BIOCHEMICAL PHARMACOLOGY
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2025
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IF 5.6
Sinuo Chen,Yifan Ma,Mingyan Ji,Heming Wang,Yun Chen,Dongping Li,Hongyue Jiang,Guangqi Song,Jinglin Xia,Hong Gao
Monocrotaline (MCT), a pyrrolizidine alkaloid (PA), is naturally found in certain plants and known for its hepatotoxic effects. In our prior research, we identified that phosphocreatine (PCr) mitigates PA-induced liver damage. However, the specific mechanism of PCr remains unknown. The objective of the present study was to elucidate the mechanism through which PCr shields against MCT-induced hepatic injury. In vitro assays demonstrated that PCr mitigated the MCT-induced ER stress and apoptosis. This alleviation was similarly observed with the use of the ER stress inhibitor 4-PBA, hinting at the role of ER stress in the protective mechanism of PCr against MCT-induced hepatic damage. In the MCT group, an upregulation of PSRC1 was evident, but this was notably downregulated following PCr treatment in vitro. The silencing of PSRC1 diminished the ER stress and apoptosis triggered by MCT, and the protective effect of PCr on liver injury remained evident. Overexpressing PSRC1 increased MCT-induced apoptosis and ER stress, and PCr still plays a protective role. In vivo experiments, we observed a notable attenuation of MCT-induced liver damage by PCr. Employing RNA sequencing and immunohistochemical staining techniques, we ascertained that endoplasmic reticulum (ER) stress, apoptosis and proline/serine-rich coiled-coil protein 1 (PSRC1) were significantly elevated in the liver samples treated with MCT. Notably, these alterations were counteracted by the presence of PCr. In conclusion, our findings suggest that PCr counteracts ER stress via modulation of PSRC1, which consequently confers protection against MCT-induced liver injury. Furthermore, this study offers potential therapeutic avenues for addressing hepatic damages attributable to MCT
研究领域:
毒理学
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肝脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2023
·Vol. 15
·期 19
·2334-2342
·
IF 3.1
Qian Li,Jing Yang,Wenzhan Yu,Liqiong He,Renlong Zhou,Changming Nie,Lifu Liao,Xilin Xiao
Monocrotophos (MP), an organophosphorus pesticide, poses a serious threat to human health, so a rapid and simple technique is needed to detect it. In this study, two novel optical sensors for MP detection were created using the Fe(III) Salophen complex and Eu(III) Salophen complex, respectively. One sensor is an Fe(III) Salophen complex (I-N-Sal), which can bind MP selectively and form a supramolecule, resulting in a strong resonance light scattering (RLS) signal at 300 nm. Under the optimum conditions, the detection limit was 30 nM, the linear range was 0.1–1.1 μM, the correlation coefficient R2 = 0.9919, and the recovery rate range was 97.0–103.1%. Interaction properties between the sensor I-N-Sal and MP and the RLS mechanism were investigated using density functional theory (DFT). And another sensor is based on the Eu(III) Salophen complex and 5-aminofluorescein derivatives. The Eu(III) Salophen complex was immobilized on the surface of amino-silica gel (Sigel-NH2) particles as the solid phase receptor (ESS) of MP and 5-aminofluorescein derivatives as the fluorescent (FL)-labeled receptor (N-5-AF) of MP, which can selectively bind the MP and form a sandwich-type supramolecule. Under the optimum conditions, the detection limit was 0.4 μM, the linear range was 1.3–7.0 μM, the correlation coefficient R2 = 0.9983, and the recovery rate range was 96.6–101.1%. Interaction properties between the sensor and MP were investigated by UV-vis, FT-IR, and XRD. Both sensors were successfully applied to the determination of MP content in tap water and camellia.
研究领域:
分析化学
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环境科学
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农药检测
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DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
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2023
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IF 3.6
Xiaofei Ren,Kui Xu,Jianming Xu,Qiao Mei
Melatonin possesses potent hepatoprotective properties, but it remains to be elucidated whether melatonin has a therapeutic effect on monocrotaline (MCT)-induced hepatic sinusoidal obstruction syndrome (HSOS). In this study, male Sprague Dawley rats were intraperitoneally injected with melatonin or the same volume of vehicle at 0 and 24 h after MCT intragastric administration. Next, hematoxylin–eosin staining and electron microscopy were performed to evaluate the hepatic sinusoidal injury of rats. Endothelial cell marker RECA-1 was observed by immunohistochemistry. Hepatic oxidative stress was analyzed by detecting malondialdehyde, glutathione S-transferase, and reactive oxygen species. Assessment of liver function was carried out by analysis of serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin levels. Real-time polymerase chain reaction and Western blot analysis were used to identify liver Sirtuin-3 (SIRT3) and active matrix metallopeptidase 9 (MMP-9) expression. Besides, liver sinusoidal endothelial cells (LSECs) were used for the in vitro functional verification experiment. Specifically, liver histology of the melatonin-treated groups showed that the pathological damages caused by MCT were significantly attenuated, total HSOS scores were decreased, and the elevation of serum hyaluronic acid observed in the model group was also reduced. Moreover, melatonin treatment also improved the survival of rats after partial hepatectomy. Administration of melatonin ameliorated MCT-induced LSECs injury, hepatic oxidative stress, and hepatic dysfunction. Furthermore, melatonin treatment increased SIRT3 expression while attenuating MMP-9 activity in liver tissues. Cell experiment also demonstrated that SIRT3 might mediate the protective effect of melatonin on LSECs. Collectively, our study provided the potential rationale for the application of melatonin for the prevention of MCT-induced HSOS.
研究领域:
药理学
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肝病学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Clinical and Translational Hepatology
·
2024
·Vol. 13
·期 1
·25
·
IF 3.1
Mingyan Ji,Yun Chen,Yifan Ma,Dongping Li,Jin Ren,Hongyue Jiang,Sinuo Chen,Xiaoqing Zeng,Hong Gao
Background and Aims Pyrrolizidine alkaloids (PAs), widely distributed in plants, are known to induce liver failure. Hepatic platelet accumulation has been reported during the progression of PA-induced liver injury (PA-ILI). This study aimed to investigate the mechanisms underlying platelet accumulation in PA-ILI. Methods Cases of PA-ILI, non-PA-ILI, and control subjects were collected from patients hospitalized at Zhongshan Hospital, Fudan University (Shanghai, China) between 2012 and 2019. A mouse model of PA-ILI was established using monocrotaline administration. Liver RNA sequencing was performed, and gene interactions were analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins online database. Low-molecular-weight heparin and recombinant a disintegrin and metalloproteinase with a thrombospondin type I motif member 13 (ADAMTS13) were applied. The necrotic liver area, hepatic platelet accumulation, and von Willebrand factor (VWF) deposition were examined using hematoxylin and eosin staining and immunofluorescence assay. Results Hepatic platelet accumulation, necrotic area expansion, and increased VWF expression were observed in both PA-ILI patients and mice. The Search Tool for the Retrieval of Interacting Genes/Proteins database indicated that ADAMTS13 regulates VWF expression and was differentially expressed in the livers of PA-ILI mice. Plasma and hepatic ADAMTS13 levels were significantly downregulated in both PA-ILI patients and mice. Systemic administration of recombinant ADAMTS13 decreased hepatic platelet accumulation, downregulated VWF expression, and mitigated mouse hepatic necrosis. Conclusions Hepatic platelet accumulation in PA-ILI was confirmed in both patients and mice. Deficiency of ADAMTS13 plays a critical role in platelet accumulation in PA-ILI, suggesting that ADAMTS13 could be a potential therapeutic target for this condition.
研究领域:
肝病学
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药理学
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分子生物学
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病理学
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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
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2014
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IF 2.694
Zhiyong Zhao,Qinxiong Rao,Suquan Song,Na Liu,Zheng Han,Jiafa Hou,Aibo Wu
A simple and reliable method for simultaneous determination of deoxynivalenol-3-glucoside and major type B trichothecenes (deoxynivalenol, nivalenol, fusarenon X, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol and deepoxy-deoxynivalenol) in animal feed and raw materials has been developed and validated in this study. The method was based on an improved dispersive solid-phase extraction (DSPE) followed by analysis using high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Also, matrix-matched calibration curve ( R 2 > 0.99) was employed to minimize matrix effects and ensure accurate quantification. The recoveries during sample preparation process (including extraction and clean-up) ranged from 79.03% to 118.39%, with intra-day and inter-day relative standard deviation lower than 20% for all the analytes. The limit of quantification ranged from 5.0 μg/kg for deoxynivalenol to 13.6 μg/kg for fusarenon X. The validated method was successfully applied to the analysis of animal feed and corn. The pilot study showed that 37 out of 41 samples were contaminated with deoxynivalenol-3-glucoside at the levels of 6.0–121.0 μg/kg. Most of the type B trichothecenes were also found with the exception of fusarenon X, at the contaminated levels of 10.0–1382 μg/kg. To the best of our knowledge, this was the first scientific report on the co-occurrence of masked deoxynivalenol and type B trichothecenes in animal feed and raw materials.
研究领域:
食品安全
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分析化学
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产品关联
DOI
PubMed
高影响因子
IMMUNOLOGY LETTERS
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2025
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IF 2.8
Xing Chen,Lixiang Li,Yan Deng,Juan Liao,Hui Meng,Limei Liang,Jie Hu,Dongwei Xie,Guizi Liang
(1) Background Metabolic abnormalities and immune inflammation are key elements within pathogenesis of pulmonary arterial hypertension (PAH). And in PAH patients, aberrant glutamine metabolism has been observed; however, the function of glutaminase 1 (GLS1) in macrophage is still unknown. So we aims to investigate GLS1′s impact upon macrophages in PAH. (2) Methods We firstly constructed an monocrotaline (MCT)-induced PAH rat model. Briefly, the PAH rats were treated with the GLS1 inhibitor BPTES, and various index were evaluated, including hemodynamics, right ventricular function, pulmonary vascular remodeling, macrophage markers, and glutamine metabolism. After that, we polarized bone marrow-derived macrophages (BMDMs) into M1 phenotype and then subjected to BPTES intervention. Finally, we assessed macrophage phenotype, inflammatory markers, and glutamine metabolism indicators, along with the impact of BMDM supernatant on the behavior of pulmonary arterial smooth muscle cells (PASMCs). (3) Results : GLS1 was significantly upregulated in both PAH patients and rats. Treatment with the GLS1 inhibitor BPTES markedly improved pulmonary arterial pressure, right ventricular function, and pulmonary vascular remodeling in PAH rats, while inhibiting M1 macrophage polarization, NLRP3 activation, and the release of pro-inflammatory cytokines. This, in turn, alleviated the proliferation and migration of PASMCs induced by inflammatory stimuli. (4) Conclusion : We propose that targeting GLS1 to reduce M1 macrophage polarization and inflammatory responses may represent a promising therapeutic approach for PAH.
研究领域:
心血管疾病
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免疫学
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药理学
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细胞生物学
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代谢
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产品关联
DOI
PubMed
高影响因子
LUNG
·
2022
·Vol. 200
·期 5
·619-631
·
IF 3.777
Zhai Cui,Zhang Nana,Wang Jian,Cao Meng,Luan Jing,Liu Huan,zhang Qianqian,Zhu Yanting,Xue Yuxin,Li Shaojun
Purpose It has been shown that activation of autophagy promotes the development of pulmonary arterial hypertension (PAH). Meanwhile, forkhead box M1 (FOXM1) has been found to induce autophagy in several types of cancer. However, it is still unclear whether FOXM1 mediates autophagy activation in PAH, and detailed mechanisms responsible for these processes are indefinite. Method PAH was induced by a single intraperitoneal injection of monocrotaline (MCT) to rats. The right ventricle systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), percentage of medial wall thickness (%MT), α-smooth muscle actin (α-SMA) staining, and Ki67 staining were performed to evaluate the development of PAH. The protein levels of FOXM1, phospho-focal adhesion kinase (p-FAK), FAK, and LC3B were determined by immunoblotting or immunohistochemistry. Results FOXM1 protein level and FAK activity were significantly increased in MCT-induced PAH rats, this was accompanied with the activation of autophagy. Pharmacological inhibition of FOXM1 or FAK suppressed MCT-induced autophagy activation, decreased RVSP, RVHI and %MT in MCT-induced PAH rats, and inhibited the proliferation of pulmonary arterial smooth muscle cells and pulmonary vessel muscularization in MCT-induced PAH rats. Conclusion FOXM1 promotes the development of PAH by inducing FAK phosphorylation and subsequent activation of autophagy in MCT-treated rats.
研究领域:
心血管疾病
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药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2021
·
IF 13.273
Yang Zhong,Jiayu Gu,Yaoquan Su,Lingzhi Zhao,Yunyun Zhou,Juanjuan Peng
Herbal medicines and dietary supplements are widely used worldwide. However, reports have revealed that a large number of herbal medicines are implicated in the hepatic damage, which is referred to as Herbal medicines-induced liver injury (HILI). Traditional diagnostic methods for HILI include histological and serological assessments, which fail to offer real-time and unambiguous visualization of hepatotoxicity in vivo . Herein, we constructed a second near-infrared (NIR-II) luminescent nanoprobes to achieve accurate, high-efficiency, and non-invasive detection of HILI by the assembly of lanthanide-based NIR-II luminescence nanoparticles with a chromophore with absorption band in the NIR-II region. Specifically, the NIR-II luminescence of the lanthanide nanoparticles can be effectively quenched by the chromophores on the surface of nanoparticles via an absorption competition-induced quenching effect, and subsequently recovered by the pathophysiological biomarker peroxynitrite (ONOO − ) generated in early HILI. It is demonstrated that the nanoprobes are capable for the screening of liver toxins in a noninvasive pattern, which is more convenient than the conventional diagnostic approaches. Finally, our luminescence detection approach offers an immediate testing technique for the identification of hepatotoxic components of herbal medicine such as colchicine, monocrotaline and stibene glucoside, providing a high-throughput screening strategy for herbal medicine-induced hepatotoxicity.
研究领域:
药理学
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毒理学
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生物医学工程
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分析化学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）