MICROCHEMICAL JOURNAL
·
2021
·
IF 4.821
Zhongying Zhang,Ranxi Ni,Piao Chen,Xiaolan Zhu,Zilong Zhang,Jingdong Peng
In the present study, a convenient, selective and sensitive method of high performance liquid chromatography combined with resonance Rayleigh scattering (HPLC-RRS) for the detection of proton pump inhibitors (PPIs) was proposed based on enhancing the volume and hydrophobicity of PPIs by introducing Eosin Y (EY) and Pd(II). In order to investigate the interaction and the mechanism of signal enhancement, the complexes were characterized by ultraviolet–visible spectrum (UV), dynamic light scattering (DLS), RRS, scanning electron microscope (SEM) and the calculation of the density functional theory (DFT). The results indicated that PPIs, Pd(II) and EY formed ionic associations at 1:1:2 due to electrostatic attraction, which increased the volume and hydrophobicity of the system, resulting in the enhancement of RRS signals. Under the optimized experimental conditions, a linear relationship was found between RRS intensity and the concentration of PPIs within 0.02–25.00 μg mL −1 . The limits of detection were 10.1, 5.6, 7.5 and 8.3 ng mL −1 for rabeprazole, omeprazole, pantoprazole, and lansoprazole, respectively. In addition, the established simple, reliable and cheap method was validated and applied for the human serum samples, which indicated broad application prospects in drugs.
研究领域:
分析化学
·
药物分析
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产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2018
·
IF 3.457
Miao Yan,Zhu-feng Wu,Dan Tang,Feng Wang,Yi-wen Xiao,Ping Xu,Bi-kui Zhang,Yi-ping Liu,Da-xiong Xiang,Hoan Linh Banh
Voriconazole (VRC) and proton pump inhibitors (PPIs) have similar metabolic pathways. The objectives of the study are to evaluate the impact of PPIs on the pharmacokinetics of VRC. Human liver microsomes model was applied to assess the inhibitory effects of PPIs on the metabolism of VRC in vitro. A retrospective study was also carried out to explore the relationship between the plasma VRC trough concentrations and PPIs uses. Patients were divided into six groups: control (n = 166), lansoprazole (LAN, n = 38), esomeprazole (ESO, n = 19), omeprazole (OME, n = 45), pantoprazole (PAN, n = 43), and ilaprazole (ILA, n = 38) groups. All five PPIs showed concentration-dependent inhibitory effects on the VRC metabolism in human liver microsomes, among which LAN, OME and ESO were three of the most potent inhibitors. Consistently, co-administered with LAN, OME and ESO significantly increased the plasma VRC trough levels ( p < 0.05), whereas there was no significant association between VRC concentrations and PAN or ILA use. Interestingly, patients in the PPIs groups were more likely to reach the therapeutic VRC range of 1–5.5 μg/mL in steady state when compared with control patients (75–81% VS 69%). In conclusion, although all PPIs showed inhibitory effects on the VRC metabolism in vitro, only LAN, OME and ESO significantly increased VRC plasma concentrations. This study should be helpful for choice of the type of PPIs for patients administered with VRC.
研究领域:
临床药理学
·
药物代谢
·
医学研究
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产品关联
DOI
PubMed
高影响因子
Pharmacogenomics & Personalized Medicine
·
2021
·
IF 3.912
Magesa Mafuru,Sanlan Wu,Henry Mayala,Zaituni Msengwa,Amani Phillip,Charles Mgone
Purpose To analyze the combined effect of CYP2C19 genetic polymorphism and PPIs coadministration on voriconazole trough concentration (VCZ-Ctrough) in Chinese patients with hematological disorders.Patients and Methods A prospective observational study involved 250 plasma samples from 114 adult patients receiving voriconazole with or without PPIs were analyzed. Demographics and clinical characteristics were obtained from patient’s records. A validated LC-MS/MS was used to quantify the plasma VCZ-Ctrough. Genotyping for CYP2C19*2 and CYP2C19*3 variant alleles was performed by PCR-RFLP followed by DNA sequencing. The combined total score (from 2 to 5) was calculated for each patient. The higher the score, the lesser the metabolism of the patient.Findings Fifty percent of patients administered with voriconazole were coadministered with PPIs, predominantly omeprazole or esomeprazole. Patients exhibiting CYP2C19 poor metabolizer phenotype showed a significantly higher median VCZ-Ctrough, (4.31µg/mL [IQR, 1.64µg/mL–7.36µg/mL]) than patients with normal metabolizer (1.38µg/mL, [IQR, 0.79µg/mL–2.14µg/mL], p < 0.0001). Similarly, patients co-administration with PPIs had higher median VCZ-Ctrough (2.86µg/mL [IQR 1.33µg/mL–4.66µg/mL]), than PPIs non-users (1.71µg/mL, [IQR, 0.86µg/mL–3.48µg/mL], p = 0.001). However, we noted that the median VCZ-Ctrough for each factor was ranging within the normal recommended therapeutic range in the Chinese population (0.5µg/mL–5µg/mL). But when the two factors were combined, the median VCZ-Ctrough was steadily increasing as the metabolic capacity (reflected by combined total score) was increasing. Importantly, the median VCZ-Ctrough in PM/PPIs user (total score 5) was significantly elevated to supra-therapeutic levels compared to NM/PPI non-user group (total score 2) (5.83µg/mL [IQR, 2.19µg/mL–9.51µg/mL] versus 1.13µg/mL [IQR, 0.67µg/mL–1.82µg/mL]), respectively, P < 0.0001. Furthermore, we observed that the elevation of median VCZ-Ctrough to supra-therapeutic levels was largely contributed by omeprazole or esomeprazole compared to lansoprazole or pantoprazole.Conclusion Coadministration with PPIs significantly increased voriconazole trough concentrations and there was an additive effect in CYP2C19 PMs, who were most likely to have supra-therapeutic levels.
研究领域:
药理学
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临床医学
·
遗传学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2022
·
IF 18.027
Dandan Wang,Yong Wang,Haijuan Li,Yanchao Han,Ping Hu,Kongshuo Ma,Mordechai Sheves,Yongdong Jin
Nanofluidics is an emerging hot field that explores the unusual behaviors of ions/molecules transporting through nanoscale channels, which possesses a broad application prospect. However, in situ probing bioactivity of functional proteins on a single-molecule level by a nanofluidic device has not been reported, and it is still a big challenge in the field. Herein, we reported a biological nanofluidic device with a single-protein sensitivity, based on natural proton-pumping protein, bacteriorhodopsin (bR), and a single SiNx nanopore. Nanofluidic single-molecule probing of bR proton-pumping activity and its light response were achieved under applied voltage of 0 V, by biologically self-powered steady-state ionic current nanopore sensing. Green-light irradiation of the device led to the monitoring of a steady-state proton current of ∼3.51 pA/per bR trimer, corresponding to charge density of 815 μC/cm2 generated by each bR monomer, which far exceeded the previously reported value of 1.4 μC/cm2. This finding and method would promote the development of artificial biological and hybrid nanofluidic devices in biosensing and energy conversion applications.
研究领域:
纳米流体学
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生物物理学
·
生物传感
·
能量转换
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DOI
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2023
·Vol. 396
·期 8
·1759-1771
·
IF 3.6
Liu Fei,Xu Yanjun,Wang Li,Ma Xifeng,Zhang Zhen,Zhuang Xiaomei
Anaprazole, a new proton pump inhibitor (PPI), is designed for the treatment of acid-related diseases, such as gastric ulcers and gastroesophageal reflux. This study explored the in vitro metabolic transformation of anaprazole. The metabolic stabilities of anaprazole in human plasma and human liver microsomes (HLM) were analyzed by liquid chromatography-tandem mass spectrometry (LC–MS/MS). Then, the contribution (%) of non-enzymatic and cytochrome P450s (CYPs) enzyme-mediated anaprazole metabolism was assessed. To obtain the metabolic pathways of anaprazole, the metabolites generated in HLM, thermal deactivated HLM, and cDNA-expressed recombinant CYPs incubation systems were identified by ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF–MS). Results showed that anaprazole was very stable in human plasma and unstable in HLM. The contribution (%) of non-enzymatic vs . CYPs enzyme-mediated metabolism was 49% vs . 51%. CYP3A4 was the major enzyme (48.3%), followed by CYP2C9 (17.7%) and CYP2C8 (12.3%), in responsible for the metabolism of anaprazole. Specific chemical inhibitors targeting CYP enzymes notably blocked the metabolic transformation of anaprazole. Six metabolites of anaprazole were identified in the non-enzymatic system, whereas 17 metabolites were generated in HLM. The biotransformation reactions mainly included sulfoxide reduction to thioether, sulfoxide oxidation to sulfone, deoxidation, dehydrogenation, O-dealkylation or O-demethylation of thioether, O-demethylation and dehydrogenation of thioether, O-dealkylation and dehydrogenation of thioether, thioether O-dealkylation and dehydrogenation of thioether, and O-dealkylation of sulfone. Both enzymatic and non-enzymatic metabolisms contribute to the clearance of anaprazole in human. Anaprazole is less likely to develop drug-drug interactions in clinical use compared to other PPIs.
研究领域:
药理学
·
药物代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Gut Pathogens
·
2022
·Vol. 14
·期 1
·1-11
·
IF 5.324
Brusselaers Nele,Pereira Marcela,Alm Johan,Engstrand Lars,Engstrand Lilja Helene
Background The effects of proton-pump inhibitors (PPIs) on the infant microbiome remain unclear. Swedish pilot cohort study to assess the longitudinal effect of long-term PPI on the infant gut microbiome, including ten newborn infants operated for esophageal atresia exposed to PPIs (mean 57 weeks), compared to healthy one-year-old controls. All children were born vaginally and were otherwise healthy. Within- and between sample diversity of the fecal microbiome was assessed using untargeted whole genome Shotgun metagenomics which sequences all the DNA in the sample and can capture genes rather than a taxonomic fingerprint.Results A longer duration of PPI-use was associated with considerable changes in evenness and high variation on diversity within samples compared to a shorter duration of use. The limited difference between baseline samples and controls suggests that this shift was most likely due to the drug exposure and not the underlying alterations on the microbiome. We found no associations with the number of antibiotic treatment episodes among the PPI-users.Conclusion Prolonged PPI-use may alter the early infant gut microbiome composition, especially those with the most prolonged duration of use.
研究领域:
医学
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微生物学
·
儿科学
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DOI
PubMed
高影响因子
ANALYST
·
2017
·Vol. 142
·期 5
·745-751
·
IF 3.885
Lu Wang,Yunfeng Chai,Wenquan Zhu,Yuanjiang Pan,Cuirong Sun,Su Zeng
Mutual chiral recognition of four stereoisomers of tadalafil and three pairs of enantiomers of proton pump inhibitors (PPIs) including pantoprazole, lansoprazole, and omeprazole, as well as quantitative analysis of enantiomeric excess is achieved on the basis of the competitive fragmentation of doubly charged trimeric NiII cluster ions. Compared with a singly charged trimeric cluster ion, a doubly charged trimeric cluster ion was proved efficient in the recognition of chiral drugs with one or multiple chiral centers, due to its rich fragmentation ions. Upon collision-induced dissociation (CID), the cluster ion [NiII(PPIs)(tadalafil)2]2+ yielded two diagnostic ions [tadalafil + H]+ and [tadalafil − benzo[d][1,3]dixoloe]+ through electrospray ionization quadrupole time-of-flight mass spectrometry. The abundance ratio of the two fragment ions relied mainly on the configuration of PPIs and tadalafil, and therefore the chiral selectivity (Rchiral) of one enantiomer relative to the others is different. The chiral recognition of all four stereoisomers of tadalafil was achieved by using S configuration PPIs as references, and S-omeprazole showed the best selectivity. The Rchiral values for R,R/S,S, R,S/S,R, R,R/R,S and R,R/S,R-tadalafils were 1.47, 1.17, 2.37, and 2.10, respectively. In a reciprocal process, the Rchiral was 1.36 and 1.31 for R/S-pantoprazole and R/S-lansoprazole, respectively, by using R,R-tadalafil as a reference. Although omeprazole is a racemic drug, it can also be discriminated with S-omeprazole. Calibration curves were constructed with favorable correlation coefficients (r2 > 0.991) by relating the ln(Rchiral) values to the isomeric composition in a mixture. The sensitivity of the methodology allows mixtures to be analyzed for the enantiomeric excess (ee) by recording the ratios of fragment ion abundances in a mass spectrum. The sensitivity of the methodology allowed the determination of enantiomeric impurities of 5% molar composition in individual compounds present in mixtures; the diastereoisomeric impurity of R,R-tadalafil could be quantified even at 1%. We believe that the developed method not only has scientific significance in qualitative and quantitative chiral analyses of tadalafil and PPIs, but also provides great opportunity for enabling the discrimination on a wide range of chiral drugs.
研究领域:
分析化学
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药物化学
·
质谱分析
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Mengyao Mu,Mengmeng Zhang,Jie Liu,Ke Ren,Hui Liu,Lixian Yip,Kai Guo,Feifei Teng,Jian Dong,Xueli Xu,David Tai Leong,Xiao Sun
Traditional antitumor strategies often require sufficient time to assess the effectiveness according to changes in tumor structure. Once ineffective, patients may miss the critical window for pursuing alternative treatment options. Herein, a manganese sulfide nanoplatform loaded with proton pump inhibitor (PPI) is developed. This nanoplatform is designed for visualizing tumor acidosis degree by magnetic resonance imaging (MRI), achieving real-time therapeutic efficacy precognition. The nanoplatform releases PPI, H 2 S, and Mn 2+ within the acidic lysosome of tumor cells. PPI inhibits V-ATPase expression, leading to an increase in intracellular H + levels. H 2 S accelerates glucose consumption of tumor cells, producing more lactic acid and further inducing tumor acidosis. Tumor acidosis in turn accelerates the nanoplatform's degradation, achieving higher tumor MRI. As the tumor acidosis degree correlates positively with tumor regression, real-time visualization of acidosis degree effectively predicts future therapeutics. Interestingly, tumor acidosis achieves efficient tumor metastasis suppression rather than increases it. Overall, this work presents a nanoplatform capable of visualizing tumor acidosis in real-time and precisely predicting future therapeutics.
研究领域:
肿瘤学
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医学影像学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
MICROBIAL PATHOGENESIS
·
2019
·
IF 2.581
Xiaonan Chen,Pengyu Li,Yuanna Shen,Yiqing Zou,Gang Yuan,Haiyan Hu
Antibiotics resistance of H. pylori has been increasing constantly accompanied with decreasing clearance rate clinically, which is demonstrated to be closely related to biofilms with higher resistance than planktonic bacteria for the dense extracellular polymeric substances . Rhamnolipid (RHL) is proved to not only damage the structure of biofilm, but also potentially inhibit bacterial adhesion . To investigate if RHL could promote eradicating rate of the conventional triple therapy to H. pylori biofilm and hence attenuate the resistance and relapse of H. pylori , first-line antibiotics clarithromycin (CLR), amoxicillin (AMX) or/and proton pump inhibitor (PPI) involved single, dual or triple therapies were compared with RHL-containing drug combinations on eradicating H. pylori biofilm. The residual biofilm biomass, the survival of bacteria inside the remaining biofilm and the planktonic bacteria dispersed from the biofilm after treatment were tested. Combination with RHL significantly improved the ability of antibiotics to eradicate H. pylori biofilm, especially RHL combined with AMX and PPI could eradicate more than 95% of biofilm showing much more effective ability than the conventional triple therapy CLR + AMX + PPI. Additionally, the combination of RHL and antibiotics could effectively inhibit the biofilm formation at lower concentration. Thus, RHL might be used as a potential antibiotic adjuvant on anti- H. pylori therapy to enhance eradicating ability of antibiotics to biofilms.
研究领域:
微生物学
·
药理学
·
传染病学
✓ 已验证
DOI
PubMed
高影响因子
TREE PHYSIOLOGY
·
2024
·
IF 3.5
Liu Jian,Li Jing,Deng Chen,Liu Zhe,Yin Kexin,Zhang Ying,Zhao Ziyan,Zhao Rui,Zhao Nan,Zhou Xiaoyang,Chen Shaoliang
Nitrogen (N) plays an important role in mitigating salt stress in tree species. We investigate the genotypic differences in the uptake of ammonium (NH4+) and nitrate (NO3−) and the importance for salt tolerance in two contrasting poplars, salt-tolerant Populus euphratica and salt-sensitive P. popularis. Total N content, growth, and photosynthesis were significantly reduced in P. popularis after 7 days exposure to NaCl (100 mM) supplied with 1 mM NH4+ and 1 mM NO3−, while the salt effects were not pronounced in P. euphratica. The 15NH4+ trace and root flux profiles showed that salt-stressed poplars retained ammonium uptake, which was related to the up-regulation of ammonium transporters (AMTs) in roots, as two of the four AMTs tested significantly increased in salt-stressed P. euphratica (i.e., AMT1.2, 2.1) and P. popularis (i.e., AMT1.1, 1.6). It should be noted that P. euphratica differs from salt-sensitive poplar in the maintenance of NO3− under salinity. 15NO3− tracing and root flux profiles showed that P. euphratica maintained nitrate uptake and transport, while the capacity to uptake NO3− was limited in salt-sensitive P. popularis. Salt increased the transcription of nitrate transporters (NRTs), NRT1.1, 1.2, 2.4, 3.1, in P. euphratica, while P. popularis showed a decrease in the transcripts of NRT1.1, 2.4, 3.1 after 7 days of salt stress. Furthermore, salt-stimulated transcription of plasmalemma H+-ATPases (HAs), HA2, HA4 and HA11 contributed to H+-pump activation and NO3− uptake in P. euphratica. However, salt stimulation of HAs was less pronounced in P. popularis, where a decrease in HA2 transcripts was observed in the stressed roots. We conclude that the salinity-decreased transcripts of NRTs and HAs reduced the ability to uptake NO3− in P. popularis, resulting in limited nitrogen supply. In comparison, P. euphratica maintains NH4+ and NO3− supply, mitigating the negative effects of salt stress.
研究领域:
植物学
·
植物生理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2017
·
IF 2.896
Cheng-yuan Li,Mei Su,Yun-yi Yan,Lin Zhou,Lu-yao Ao,Wei-rong Fang,Yun-man Li
1-(5-(1H-indol-5-yl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine (KFP-H008)，a novel and potent potassium-competitive acid blocker for the treatment of acid secretion related diseases, has not been reported previously. In this study, we demonstrated that KFP-H008 inhibits basal acid secretion, 2-deoxy- D -glucose- (2DG-) stimulated gastric acid secretion in rats. KFP-H008 blocked histamine-stimulated acid secretion in rats and heidenhain pouch dogs and reversed acid output in isolated gastric perfusion under histamine stimulation. In all the animal experiments, KFP-H008 exerted a more effective, potent and longer-lasting inhibitory action in comparison with lansoprazole , a proton pump inhibitor (PPI) commonly used in clinic. KFP-H008 inhibited H + -K + -ATPase activity both at pH 6.5 and pH 7.5, and was unaffected by pH. The inhibitory action was reversible and was achieved in a K + -competitive manner. Furthermore, KFP-H008 did not affect Na + -K + -ATPase activity, thus exhibiting high selectivity, which is different from PPIs. In all, KFP-H008, a novel potassium-competitive acid blocker, may provide new option for the patients with acid-related diseases and provide longer-lasting inhibitory action than drugs commonly used in clinical treatment.
研究领域:
药理学
·
胃肠病学
·
药物开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2021
·Vol. 44
·期 17
·3295-3304
·
IF 3.645
Xiuyu Sui,Jin Guan,Xiaoyu Li,Lei Gu,Feng Yan,Shuang Shi,Dongxiang Zhang
An open tubular capillary electrochromatography column was prepared by immobilizing β-cyclodextrin on the inner wall of pretreated capillary via noncovalent adsorption of polydopamine. The resulting coating layer on the capillary was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. Electroosmotic flow was studied to evaluate the variation of the immobilized columns. The prepared columns showed good chiral separation performance toward five proton pump inhibitors including lansoprazole, pantoprazole, tenatoprazole, rabeprazole, and omeprazole. The influences of β-cyclodextrin concentration, coating time, buffer pH, buffer concentration, and applied voltage on separation were investigated. In the optimum conditions, the enantiomers of five analytes were fully resolved within 15 min with high resolutions of 4.57 to 8.13. The method was extensively validated in terms of accuracy, precision, and linearity and proved to be robust. The relative standard deviation values for migration times and peak areas of the analytes representing intraday and interday were less than 1.9 and 3.6%, respectively. Further, the polydopamine/β-cyclodextrin coated capillary column could be successively used over 100 runs without showing significant decrease in the separation efficiency.
研究领域:
分析化学
·
色谱学
·
药物分析
·
分离科学
✓ 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）