Frontiers in Molecular Biosciences
·
2023
·
IF 5
Zhuo Wei,Chen Juan,Jiang Shilong,Zheng Juyan,Huang Hanxue,Xie Pan,Li Wei,Lei Mengrong,Yin Jiye,Gao Ying,Liu Zhaoqian
Eukaryotic translation initiation factor 3 subunit A (eIF3a) is the largest subunit of the eukaryotic translation initiation factor 3 (eIF3). eIF3a plays an integral role in protein biosynthesis, hence impacting the onset, development, and treatment of tumors. The proteins regulated by eIF3a are still being explored in vivo. In this study, a Cre-loxP system was used to generate eIF3a conditional knockout mice. Tandem mass tag (TMT) labeling with LC-MS/MS analysis was used to identify differentially expressed proteins (DEPs) in fat, lungs, skin, and spleen tissue of the eIF3a knockout mice and controls. Bioinformatics analysis was then used to explore the functions and molecular signaling pathways of these protein landscapes. It was observed that eIF3a is essential for life sustenance. Abnormal tissue pathology was found in the lungs, fat, skin, spleen, and thymus. In total, 588, 210, 324, and 944 DEPs were quantified in the lungs, fat, skin, and spleen, respectively, of the eIF3a knockout mice as compared to the control. The quantified differentially expressed proteins were tissue-specific, except for eight proteins shared by the four tissues. A broad range of functions for eIF3a, including cellular signaling pathway, immune response, metabolism, defense response, phagocytes, and DNA replication, has been revealed using bioinformatics analysis. Herein, several pathways related to oxidative stress in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, including nitrogen metabolism, peroxisome, cytochrome P450 drug metabolism, pyruvate metabolism, PPAR signaling pathway, phospholipase D signaling pathway, B-cell receptor signaling pathway, ferroptosis, and focal adhesion, have been identified. Collectively, this study shows that eIF3a is an essential gene for sustaining life, and its downstream proteins are involved in diverse novel functions beyond mRNA translational regulation.
研究领域:
分子生物学
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蛋白质组学
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遗传学
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生物信息学
·
病理学
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产品关联
DOI
PubMed
高影响因子
XENOBIOTICA
·
2024
·
IF 1.3
Li Shao,Jiajia Mo,Qinlong Xu,Guangwei He,Chunyu Xing,Zhaoxing Chu
HY-072808 is a novel phosphodiesterase 4 inhibitor clinically used for topical atopic dermatitis treatment. Cytochrome P450 enzymes are involved in transforming it into major metabolite ZZ-24. An efficient UPLC–MS/MS method was established to detect HY-072808 and ZZ-24 in plasma and skin tissues of minipigs.One-step protein precipitation was performed with acetonitrile. Subsequently, elution was served with a methanol and water gradient containing 0.1% formic acid for 3.5 min. The plasma and skin tissue concentrations of HY-072808 and ZZ-24 showed good linearity from 0.200 to 200 ng/mL.The experimental minipigs exhibited low systemic exposure and bioavailability of 3.1–7.6% after transdermal application of 1–4% HY-072808 ointment. Multiple topical administrations over seven consecutive days showed a minor accumulation in systemic exposure, with accumulation factors of 2.3 and 4.0 for HY-072808 and ZZ-24, respectively.The distribution of HY-072808 ointment among different cortical layers in minipigs was studied for the first time. Following transdermal application of 2% HY-072808 ointment, the concentration in plasma and skin tissues in the order of epidermis > dermis > subcutaneous tissue ≈ subcutaneous muscle ≈ plasma; at 48 h after the administration, the epidermis and dermis still had a high concentration of the drug.
研究领域:
药理学
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皮肤病学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2016
·Vol. 30
·期 11
·1796-1806
·
IF 1.729
Junjun Ni,Li Xu,Wei Li,Lijun Wu
Easy-to-use early cancer detection methods based on metabolomics using serum samples have been developed recently. Among metabolites, amino acids and acylcarnitine are two of the most suitable candidates for diagnosing lung cancer. The purpose of the present study was to develop a novel, sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS) method to simultaneously determine 13 amino acids and 8 acylcarnitines in lung cancer patients in serum. After derivatization, the 21 analytes were separated using a C 18 column with gradient elution program in 14 min, obtaining recovery within 90.4–113.8% and precision within 0.3–14.8%. The method was successfully applied in concentration determination of lung cancer patients and healthy controls. The results showed that the serum concentration of lung cancer patients were significant from those of healthy controls.
研究领域:
医学
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分析化学
·
肿瘤学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2021
·
IF 3.205
Xiangling Feng,Yufeng Ding,Peng Zhang,Qiang Fu,Li Zhang,Heng Zheng
Dacomitinib, an irreversible pan-ErbB tyrosine kinase inhibitor targeting the human epidermal growth factor receptor, is used for the treatment of metastatic non-small cell lung cancer. To facilitate the investigations on its metabolism and other relevant studies, based on high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS), a rapid and sensitive bioanalytical technique was established and fully validated for simultaneous quantification of dacomitinib and its main metabolite in human plasma. The plasma samples were treated with acetonitrile containing 0.1% formic acid and the liquid supernatant was collected, dried and dissolved in methanol-water-formic acid (200:800:1, v/v) before injection. The chromatographic separation was performed on an ACE Excel C 18 column (2.1 mm × 50.0 mm, i.d., 5 μm) by gradient elution with a mixture of buffer (5 mM ammonium acetate in 0.1% formic acid) and acetonitrile, serving as the mobile phase, with an overall run time of 4 min. Dacomitinib, O-desmethyl dacomitinib and IS were subsequently detected on an AB QTRAP 5500 mass spectrometer in positive ion and multiple reaction monitoring modes at the precursor-to-product transitions of m / z 470.4 → 385.0, m / z 456.0 → 370.9 and m / z 480.2 → 385.1, respectively. The accuracy and precision of determinations were guaranteed within the concentration ranges of 0.25–100 ng/mL for dacomitinib and 0.20–80 ng/mL for O-desmethyl dacomitinib. The intra- and inter-assay accuracy ranged from 92.00% to 104.50% and the intra- and inter-assay precision was less than 8.20% for each analyte. The method was validated and the relevant parameters, including selectivity, interference among analytes and internal standard, carry-over effect, dilution integrity, extraction recovery, matrix effect, and stability, all satisfied the requirements formulated by the US Food and Drug Administration and the European Medicines Agency. The clinical applicability of the fully-validated method was evaluated in medicated samples from patients on dacomitinib.
研究领域:
药理学
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临床化学
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分析化学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2024
·Vol. 38
·期 12
·e6034
·
IF 1.8
Feng Chen,Huanhuan Li,Xiaoxia Yang,Ziwei Deng,Hongqiang Wang,Zhihua Shi,Chengfeng Qiu
To facilitate clinical therapeutic drug monitoring (TDM) of polymyxin B (PB) and polymyxin E (PE), we developed and validated a simple LC–MS/MS method for simultaneous determination of PB (including polymyxin B1 (PB1), polymyxin B2 (PB2), polymyxin B3 (PB3) and isoleucine-polymyxin B1 (ile-PB1)) and PE (including polymyxin E1 (PE1) and polymyxin E2 (PE2)) in human plasma. PB or PE was extracted from 20.0 μL plasma using a 5% (v/v) formic acid acetonitrile solution and separated on a BEH-C18 column (2.1 × 100 mm, 1.7 μm) with a mobile phase consisting of 0.8% formic acid aqueous solution and 0.2% formic acid acetonitrile solution. Gradient elution was performed over 5.5 min at a flow rate of 0.250 mL/min. Quantitative analysis was conducted in positive ion scanning mode by electrospray ionization and multiple reaction monitoring. The method validation was conducted based on bioanalytical method validation guidance, including specificity, calibration curve, precision, accuracy, recovery, matrix effect, stability and dilution integrity and all of the results satisfied the requirements. The method was simple, robust and high-throughput and is currently being used to provide a TDM service to enhancing therapeutic efficacy and safety use of the PB and PE.
研究领域:
分析化学
·
临床医学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Zi-Ling Li,Da-Jin Yang,Jia-Qi Zhao,Wen-Jie Sun,Jie Gao,Shu-Feng Song,Hou-Jun Xu,Hai-Jie Li,Fa-Ming Tian,Man-Man Wang
A novel magnetic nanoporous carbon (Fc-Fe/Ni@MPC) was fabricated from ferrocene contained metal-organic framework (MOF) and employed as multifunctional QuEChERS adsorbent for determination of triazine herbicides in various fruit and vegetable samples before LC-MS/MS. The prepared Fc-Fe/Ni@MPC not only maintained the original ordered morphology from MOF precursor, but also exhibited high graphitization and good superparamagnetism through pyrolysis. This sorbent afforded adsorption capacity of 1163.25 mg/g, 157.83 mg/g, 157.69 mg/g and 25.10 mg/g towards chlorophyll, lycopene, β -carotene and lutein via hydrophobic, π-π and hydrogen bonding interactions. The method gave negligible matrix effects of −14.2 % ∼ 10.8 %, low detection limits of 0.001–0.04 μg/kg and satisfactory recoveries of 80.2 %–112 % in orange, citrus, apple, watermelon, tomato, carrot and lettuce samples, when performing 2 mg of this single sorbent within just 15 s. This work revealed the prospect of Fc-Fe/Ni@MPC as versatile and efficient QuEChERS adsorbent for pretreatment of triazine herbicides in large kinds of pigment-rich food samples.
研究领域:
分析化学
·
食品科学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2014
·Vol. 6
·期 9
·2998-3008
·
IF 1.938
Guanghui Liu,Wei He,Hao Cai,Xiuman Sun,Waner Hou,Manna Lin,Zhiyong Xie,Qiongfeng Liao
A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously determine berberine, palmatine, coptisine, epiberberine and jatrorrhizine in rat plasma, using tetrahydropalmatine as an internal standard. The separation of the five compounds was carried out on a C18 column using a mobile phase consisting of acetonitrile and water (containing 5 mmol ammonium acetate adjusted to pH 5.0 with formic acid). The detection was performed in the multiple reaction monitoring (MRM) mode via the electrospray ionization (ESI) source operating in the positive ionization mode. Linear calibration curves were obtained over the concentration range of 0.20–200.0 ng ml−1 for berberine, and 0.20–100.0 ng ml−1 for palmatine, coptisine, epiberberine and jatrorrhizine. The accuracy, precision and extraction recovery of the five analytes were all satisfactory. The validated method was successfully applied to study the pharmacokinetic differences of the five protoberberine-type alkaloids after the oral administration of Rhizoma coptidis (RC) and Jiao-Tai-Wan (JTW) extract. It was found that the Tmax values of the five ingredients in the JTW extract were significantly increased (P < 0.05) when compared with those in RC. In addition, the AUC0–t of palmatine, coptisine and epiberberine were significantly increased (P < 0.05).
研究领域:
药理学
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分析化学
·
中医药学
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2018
·
IF 6.735
Lin Liu,Sen Lin,Wei Zhang,Usman Farooq,Genxiang Shen,Shuangqing Hu
Sulfachloropyridazine (SCP) has significant threat to natural environment and human health worldwide. Efforts have been made to remove SCP using traditional water treatment technologies but the outputs achieved are limited. In this study, we focused on heat-activated persulfate oxidation of SCP. Various factors have been investigated, such as PS concentration, initial pH, temperature and natural water constituent effects. The results showed that the SCP removal rate constants (k obs ) followed a quadratic relationship with initial persulfate concentrations (k obs = −1.526 ∗ 10 −6 [PS] 0 2 + 5.621 ∗ 10 −4 [PS] 0 + 0.01158, R 2 = 0.923, [PS] 0 = 17.5–280 µM) and excellent fitting with the Arrhenius equation (ln (k obs ) = −19487.9/T + 59.63, R 2 = 0.967, T = 303.15–323.15 K). The pH tests were applied at a wide range of 3.0–10.0, the quickest degradation rate observed at pH 3.0. The consumption rate of PS was strengthened at elevated temperatures, and 40 °C was determined to be an optimal condition. The presence of chloride (Cl − ), bicarbonate (HCO 3 − ) and humic acid all showed inhibitory effects. The radical scavenging experiments revealed that HO and SO 4 − were predominant oxidizing species responsible for SCP removal. These oxidizing species were further verified by EPR tests. LC-MS/MS analysis confirmed seven kinds of byproducts during the removal process which are mainly deriving from SO 2 extrusion/Smile-type rearrangement and S-N bond cleavage. Efficiencies of the antibiotics removal were over 85% when 50 g L −1 PS was added to piggery anaerobic fermentation slurry. This remediation technology may appear as a promising way for the removal of highly antibiotics-contaminated water in a small scale.
研究领域:
环境科学
·
水处理
·
化学工程
·
分析化学
✓ 已验证
DOI
高影响因子
CHEMOSPHERE
·
2021
·
IF 7.086
Jingyi Fu,Li Feng,Yongze Liu,Liqiu Zhang,Shuo Li
Electrochemical activation of peroxymonosulfate (PMS) at carbon cloth anode (E (Carbon cloth Anode)/PMS system) was investigated for sulfamethoxazole (SMX) degradation. The results indicated that PMS could be activated at carbon cloth anode during electrolysis, resulting in the improvement of SMX degradation. The degradation efficiency of SMX was facilitated with the higher PMS concentration and current density, respectively. The degradation rate constant of SMX increased with the rising pH from 3.6 to 6.0, and reached the highest value at pH 6.0, and then decreased with further increasing pH to 8.0. The presence of chloride ion (Cl − , 5–100 mM) significantly enhanced SMX degradation, while addition of humic acid (HA, 1–5 mgC L −1 ) inhibited SMX degradation. Addition of carbonate (HCO 3 − , 5–20 mM) had a negligible impact on SMX degradation. Small amounts of phosphate (PO 4 3− , 0–5 mM) could promote degradation, while a large amount of PO 4 3− (10–20 mM) inhibited the degradation. Moreover, the quenching experiments demonstrated that sulfate radical (SO 4 · − ), hydroxyl radical (·OH) and singlet oxygen ( 1 O 2 ) contributed to SMX degradation in E (Carbon cloth Anode)/PMS system. The degradation intermediates of SMX were identified by LC-MS/MS and the degradation pathways were deduced to be hydroxylation, the cleavage of S–N bond, and oxidation of aniline group. Moreover, the micronucleus test of Vicia faba root tips indicated that the E (Carbon Cloth Anode)/PMS system could reduce the genetic toxicity of SMX contaminated water to some extent.
研究领域:
环境化学
·
电化学
·
水处理
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Marine Drugs
·
2026
·Vol. 24
·期 6
·215
·
IF 5.7
Xiaochen Niu,Jun Zhao,Deqi Ding,Wei He,Guanhua Du,Jiejie Hao,Jianchun Zhao
LY104 (previously designated as B7) is a selective phosphodiesterase 4 inhibitor with promising activity against chronic obstructive pulmonary disease. We previously reported its single-dose pharmacokinetics and tissue distribution in rats. In the present study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of LY104 and its major metabolite M1 in rat plasma following ICH M10 guidelines. The method showed excellent linearity over 20–1200 ng/mL for both analytes, with retention times of 2.85 min (LY104) and 3.22 min (M1). Using this method, we extended our previous work in several directions. Re-analysis of previously published single-dose pharmacokinetic and tissue distribution data revealed no significant sex differences for LY104. Newly generated multiple-dose studies (1 mg/kg daily for 7 days) demonstrated no accumulation of LY104 or M1. The pharmacokinetic profile of M1 was quantified for the first time. Comprehensive in vitro investigations included plasma and liver microsomal stability, plasma protein binding, and excretion studies. This systematic preclinical pharmacokinetic characterization of LY104 and M1, incorporating re-analysis of existing data with sex stratification, newly generated multiple-dose and metabolite data, excretion studies, and comprehensive in vitro investigations, provides useful information to support further drug development and clinical trial design.
✓ 已验证
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2021
·
IF 7.514
Yufei Yang,Shudong He,Yi Zhang,Xingjiang Li,Haiyan Liu,Qiming Li,Xiaodong Cao,Yongkang Ye,Hanju Sun
Ethanol protocol, two-step protocol and enzymatic extraction were used to extract prolamins from seven kidney beans ( P. vulgaris L.) compared with Osborne protocol. 70–80% (v/v) ethanol concentrations were beneficial to the extraction, and two-step protocol was conducive to higher prolamin content. Varied protein subunits were observed in electrophoresis profiles, and further differences in composition were identified by LC-MS/MS while potential functions were annotated. Stronger hydrophobicity was found with prolamins enrichment from light speckled kidney bean (LSKB), black speckled kidney bean (BSKB), and red kidney bean (RKB), which was negative correlation with α-helix content based on the principal component analysis (PCA). The crude prolamins from the two kinds of white kidney beans possessed higher sulfhydryl and exhibited better water holding capacity (WHC), while higher oil absorption capacity (OAC) was observed in LSKB, BSKB, and RKB. Compared with zein, kidney bean prolamins could be used as food packaging materials due to hydrophobicity.
研究领域:
食品科学
·
植物科学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 69
·43621-43635
·
IF 3.108
Huanyu Guan,Xiaoming Wang,Shiping Wang,Yang He,Jiajing Yue,Shanggao Liao,Yuanda Huang,Yue Shi
Shengjiang Xiexin decoction (SXD) exerts protective effects against gastrointestinal injury induced by irinotecan hydrochloride (CPT-11). The intestinal bacteria-associated in vitro pharmacokinetics of 16 components of SXD in normal rats and those with CPT-11-induced gastrointestinal toxicity were compared in this study. A sensitive and reproducible ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) method was developed for the quantification of 16 components of SXD in a rat intestinal bacteria incubation system, using naringin, naringenin and tetrahydropalmatine as internal standards (ISs). The samples were prepared via salting-out assisted liquid–liquid extraction (SALLE) with NaCl to reduce matrix effects. Chromatographic separation was performed on a sub-2 μm analytical column with acetonitrile and 0.1% aqueous formic acid as mobile phase. All of the analyzed components and ISs were detected via multiple reaction monitoring (MRM) scanning with electrospray ionization. The proposed method was successfully applied for the in vitro pharmacokinetic analysis of the multiple components of a complex mixture consisting of a traditional Chinese medicine (TCM) and an intestinal bacterial incubation system. The pharmacokinetic parameters of some flavonoid glycosides and aglycones in the rats with CPT-11-induced gastrointestinal toxicity were significantly different (p < 0.05, p < 0.01) from those in the normal rats, which suggested that consumption of CPT-11 could qualitatively and/or quantitatively alter the intestinal bacteria as well as the metabolic activities of enzymes. The in vitro pharmacokinetic analysis of these components in the intestinal bacterial incubation system provided valuable information for achieving a deeper understanding of the mechanisms involved in the alteration of intestinal bacteria induced by CPT-11 and further in vivo pharmacokinetic research on SXD. The intestinal bacteria-based pharmacokinetic method could benefit the study of interactions between TCMs and chemical drugs in clinical use.
研究领域:
药理学
·
中药学
·
胃肠病学
·
分析化学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）