-regulated downregulation of miR-574-5p, which targets BACE1. Overexpression of miR-574-5p in the hippocampal region decreased BACE1 expression, restored synaptic function, and improved spatial memory and learning following PM2.5 exposure. CONCLUSIONS: Taken together, our findings reveal a novel molecular mechanism underlying impaired synaptic and cognitive function following exposure to PM2.5, suggesting that miR-574-5p is a potential intervention target for the prevention and treatment of PM2.5-induced neurological disorders.


Subject(s)
Air Pollutants/toxicity , Cognitive Dysfunction/chemically induced , MicroRNAs/metabolism , NF-kappa B/metabolism , Particulate Matter/toxicity , Synaptic Potentials/drug effects , Animals , Cognitive Dysfunction/genetics , Cognitive Dysfunction/metabolism , Gene Expression Regulation/drug effects , Hippocampus/drug effects , Hippocampus/metabolism , Inhalation Exposure/analysis , Maze Learning/drug effects , Mice, Inbred C57BL , MicroRNAs/genetics , Particle Size , Spatial Memory/drug effects
17.
J Environ Sci (China) ; 62: 145-153, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29289286

ABSTRACT

In light of the accelerated aging of the global population and the deterioration of the atmosphere pollution, we sought to clarify the potential mechanisms by which fine particulate matter (PM2.5) can cause cognitive impairment and neurodegeneration through the alteration of mitochondrial structure and function. The results indicate that PM2.5 inhalation reduces ATP production by disrupting the aerobic tricarboxylic acid cycle and oxidative phosphorylation, thereby causing the hypophosphorylation of tau in the cortices of middle-aged mice. Furthermore, excessive reactive oxygen species generation was involved in the impairment. Interestingly, these alterations were partially reversed after exposure to PM2.5 ended. These findings clarify the mechanism involved in mitochondrial abnormality-related neuropathological dysfunction in response to atmospheric PM2.5 inhalation and provide an optimistic sight for alleviating the adverse health outcomes in polluted areas.


Subject(s)
Air Pollutants/toxicity , Brain/drug effects , Energy Metabolism/drug effects , Particulate Matter/toxicity , Air Pollutants/analysis , Animals , Brain/physiology , Mice , Particulate Matter/analysis , Phosphorylation/drug effects
18.
Environ Toxicol ; 31(12): 1996-2005, 2016 Dec.
Article in English | MEDLINE | ID: mdl-26417707

ABSTRACT

SO2 , NO2 , and PM2.5 are typical air pollutants produced during the combustion of coal. Increasing evidence indicates that air pollution has contributed to the development and progression of heart-related diseases over the past decades. However, little experimental data and few studies of SO2 , NO2 , and PM2.5 co-exposure in animals exist; therefore, the relevant mechanisms underlying this phenomenon are unclear. An important characteristic of air pollution is that co-exposure persists at a low concentration throughout a lifetime. In the present study, we treated adult mice with SO2 , NO2 , and PM2.5 at various concentrations (0.5 mg/m3 SO2 , 0.2 mg/m3 NO2 6 h/d, with intranasal instillation of 1 mg/kg PM2.5 every other day during these exposures; or 3.5 mg/m3 SO2 , 2 mg/m3 NO2 6 h/d, and 10 mg/kg PM2.5 for 28 d). Blood pressure (BP), heart rate (HR), histopathological damage, and inflammatory and endothelial cytokines in the heart were assessed. The results indicate that co-exposure caused endothelial dysfunction by elevating endothelin-1 (ET-1) expression and repressing the endothelial nitric oxide synthase (eNOS) level as well as stimulating the inflammatory response by increasing the levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Additionally, these alterations were confirmed by histological staining. Furthermore, we observed decreased BP and increased HR after co-exposure. Our results indicate that co-exposure to SO2 , NO2 , and PM2.5 may be a major risk factor for cardiac disease and may induce injury to the hearts of mammals and contribute to heart disease. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1996-2005, 2016.


Subject(s)
Air Pollutants/toxicity , Endothelium, Vascular/drug effects , Nitrogen Dioxide/toxicity , Particulate Matter/toxicity , Sulfur Dioxide/toxicity , Animals , Blood Pressure/drug effects , Cyclooxygenase 2/metabolism , Endothelin-1/metabolism , Endothelium, Vascular/metabolism , Heart Rate/drug effects , Inflammation/chemically induced , Inflammation/metabolism , Interleukin-6/metabolism , Male , Mice, Inbred C57BL , Myocardium/metabolism , Myocardium/ultrastructure , Nitric Oxide Synthase Type III/metabolism , Tumor Necrosis Factor-alpha/metabolism
19.
Environ Res ; 138: 416-24, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25791864

ABSTRACT

Recent epidemiological literatures imply that NO2 is a potential risk factor of neurological disorders. Whereas, the pathogenesis of various neurological diseases has been confirmed correlate to mitochondrial dysfunction, and mitochondria play the crucial roles in energy metabolism, free radicals production and apoptosis triggering in response to neuronal injury. Therefore, to clarify the possible mechanisms for NO2-induced neurotoxicity, in the present study, we investigated the possible effects of acute NO2 inhalation (5, 10 and 20mg/m(3) with 5h/day for 7 days) on energy metabolism and biogenesis in rat cortex, mainly including mitochondrial ultrastructure, mitochondrial membrane potential, cytochrome c oxidase activity, cytochrome c oxidase (CO) and ATP synthase subunits, ATP content, and transcription factors. The results showed that NO2 exposure induced mitochondrial morphological changes in rat cortex, and the alteration was coupled with the abnormality of mitochondrial energy metabolism, including decreased respiratory complexes, reduced ATP production and increased production of ROS. Also, increased ROS in turn caused mitochondrial membrane damage, energy production defect and mitochondrial biogenesis inhibition. It suggests the significantly damaged mitochondrial energy metabolism and impaired biogenesis in rat brain after NO2 exposure, and provides a new understanding of the pathophysiological mechanisms of NO2-induced neurological disorders.


Subject(s)
Air Pollutants/toxicity , Brain Injuries/chemically induced , Brain/drug effects , Energy Metabolism/drug effects , Inhalation Exposure , Mitochondria/drug effects , Nitrogen Dioxide/toxicity , Animals , Dose-Response Relationship, Drug , Male , Mitochondria/enzymology , Mitochondria/physiology , Mitochondria/ultrastructure , Rats , Rats, Wistar
20.
Bioresour Technol ; 406: 131062, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38964514

ABSTRACT

Acquiring lipid-producing strains of Saccharomyces cerevisiae is necessary for producing high-value palmitoleic acid. This study sought to generate oleaginous S. cerevisiae mutants through a combination of zeocin mutagenesis and fluorescence-activated cell sorting, and then to identify key mutations responsible for enhanced lipid accumulation by multi-omics sequencing. Following three consecutive rounds of mutagenesis and sorting, a mutant, MU310, with the lipid content of 44%, was successfully obtained. Transcriptome and targeted metabolome analyses revealed that a coordinated response involving fatty acid precursor biosynthesis, nitrogen metabolism, pentose phosphate pathway, ethanol conversion, amino acid metabolism and fatty acid ß-oxidation was crucial for promoting lipid accumulation. The carbon fluxes of acetyl-CoA and NADPH in lipid biosynthesis were boosted in these pathways. Certain transcriptional regulators may also play significant roles in modulating lipid biosynthesis. Results of this study provide high-quality resource for palmitoleic acid production and deepen the understanding of lipid synthesis in yeast.


Subject(s)
Lipids , Mutagenesis , Saccharomyces cerevisiae , Fatty Acids/metabolism , Fatty Acids, Monounsaturated , Flow Cytometry , Lipid Metabolism , Lipids/biosynthesis , Metabolome , Multiomics , Mutation , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae/genetics , Transcriptome/genetics
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