BIOCHEMICAL GENETICS
·
2020
·Vol. 58
·期 4
·551-565
·
IF 2.027
Xie Shaolin,Zhou Aiguo,Feng Yongyong,Zhang Yue,Li Junyi,Sun Zhuolin,Fan Lanfen,Zou Jixing
Cytochrome P4501A (CYP1A) has been used as a specific biomarker for monitoring water contamination such as PAHs, PCBs and dioxins. In the present study, the cyp1a gene of Gambusia affinis was cloned and sequenced and their expressions under PAHs exposure were characterized. The newly identified cyp1a encodes a protein with 521 amino acids that shared 96–80% identity with other Cyprinodontiformes fishes. RT-PCR analysis revealed that the basal mRNA level of cyp1a was highly expressed in liver and intestine. The expression level of cyp1a was significantly induced by exposure to 100 μg/L 3, 4-Benzopyrene (BaP) for 5 days in the muscle, testis, brain, liver and intestine of adult male fish. Except in the testis, the induced mRNA level of cyp1a ultimately decreased after prolonging the exposure time to 25 days. As for testis, the induced mRNA level of cyp1a was maintained at a high level during the entire exposure time under 100 μg/L BaP exposure. Furthermore, the expression of cyp1a increased with exposure time under a relatively low exposure concentrations 1 μg/L. Regarding the effects of other PAHs, D(a,h)A, BbF, and BaA showed a statistically significant effect of induction on mRNA level of cyp1a in the muscle, testis, brain, liver and intestine.
研究领域:
环境科学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Natural Product Communications
·
2019
·
IF 0.554
Keling Cheng,Xuan Zeng,Hao Wu,Weiwei Su,Weiyang Fan,Yang Bai,Hongliang Yao,Peibo Li
Naringin (NRG) is a common dietary flavonoid in citrus fruits and has been documented to possess multiple pharmacological activities, including anti-oxidant, anti-inflammatory, and neuroprotective effects. Naringin is frequently consumed in combination with common clinical drugs. To date, the effects of NRG on cytochrome P450 enzymes have not been fully investigated yet. In this study, the activities of hepatic CYP1A2, CYP2D2, CYP2C9, CYP2C19, and CYP2E1 in rats after the continuous oral administration of NRG (50 and 500 mg/kg) were evaluated using cocktail probe-drug method. The concentrations of 5 probe drugs (phenacetin, dextromethorphan, diclofenac sodium, omeprazole, and chlorzoxazone) in rat plasma were simultaneously determined with a validated HPLC-MS/MS (high performance liquid chromatography-tandem mass spectrometry) method and then used to calculate corresponding pharmacokinetic parameters. Compared with the control group, the AUC(0-t), AUC(0-∞), t 1/2, and C max of each probe drug in treatment groups showed no significant differences. Meanwhile, fluorescence quantitative polymerase chain reaction (FQ-PCR) analysis revealed that NRG did not significantly affect the mRNA expressions of genes CYP1a2, CYP2d2, CYP2c6, CYP2c11, and CYP2e1 in rat liver. Based on these results, it could be concluded that NRG showed no significant effects on the activities and mRNA expressions of tested CYP450 in rats.
研究领域:
药理学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
·
2023
·
IF 3.5
Peng-Cheng Xu,Chang-Chun Song,Xiao-Ying Tan,Tao Zhao,Chong-Chao Zhong,Jie-Jie Xu,Yu-Feng Song,Zhi Luo
Background Iron is an essential metal element for organisms, whose metabolism is regulated by many genes and also dietary iron sources. However, the characterization, distribution and the responses of iron metabolism-related genes to different iron sources were not clear in fish. Methods The full-length cDNA sequences of fifteen iron metabolism-relevant genes ( tf , tfr1 , hp , fpn1 , ho1 , ho2 , tfr2 , hjv , hepcidin , fth , ftl , ftm , irp1 , irp2 and hif2α .) were obtained via 3′ and 5′ RACE PCR from yellow catfish, a widely distributed freshwater teleost in China and other Asian countries. Their molecular characterizations were analyzed via the bioinformatic methods. Real-time quantitative PCR was used to explore their mRNA distribution in nine tissues. Their mRNA expression responses in four tissues (heart, brain, kidney and gill) were explored in yellow catfish fed diets with five iron sources, including ferrous sulfate (FeSO 4 ), ferrous bisglycinate (Fe-Gly), ferrous chloride (FeCl 2 ), ferric citrate (Fe-CA) and ferric oxide nanoparticles (Fe 2 O 3 NPs). Results Compared with mammals and other teleost, these members shared similar domains. Their mRNAs were expressed in nine tested tissues, but mRNA levels varied. Yellow catfish fed the diets containing Fe-Gly and Fe 2 O 3 NPs had higher iron contents in heart, brain, kidney and gill. Meantime, different dietary iron sources addition affected their mRNA expression differentially in brain, heart, kidney and gill. It should be pointed out that only three biological replicate tanks were used in the present feeding treatment , and more biological replicate tanks (more than five) should be emphasized in further researches. Conclusion Taken together, our study identified fifteen iron metabolism-relevant genes, explored their mRNA expression in nine tissues, and their mRNA expression in the responses to different dietary iron sources in four tissues, indicating their important regulatory function in iron metabolism and homeostasis.
研究领域:
水产养殖
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分子生物学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular & Cellular Toxicology
·
2017
·Vol. 13
·期 1
·59-64
·
IF 1.25
Chen Jiahong,Zhang Hang,Aniagu Stanley,Jiang Yan,Chen Tao
Trichloroethylene (TCE) had been shown to induce aberrant DNA methylation changes in mouse liver, which could be critical in the development of hepatocellular carcinoma. To understand the effect of methionine, a methyl donor, on TCE-induced mouse liver cancer, we exposed B6C3F1 mice to TCE in the presence or absence of methionine. We found that supplementation with methionine attenuated the TCE-induced hypo- and hyper-methylation status of Cdkn1a and Ihh in mouse liver, respectively. The TCE-induced mRNA expression changes of Cdkn1a, Ihh and Jun were also alleviated by methionine. However, methionine supplementation accelerated the TCE-induced mRNA over-expression of Mki67, and enhanced the TCE-induced mRNA down-regulation of Dnmt3a and Tet2. In summary, our results showed that methionine could attenuate at least part of the TCE-induced DNA methylation changes, but the additional gene expression changes induced by supplementary of methionine does not support the assumption that methionine could prevent TCE-induced liver carcinogenesis.
研究领域:
毒理学
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Xuanjun Guo,Ruihua Zhang,Qian Jin,Niannian Cao,Jingjing Shi,Xingxing Zong,Xuejun Chen,Chen Wang,Xuefeng Li,Sen Pang,Liqin Li
Azoxystrobin, a strobilurin widely used to control rice diseases, has raised concerns about possible adverse effects on aquatic ecosystems. At present, very little is known about the effects of azoxystrobin on courtship and aggressive behavior and the potential underlying mechanisms. In the present study, after exposing adult male and female zebrafish to worst-case scenario concentrations of azoxystrobin (0, 2 μg/L, 20 μg/L, and 200 μg/L) for 42 d, we observed a decrease in courtship behavior and an increase in aggressive behavior in both male and female zebrafish. In addition, to elucidate the molecular mechanism of the behavioral effects of azoxystrobin, we quantified the changes in the concentrations of kisspeptin, 5-HT, GnIH, and their corresponding receptor mRNA expression in the brain. The results showed that 200 μg/L azoxystrobin decreased the concentrations of kisspeptin and increased the concentration of GnIH in both male and female zebrafish brain. In addition, azoxystrobin also significantly reduced 5-HT concentration in female zebrafish brain. Further investigation revealed that altered courtship and aggressive behavior were associated with the expression levels of genes (kiss1, kiss2, gnrh3, gnrhr3, 5ht1a, and 5ht2a) involved in kisspeptin-GnIH signaling pathway. In conclusion, our study suggested that azoxystrobin may impair courtship and aggressive behavior in zebrafish by interfering with the kisspeptin-GnIH signaling pathway, which may have more profound effects on natural zebrafish populations.
研究领域:
环境毒理学
·
行为生物学
·
神经内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2024
·Vol. 27
·期 5
·1-8
·
IF 2.4
Yunyan Tang,Hongfang Li,Jianhua Tang,Lei Hu,Feifei Ma,Yanmiao Liu,Fushan Tang
Total saikosaponins (TSS) form a group of chemically and biologically active components that can be extracted from Bupleurum, with reported antidepressive, anti‑inflammatory, antiviral, antiendotoxin, antitumor, anti‑pulmonary fibrosis and anti‑gastric ulcer effects. Bupleurum or TSS is frequently utilized in clinical practice alongside other medications (such as entecavir, lamivudine, compound paracetamol and amantadine hydrochloride capsules), leading to an increased risk of drug‑drug interactions. The cytochrome P450 (CYP) family serves a critical role in the metabolism of numerous essential drugs (such as tamoxifen, ibuprofen and phenytoin), where the majority of drug interactions involve CYP‑mediated metabolism. It is therefore essential to understand the effects of key components of Bupleurum on CYPs when administering combination therapies containing TSS or Bupleurum. The present study aimed to investigate the effects of TSS on the mRNA and protein expression of CYP3A4 and CYP1A2 in HepaRG cells. The effects of TSS on the survival of HepaRG cells was investigated using the Cell Counting Kit‑8 (CCK‑8) method. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot (WB) analysis were used to assess the effects of different concentrations of TSS (0, 5, 10 and 15 µg/ml) on CYP3A4 and CYP1A2 mRNA and protein expression in HepaRG cells. Based on the CCK‑8 assay results, it was observed that the cell viability remained above 80% when treated with 1, 5, 10 and 15 µg/ml TSS. Although there was a statistically significant reduced cell viability at TSS concentrations of 10 and 15 µg/ml compared with the control group, the findings indicated that TSS did not exhibit notable cytotoxic effects at these concentrations. Furthermore, RT‑qPCR results revealed that compared with those in the control group, TSS at concentrations of 10 and 15 µg/ml reduced CYP3A4 mRNA expression but increased CYP1A2 mRNA expression in HepaRG cells at concentrations of 15 µg/ml. WB analysis found that TSS at concentrations of 10 and 15 µg/ml downregulated CYP3A4 protein expression in HepaRG cells while increasing CYP1A2 protein expression at concentrations of 15 µg/ml. Results in the present study suggest that TSS can inhibit CYP3A4 mRNA and protein expression, but exerts opposite effects on their CYP1A2 counterparts. These findings suggest that it is necessary to consider drug interactions between clinical preparations containing TSS or Bupleurum and drugs metabolized by CYP3A4 and CYP1A2 to avoid potential adverse drug reactions in clinical practice.
研究领域:
药理学
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分子生物学
·
毒理学
·
药物代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COMPARATIVE NEUROLOGY
·
2022
·Vol. 531
·期 2
·294-313
·
IF 3.028
Xulin Li,Gaoyang Zhao,Hongren Huang,Jialin Ye,Junfeng Xu,Yuan Zhou,Xiaojuan Zhu,Liping Wang,Feng Wang
Many brain functions that underlie behavior, cognition, and emotions vary with age, as does susceptibility to neuropsychological disorders. The expression of specific genes that are involved in these functions, such as the genes encoding for oxytocin, its receptors, and apolipoprotein D, varies with age across different brain regions. The cannabinoid 1 receptor (CB 1 R) is one of the most widely spread G-protein coupled receptors in the central nervous system and is increasingly recognized for its important contribution to various brain functions. Although changes in CB 1 R expression with age have been reported in the male mouse brain, they have not been well investigated in the female brain. Here, we used fluorescence in situ hybridization to target CB 1 R mRNA in the whole brains of female C57BL/6J mice aged 4, 6, 12, 52 (12 months) and 86 weeks (20 months), and quantified CB 1 R-positive cells in 36 brain regions across the whole brain. The results showed that CB 1 R-positive cells number changed with age. Specifically, CB 1 R expression increased with age in some subregions of the cortex, decreased with age in the lateral septal area, and reached its lowest level at 52 weeks in the thalamus, hypothalamus, and hindbrain subregions. Cluster analysis revealed that some brain regions shared similar temporal characteristics in CB 1 R-positive cell number across the lifespan. Our results provide evidence that investigation of the neural basis of age-related characteristics of female brain functions is not only warranted but required.
研究领域:
神经科学
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分子生物学
·
衰老
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Genetics
·
2021
·
IF 4.599
Peng Yi,Xiongfeng Xu,Jiawei Yao,Bo Qiu
Objectives Transcriptional changes in cartilage can impact function by causing degradation such as that which occurs during the development of osteoarthritis (OA). Epigenetic regulation may be a key factor leading to transcriptional changes in OA. In this study, we performed a combined analysis of DNA methylation and gene expression microarray datasets and identified key transcription factors (TFs) central to the regulation of gene expression in OA. Methods A DNA methylation profile dataset (GSE63106) and a gene expression profiling dataset (GSE114007) were extracted from the Gene Expression Omnibus (GEO). We used ChAMP methylation analysis and the Limma package to identify differentially methylation genes (DMGs) and differentially expressed genes (DEGs) from normal and human knee cartilage samples in OA. Function enrichment analysis of DMGs was conducted using the DAVID database. A combined analysis of DEGs and DMGs was conducted to identify key TFs in OA. We then validated the mRNA expression of selected TFs in normal and OA cartilage by RT-qPCR. Primary chondrocytes were cultured and treated with the DNA methylation inhibitor 5-Aza-2-deoxycytidine (5-Aza) for functional validation. Results We identified 2,170 differential methylation sites (DMS) containing 1005 genes and 1986 DEGs between normal human and OA cartilage. Functional analysis of DMGs revealed that focal adhesion, extracellular matrix (ECM)-receptor interactions, the PI3K-Akt signaling pathway, and the FoxO signaling pathway were involved in OA. Integrated analysis showed a subset of 17 TFs. Four TFs (ELF3, SOX11, RARA, and FOXD2) were validated. RT-qPCR results showed the mRNA expression of SOX11, RARA, and FOXD2 were consistent with the results from the mRNA expression data. However, the expression of ELF3 could not be validated. Upon 5-Aza-2′-deoxycytidine (5-Aza) treatment, the mRNA levels of ELF3 and SOX11 were down-regulated, whilst RARA was up-regulated, and FOXD2 showed no significant change in expression level. Conclusions the effect of DNA methylation on the transcriptional regulation is related to the distribution of methylated sites across the genome. Epigenetic studies on the positions of DMS in transcriptional units can inform a better understanding of the function of DNA methylation and its transcription regulation.
研究领域:
分子生物学
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表观遗传学
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风湿病学
·
骨关节炎研究
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转录调控
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生物信息学
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软骨生物学
✓ 已验证
DOI
高影响因子
Drug Design Development and Therapy
·
2020
·
IF 3.216
Hongfang Li,Yunyan Tang,Yang Wang,Weipeng Wei,Chengchen Yin,Fushang Tang
Background Bupleurum is one of the most important traditional Chinese medicines and an ingredient in many compound preparations. It is widely used together with other drugs in clinical practice, and thus there is great potential for drug–drug interactions. Saikosaponin D (SsD) is a major bioactive triterpenoid saponin extracted from Bupleurum with anti-inflammatory, anticancer, antioxidative, and antihepatic fibrosis effects. Effects of the main components of Bupleurum on cytochromes P450 (CYPs) need to be clarified in the clinical application of combination therapies of formulations containing SsD or Bupleurum . Purpose This study aimed to investigate the effects of SsD on the CYP1A2 and CYP2D6 mRNAs, protein expression, and relative enzyme activities in HepaRG cells. Methods HepaRG cells were cultured with SsD at concentrations of 0.5, 1, 5 and 10 μM for 72 hours. mRNA and protein expression of CYP1A2 and CYP2D6 were analyzed with real-time PCR and Western blot analysis. Relative enzyme activities were analyzed with HPLC based on consumption of the specific probe substrate. Results SsD significantly induced expression of mRNA and increased relative activity of CYP1A2 in HepaRG cells after the cells had been treated with SsD at concentrations of 1, 5 and 10 μM. SsD also induced protein expression of CYP1A2 at concentrations of 5 and 10 μM. SsD exhibited an inductive effect on CYP2D6 mRNA and protein expression, while increasing the relative activity of CYP2D6 at concentrations of 5 and 10 μM. Conclusion This study is the first to investigate the effect of SsD on CYP1A2 and CYP2D6 in HepaRG cells, and the results may provide some useful information on potential drug–drug interactions related to clinical preparations containing SsD or Bupleurum .
研究领域:
药理学
·
毒理学
·
分子生物学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aging-US
·
2024
·
IF 3.9
Guang Wang,Pei Li,Si-Wei Su,Rui Xu,Zi-Ye Huang,Tong-Xin Yang,Jiong-Ming Li
Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition with painful bladder. At present, the pathogenesis of IC/BPS is still unknown. Quercetin (QCT) is a kind of natural flavonoid with wide sources and multiple biological activities. The purpose of this study was to explore the effects of QCT on mRNA expression and related regulatory signal pathways in IC model rats. Methods: LL-37 was used to induce the IC/BPS model rats. 20 mg/kg QCT was injected intraperitoneally into IC/BPS rats. ELISA, HE, Masson and TB staining were used to evaluate the level of inflammation and pathology. The concentration of QCT in rats was detected by HPLC. The mRNA sequencing was used to detect the differentially expressed (DE) mRNA in each group. The over-expression experiment of Lpl was carried out in IC/BPS model rats. Results: QCT treatment significantly decreased the level of MPO, IL-1β, IL-6 and TNF-α induced by LL-37 in rats, and alleviated bladder injury and mast cell degranulation. There were significant differences in mRNA sequencing data between groups, and the hub gene Lpl were screened by Cytohubba. The expression of Lpl was downregulated in IC/BPS rats. QCT intervention promoted Lpl expression. Overexpression of Lpl reduced the bladder injury induced by LL-37, increased GAG level and decreased the expression of MPO, IL-1β, IL-6 and TNF-α. Conclusion: In this study, we provided the DE mRNA in IC/BPS rats treated with QCT, the signaling pathways for DE enrichment, screened out the hub genes, and revealed that Lpl overexpression alleviated IC/BPS model rats.
研究领域:
药理学
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分子生物学
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生物信息学
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泌尿学
✓ 已验证
DOI
PubMed
高影响因子
Nanomaterials
·
2023
·Vol. 13
·期 11
·1779
·
IF 5.3
Shunyu Zhang,Jinxia Li,Liang Yan,Yue You,Feng Zhao,Jixing Cheng,Limin Yang,Yanqi Sun,Qingchao Chang,Ru Liu,Yunhui Li
Telomerase is constitutively overexpressed in the majority of human cancers and telomerase inhibition provides a promising broad-spectrum anticancer therapeutic strategy. BIBR 1532 is a well-known synthetic telomerase inhibitor that blocks the enzymatic activity of hTERT, the catalytic subunit of telomerase. However, water insolubility of BIBR 1532 leads to low cellular uptake and inadequate delivery and thus, limits its anti-tumor effects. Zeolitic imidazolate framework-8 (ZIF-8) is considered as an attractive drug delivery vehicle for improved transport, release and anti-tumor effects of BIBR 1532. Herein, ZIF-8 and BIBR[email protected]were synthesized, respectively, and the physicochemical characterizations confirmed the successful encapsulation of BIBR 1532 in ZIF-8 coupled with an improved stability of BIBR 1532. ZIF-8 could alter the permeability of lysosomal membrane probably by the imidazole ring-dependent protonation. Moreover, ZIF-8 encapsulation facilitated the cellular uptake and release of BIBR 1532 with more accumulation in the nucleus. BIBR 1532 encapsulation with ZIF-8 triggered a more obvious growth inhibition of cancer cells as compared with free BIBR 1532. A more potent inhibition on hTERT mRNA expression, aggravated G0/G1 arrest accompanied with an increased cellular senescence were detected in BIBR[email protected]cancer cells. Our work has provided preliminary information on improving the transport, release and efficacy of water-insoluble small molecule drugs by using ZIF-8 as a delivery vehicle.Keywords:ZIF-8;drug loading;transport;protonation effect;telomerase inhibitor
研究领域:
药学
·
癌症研究
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药物递送系统
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2024
·
IF 2.9
Yifei Shen,Jie Liu,Bingyi Yao,Yuanjin Zhang,Shengbo Huang,Chenmeizi Liang,Junze Huang,Yu Tang,Xin Wang
Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, which can cause serious complications and gradually increase the mortality rate. However, the effects of NAFLD on drug-metabolizing enzymes and transporters remain unclear, which may cause some confusion regarding patient medication. In this study, a NAFLD rat model was constructed by feeding rats with methionine and choline deficiency diets for 6 weeks, and the mRNA and protein levels of drug-metabolizing enzymes and transporter were analyzed by real-time fluorescent quantitative PCR and Western blot, respectively. The activity of drug-metabolizing enzymes was detected by cocktail methods. In the NAFLD rat model, the mRNA expression of phase I enzymes, phase II enzymes, and transporters decreased. At the protein level, only CYP1A1, CYP1B1, CYP2C11, and CYP2J3 presented a decrease. In addition, the activities of CYP1A2, CYP2B1, CYP2C11, CYP2D1, CYP3A2, UGT1A1, UGT1A3, UGT1A6, and UGT1A9 decreased. These changes may be caused by the alteration of FXR, HNF4α, LXRα, LXRβ, PXR, and RXR. In conclusion, NAFLD changes the expression and activity of hepatic drug-metabolizing enzymes and transporters in rats, which may affect drug metabolism and pharmacokinetics. In clinical medication, drug monitoring should be strengthened to avoid potential risks.
研究领域:
药理学
·
肝病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）