EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6
Yanping Li,Haoran Liu,Ronghao Fang,Jiamin Jin,Feng Yang,Jian Chen,Juzheng Zhang
Metal-based drugs have been used in the clinical treatment of tumors for over 30 years. However, no metal-based drugs have been clinically approved to treat glioma. Although metal complexes have excellent cytotoxicity, their most critical problem is crossing the blood–brain barrier. Therefore, to enable metal complexes to cross blood–brain barrier and target glioma therapy, herein, we propose to rationally used the basic structure of diazepam (5-chlorobenzophenone) and thiosemicarbazide to synthesize gold (Au) complexes C1, C2 and C3 with antiglioma activity. The C3 complex with two methyl groups attached to the N3 of thiosemicarbazone exhibited excellent cytotoxicity to glioma cells through its multiaction mechanism against glioma, inducing apoptosis, autophagy death, and deoxyribonucleic acid damage. In addition, the synthesized C3 complex can effectively cross the blood–brain barrier and accumulate in glioma, considerably decreasing the untoward reaction in vivo . Our findings provide a novel strategy for designing metal-based complexes for the treatment of glioma.
研究领域:
药理学
·
肿瘤学
·
金属药物设计
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MARINE POLLUTION BULLETIN
·
2025
·
IF 4.9
Hao-jie Zheng,Xu-feng Wang,Ye-ni Zhang,Chao-ping Hou,Ke Huang
Diazepam (DIAZ), a widely prescribed benzodiazepine for insomnia and anxiety, has been frequently detected in aquatic ecosystems, raising concerns about potential impacts on human and animal health. To investigate its environmental presence, water and sediment samples were collected from 187 aquaculture ponds across the Pearl River Delta, China. The concentrations of DIAZ and its metabolites—nordazepam (NDZ), oxazepam (OXZ), and temazepam (TEM)—were determined using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Detection frequencies in water ranged from 0.535 % to 58.8 %, with concentrations from below detection (nd) to 392 ng·L −1 , whereas in sediments, frequencies ranged from 1.07 % to 35.8 %, with levels from nd to 1.66 μg·kg −1 . Marked spatial variability was evident, with aquaculture ponds in Foshan (FS) exhibiting the highest DIAZ concentration (392 ng·L −1 ), while Zhongshan (ZS) displayed higher detection frequencies but lower concentrations. Fish ponds contained significantly greater cumulative concentrations of DIAZ and its metabolites compared with shrimp ponds. Strong positive correlations were identified between DIAZ in water and DIAZ and NDZ in sediments. Similarly, NDZ in water was strongly correlated with NDZ and DIAZ in sediments, and TEM in water showed significant correlations with DIAZ and NDZ in sediments. Environmental risk assessment revealed that NDZ and OXZ presented low ecological risks in both matrices at all sites, whereas DIAZ and TEM posed medium to high risks at certain water sites, with DIAZ also showing medium risks in some sediments. The study provides an integrated evaluation of occurrence, spatial distribution, and ecological risks of DIAZ and its metabolites in aquaculture systems, offering critical evidence to support food safety measures and strategies for pharmaceutical pollution control in the Pearl River Delta.
研究领域:
环境科学
·
药物代谢
·
生态毒理学
·
水生生态系统
·
环境污染
·
食品安全
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Yue Wang,Quanying Qu,Xiao Xiao,Tianyu Wang,Han Yan,Wei Wu,Qinzhi Wang
In this work, a high-performance lychee-like plasmonic nanocomplex with programmable hierarchical structure (Ag@ZIF-8@Au) was successfully fabricated as surface enhanced Raman scattering (SERS) platform via layer-by-layer assembly for sensitive detection of diazepam (DZP). ZIF-8 has good pre-enrichment for DZP as well as works as a skeleton for preventing aggregation of plasmonic nanoparticles, dramatically boosting sensitivity, stability and reproducibility of the SERS substrate. Furthermore, lychee-like Ag@ZIF-8@Au nanostructures provided numerous SERS “hot spots” for generating the synergistic enhancement effects including lightning rod and resonance coupling effects. By leveraging Ag@ZIF-8@Au substrate, DZP can be exquisitely detected. The detection limit plummets to 0.126 ng mL −1 , while a broad linear detection span of 10 −9 –10 −2 g mL −1 is achieved. Additionally, Ag@ZIF-8@Au can be utilized to identify DZP in aquatic products with a satisfactory recovery rate of 85.3 % to 111.9 %, which indicates its good practical applicability and great potential for monitoring safety of aquatic products.
研究领域:
材料科学
·
食品安全检测
✓ 已验证
产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2016
·
IF 4.758
Ning Xu,Jialei Bai,Yuan Peng,Zhiwei Qie,Zengshan Liu,Hongzhi Tang,Chao Liu,Zhixian Gao,Baoan Ning
Diazepam (DZP) has increasingly appeared in the nonmedical field, posing an ever-growing threat to public-health safety. Methods that accelerate and simplify the on-site detection of DZP are urgently needed. In this study, we investigated the feasibility of applying a flow-injection analysis (FIA)-based thermometric enzyme-linked immunosorbent assay (TELISA) biosensing strategy to rapidly detect DZP in real samples. The scheme involved three key steps: 1) FIA-TELISA was modified to optimize performance in DZP detection; 2) the selected samples that were spiked with a predetermined amount of DZP were respectively determined; and 3) detection results were validated by high-performance liquid chromatography. After calibrations, a linear range of 45.37–726.71 ng mL −1 was obtained, with a corresponding detection limit of 33.71 ng mL −1 . During the continuous detection, each sample required 15 min to generate an entire heat signal, and the cycle time including regeneration and retrimming was <45 min. Verification results showed that the performance characteristics of FIA-TELISA in practical applications could meet the requirements of DZP detection. Notably, pretreatment did not require elaborate extraction procedures to correct the matrix effect of the beverages. Other potential applications of TELISA technology, including the possibility of developing an in vitro assay model to analyze diverse targets, are being discussed.
研究领域:
分析化学
·
生物医学工程
·
食品安全检测
✓ 已验证
DOI
高影响因子
Foods
·
2025
·Vol. 14
·期 23
·4087
·
IF 5.1
Mengqiong Yang,Guangming Mei,Daoxiang Huang,Xiaojun Zhang,Pengfei He
A method combining magnetic solid-phase extraction (MSPE) with ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was developed for the determination of diazepam residues in aquatic products. A novel magnetic nanoparticle material, Fe3O4@SiO2@DVB-NVP, was synthesized and applied as an adsorbent for sample cleanup. The sample preparation procedure involved extraction with 1% ammonia–acetonitrile, followed by purification using the MSPE technique to efficiently remove matrix interferents. Chromatographic separation was achieved on an ACQUITY UPLC BEH C18column with a gradient elution program using a mobile phase composed of 0.1% formic acid–2 mM ammonium acetate solution and methanol. Detection was performed under multiple-reaction monitoring (MRM) mode with positive electrospray ionization (ESI+). Quantification was carried out using the external standard method. The synthesized magnetic material was characterized using SEM, TEM, FTIR, XRD, BET, and VSM, confirming its mesoporous structure, strong adsorption capacity, and excellent magnetic responsiveness. The method demonstrated good linearity over the concentration range of 0.25–50 μg/L (r2= 0.997). The limits of detection and quantification were 0.20 μg/kg and 0.50 μg/kg, respectively. Average recoveries from spiked blank matrices at three levels (0.5, 2.5, and 5.0 μg/kg) ranged from 89.3% to 119.7%, with relative standard deviations (RSDs) between 0.8% and 10.2%. The proposed method is highly selective, exhibits minimal matrix interference, and provides reliable quantitative performance, making it suitable for the qualitative and quantitative analysis of diazepam residues in aquatic products.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Foods
·
2025
·Vol. 14
·期 14
·2421
·
IF 5.1
Mengqiong Yang,Guangming Mei,Daoxiang Huang,Xiaojun Zhang,Pengfei He,Si Chen
A sensitive method was developed for detecting diazepam residues in aquatic products using magnetic dispersive solid-phase extraction (MDSPE) coupled with ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Samples extracted with 1% ammonia–acetonitrile were purified using synthesized Fe3O4@SiO2-PSA nanoparticles via MDSPE before UPLC-MS/MS analysis. Separation was performed on a C18column with gradient elution using 0.1% formic acid–2 mM ammonium acetate/methanol. Detection employed positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode. Characterization confirmed Fe3O4@SiO2-PSA’s mesoporous structure with excellent adsorption capacity and magnetic properties. The method showed good linearity (0.1–10 μg/L,r> 0.99) with an LOD and LOQ of 0.20 μg/kg and 0.50 μg/kg, respectively. Recoveries at 0.5–15.0 µg/kg spiking levels were 74.9–109% (RSDs 1.24–11.6%). This approach provides rapid, accurate, and high-precision analysis of diazepam in aquatic products, meeting regulatory requirements.
研究领域:
分析化学
·
食品安全
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Minjuan Sun,Zhijian Yuan,Menghan Li,Xuming Ji,Lan Huang,Yujing Yang,Xiaoyun Qiu,Shuo Zhang,Xuhong Jiang,Qiang Lv,Gang Cao,Yi Wang,Yingying Tang,Zhong Chen,Cenglin Xu
Background Status epilepticus (SE) is the most severe epilepsy type and exhibits a high resistance rate to the first-line therapy diazepam (DZP), which terms as refractory SE. Activated neuroinflammation is a key factor in the genesis of refractory SE. Gardeniae Fructus , a commonly used traditional Chinese herbal medicine, has been reported to exhibit anti-neuroinflammatory efficacies. Purpose In this study we aimed to evaluate the effects of Gardenia extract (GE) in two animal models of refractory SE and explore the mechanism of GE on SE. Methods We identified the main components of GE using LC-MS. The pilocarpine and KA-induced refractory SE models were established to evaluate the efficacy of GE. We used NeuN staining to observe the neuroprotective effects of GE. Then we employed network pharmacology to find potential therapeutic targets of GE. We verified the potential therapeutic mechanisms via western blot, immunohistochemistry, in vitro electrophysiological recording and pharmacological means. Results We identified thirteen main compounds, and demonstrated that combining GE with DZP could effectively terminate refractory SE induced by pilocarpine or kainic acid, with an extended therapeutic time window of up to 3h. GE also protected against neuronal injuries caused by refractory SE. Network pharmacology analysis suggested that inflammatory high mobility group box-1 (HMGB1) is a potential therapeutic target of GE. GE could reverse the upregulated expression and translocation of HMGB1 in mice with refractory SE and directly inhibited the enhancement of hippocampal excitatory synaptic transmission mediated by HMGB1 activation. Finally, GE was effective in terminating refractory SE caused by HMGB1 activation; whereas GE could not exhibit superior terminating efficacy when HMGB1 was pharmacologically inhibited. Conclusion These findings indicated for the first time that GE can terminate refractory SE by inhibiting HMGB1-induced neuroinflammation, highlighting its potential as a promising therapeutic strategy for this neurological emergency.
研究领域:
神经科学
·
药理学
·
中医药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Yu Yang,Zhe Chen,Guangli Yan,Ling Kong,Le Yang,Hui Sun,Ying Han,Jie Zhang,Xijun Wang
Insomnia is an accompanying symptom of many diseases and is closely associated with neurodegenerative diseases. Naoling Pian (NLP) is a patented Chinese medicine mainly used to treat insomnia. To evaluate the sedative and hypnotic effects of NLP and its modulatory effects on biological metabolites and metabolic pathways, rats with p-chlorophenylalanine (PCPA)-induced insomnia were given different doses of NLP by oral gavage for seven days. Diazepam (DZP) served as a positive control. Behavior was measured using the open field test, and neurotransmitter levels in the brain tissue related to sleep were measured using ELISA. The metabolic profiles and biomarkers of PCPA-induced insomnia in rats before and after NLP administration were analyzed using UPLC-Q/TOF-MS combined with multivariate data analysis. The results showed that the levels of 5-hydroxytryptamine, gamma-aminobutyric acid, norepinephrine, and dopamine in the brain tissue were significantly recovered in the NLP treatment groups, demonstrating similar or even superior therapeutic effects compared to the DZP group. The behavior of the PCPA-model rats partially recovered to normal levels after seven days of treatment. Metabolomics identified 30 metabolites in the urine as potential biomarkers of insomnia, and NLP significantly altered 25 of these, involving 21 metabolic pathways. NLP has a remarkable effect on insomnia, the therapeutic effects of which may be largely due to the rectification of metabolic disturbances. This is the first study of the sedative and hypnotic effects of NLP from a metabolomic perspective.
研究领域:
药理学
·
神经科学
·
代谢组学
·
中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LUMINESCENCE
·
2021
·Vol. 36
·期 8
·1997-2003
·
IF 2.464
Ziqi Zhou,Yige Gong,Chao Zhang,Weifen Niu
A chemiluminescence (CL) sensor array was developed based on 11 CL systems cross-combined by three luminescence reagents and four oxidants. Using the CL sensor array, we measured seven toxicants, including morphine, ketamine, diazepam, chlorpromazine, strychnine, paraquat, and fenpropathrin, which represent psychotropic drugs, sedatives and hypnotics, rodenticides, herbicides, and insecticides, respectively. The CL response pattern or ‘fingerprints’ were obtained for a given compound on the sensor array and then discriminated through principal component analysis. The established sensor array has been applied to real-life samples and the results showed that it possesses excellent discrimination.
研究领域:
分析化学
·
毒理学
·
环境科学
✓ 已验证
DOI
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Liu Wei,Chen Xiao,Zhao Jing,Yang Chen,Huang Guanqin,Zhang Zhen,Liu Jianjun
Alzheimer’s disease (AD) has an increasing prevalence, complicated pathogenesis and no effective cure. Emerging evidences show that flavonoid compounds such as xanthohumol (Xn) could play an important role as a dietary supplement or traditional Chinese herbal medicine in the management of diseases such as AD. This study aims to analyze the target molecules of Xn in the prevention and treatment of AD, and its potential mechanism from the perspective of metabolites. APP/PS1 mice 2- and 6-months old were treated with Xn for 3 months, respectively, the younger animals to test for AD-like brain disease prevention and the older animals to address therapeutic effects on the disease. Memantine (Mem) was selected as positive control. Behavioral tests were performed to assess the course of cognitive function. Urine samples were collected and analyzed by high-performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS) coupled with online Compound Discoverer software. Morris Water Maze (MWM) tests showed that Xn, like Mem, had a therapeutic but not a preventive effect on cognitive impairment. The expression levels of urinary metabolites appeared to show an opposite trend at different stages of Xn treatment, downregulated in the prevention phase while upregulated in the therapy phase. In addition, the metabolic mechanisms of Xn during preventive treatment were also different from that during therapeutic treatment. The signaling pathways metabolites nordiazepam and genistein were specifically regulated by Xn but not by Mem in the disease prevention stage. The signaling pathway metabolite ascorbic acid was specifically regulated by Xn in the therapeutic stage. In conclusion, dietary treatment with Xn altered the urinary metabolite profile at different stages of administration in APP/PS1 mice. The identified potential endogenous metabolic biomarkers and signal pathways open new avenues to investigate the pathogenesis and treatment of AD.
研究领域:
神经科学
·
药理学
·
代谢组学
·
疾病预防与治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Fuyuan Zhang,Jing Wang,Weihua Liu,Qingge Shi,Hangrui Liu,Yaxin Sang,Xianghong Wang
The presence of psychotropic drugs (PDs) in aquatic ecosystems represents an increasing environmental problem, posing a serious threat to human health and aquatic organisms. Lateral flow immunoassays (LFIA) have been widely used in the detection of PD contaminants. However, maintaining signaling tag reporting activity and achieving LFIA's multi-readout capability remain significant challenges to meeting a range of detection scenarios. Here, a rapid multifunctional LFIA has been developed for detecting diazepam (DAP), an emerging environmental and food safety PD contaminant, in lake water and fish samples. Copper hexacyanoferrate nanoparticles doped with Au and Pt (AuPt@Cu-HCF) were designed and manufactured as a multi-signal reporter with exceptional photothermal conversion efficiency and peroxidase-like enzymatic activity. This study integrates the colorimetric, photothermal, catalytic colorimetric, and catalytic photothermal effects of the AuPt@Cu-HCF nanozyme to form a “four-in-one” multi-readout LFIA. The multifunctional detection approach achieved four different detection signal outputs for DAP, with detection limits of 0.82 ng/mL, 12.82 pg/mL, 12.26 pg/mL, and 4.43 pg/mL for the basic colorimetric, photothermal, catalytic colorimetric, and colorimetric photothermal readout modes, respectively. This quadruplex-functional LFIA offers four different options with varying sensitivities and detection ranges, suitable for various application scenarios. It also allows multiple verifications for a single sample, enhancing detection accuracy.
研究领域:
环境科学
·
分析化学
·
纳米技术
·
食品安全
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ALZHEIMERS DISEASE
·
2023
·Vol. 92
·期 4
·1413-1426
·
IF 4
He Yan,Li Junjie,Yi Liling,Li Xiaohuan,Luo Man,Pang Yayan,Wang Maoju,Li Zhaolun,Xu Mingliang,Dong Zhifang,Du Yehong
Background:Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by amyloid-β peptide (Aβ) deposition. Aβ accumulation induces oxidative stress, leading to mitochondrial dysfunction, apoptosis, and so forth. Octadecaneuropeptide (ODN), a diazepam-binding inhibitor (DBI)-derived peptide, has been reported to have antioxidant properties. However, it is unclear whether ODN has neuroprotective effects in AD. Objective:To profile the potential effects of ODN on AD. Methods:We established a mouse model of AD via microinjection of Aβ in the lateral ventricle. Utilizing a combination of western blotting assays, electrophysiological recordings, and behavioral tests, we investigated the neuroprotective effects of ODN on AD. Results:DBI expression was decreased in AD model mice and cells. Meanwhile, ODN decreased Aβ generation by downregulating amyloidogenic AβPP processing in HEK-293 cells stably expressing human Swedish mutant APP695 and BACE1 (2EB2). Moreover, ODN could inhibit Aβ-induced oxidative stress in primary cultured cells and mice, as reflected by a dramatic increase in antioxidants and a decrease in pro-oxidants. We also found that ODN could reduce oxidative stress-induced apoptosis by restoring mitochondrial membrane potential, intracellular Ca2+ and cleaved caspase-3 levels in Aβ-treated primary cultured cells and mice. More importantly, intracerebroventricular injection of ODN attenuated cognitive impairments as well as long-term potentiation in Aβ-treated mice. Conclusion:These results suggest that ODN may exert a potent neuroprotective effect against Aβ-induced neurotoxicity and memory decline via its antioxidant effects, indicating that ODN may be a potential therapeutic agent for AD.
研究领域:
神经科学
·
药理学
·
分子生物学
·
神经退行性疾病
✓ 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）