BIOMEDICAL CHROMATOGRAPHY
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2022
·Vol. 37
·期 2
·e5535
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IF 1.911
Jiayin Liu,Yang An,Jun Su,Qinghai Dong,Hongliu Xie,Jihua Liu
In this study, a new compound PPD-Arg (Tos) (PAT), an arginine derivative of 20(s)-PPD, was synthesized via Fmoc-Arg (Tos)-OH and 20(s)-PPD. The pharmacokinetic properties in rats, in vitro cytotoxicity, and cell apoptosis rates of protopanaxadiol (PPD) and PAT were determined. A sensitive bioanalytical method for pharmacokinetics using ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry was developed and validated. The result showed that the T max and t 1/2 of PAT were significantly enhanced, indicating a long-lasting effect in vivo . Compared to the PPD group, the PAT group showed higher bioavailability. PAT also exhibited higher antitumor efficacy than PPD against three cancer cells, especially the strongest inhibitory activity against Huh-7, even more potent than the positive control of paclitaxel. Therefore, the apoptosis assay based on annexin V/propidium iodide–combined staining against Huh-7 further demonstrated that PAT could induce apoptosis of Huh-7 cells. Better pharmacokinetic properties and antitumor efficacy of the arginine derivative of 20(s)-PPD were important. These findings could provide references for further clinical research on amino acid derivatives of PPD as antitumor agents.
研究领域:
药理学
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肿瘤学
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分析化学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2022
·
IF 5.195
Fangfang Xu,Jun Wang,Pan Wang,Tao Hou,Han Zhou,Yaopeng Zhao,Jixia Wang,Yanfang Liu,Xinmiao Liang
Ursodeoxycholic acid (UDCA) is a safe bile acid effective in reducing hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). However, the mechanism of action linked to this effect is poorly defined. In the present study, we identified that UDCA acted as a free fatty acid receptor 4 (FFA4) agonist with EC 50 of 10.4 ± 0.7 μM, and its activity was determined by dynamic mass redistribution, fluorometric imaging plate reader, inositol monophosphate and bioluminescence resonance energy transfer assays. Moreover, UDCA showed FFA4 selectivity over eleven other G protein-coupled receptors. Real-Time PCR and immunocytochemistry analyses showed that FFA4 was abundantly expressed in human hepatocytes HuH-7 cells. In an in vitro model of NAFLD induced by oleic acid (OA), UDCA downregulated lipid accumulation in HuH-7 cells and suppressed sterol-regulatory element binding protein-1c (SREBP-1c) mRNA expression. This suppression of SREBP-1c was restored when FFA4 expression was knocked down in siRNA assay. In a mouse model of hepatic steatosis, db/db mice were exposed to a high-fat diet (HFD), and treatment of UDCA or docosahexaenoic acid (DHA, an endogenous FFA4 agonist) effectively prevented body weight gain and hepatic fat deposition and reduced triglyceride (TG) levels in serum and liver. This study not only identified a new skeleton of FFA4 agonists, but also demonstrated that FFA4 signal was accounting for the protective effects of UDCA in the NAFLD treatment.
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
PHYTOMEDICINE
·
2023
·
IF 7.9
Qi-Rui Hu,Qing-Xin Huang,Huan Hong,Yao Pan,Ting Luo,Jing Li,Ze-Yuan Deng,Fang Chen
s Background Liver cancer is a topical global health issue. The treatment of liver cancer meets significant challenges in the high recurrence rate and invasive incidence. Therefore, the treatment strategies that target epithelial-mesenchymal transition (EMT) induced by cyclooxygenase 2 (COX2)/ prostaglandin E2 (PGE2) pathway have become epidemic. Ginsenoside Rh2 has been proved to inhibit the EMT. However, the underlying mechanisms remain unclear. Moreover, the octyl ester derivative of Rh2 (Rh2-O) exhibited superior anti-proliferative and immunomodulatory effects than Rh2 in our previous researches, which indicated that Rh2-O might also exert inhibitory effects on invasion and metastasis . Purpose The aim of current study is to explore the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis of hepatocellular carcinoma , and to investigate whether these effects are dependent on the c-Jun/COX2/PGE2 pathway. Study Design The Huh-7 liver cancer cells and the H22 tumor-bearing mice were treated with Rh2 and Rh2-O. Method In this paper, the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis were tested by wound healing, trans-well assay and tumor-bearing mice, and the involvement of c-Jun/COX2/PGE2 pathway were verified by exogenous PGE2, activation of COX2 and overexpression of c-Jun. Results The results showed that Rh2 and Rh2-O could efficiently inhibit the invasion and metastasis in a dose-dependent manner ( p < 0.05). And the Rh2-O showed stronger effects than Rh2. Moreover, the exogenous PGE2, activation of COX2 by exogenous LPS and the overexpression of c-Jun by transfection all reversed the inhibitory effects of Rh2 and Rh2-O on metastasis or EMT ( p < 0.05). Conclusion Rh2 and Rh2-O could inhibit the invasion and metastasis of hepatocellular carcinoma via restraining the EMT, which was mediated by c-Jun/COX2/PGE2 pathway.
研究领域:
肿瘤学
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药理学
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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 APPLIED POLYMER SCIENCE
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2024
·
IF 2.7
Yonghua Zhai,Lili Wu,Jie Gao,Jingsheng Zhou,Longhai Du,Xiaoda Fu,Yang Gao,Tinglin Zhang,Mengya Zhang,Weihong Lu,Yan Wu
Smart gene delivery vectors are gaining increasing attention in gene therapy, owing to their low cytotoxicity and intrinsic responsiveness. Our previously fabricated novel cationic brush polymer, comprising C Se bonds and tertiary amine EGIn- g -PDMAEMA, shows potential for gene transfection. In this study, its high efficiency for siRNA/pDNA transfection and low cytotoxicity in reactive oxygen species (ROS)-rich microenvironments is substantiated in vitro. Its superior binding capacity with siRNA/pDNA is confirmed by agarose gel electrophoresis assay. The threshold weight ratios for siRNA/pDNA migration delay are 15 and 3 (polymer-to-nucleic acid, w/w), respectively. Fluorescence microscopy and ribonucleotide reductase regulatory subunit M2 gene silencing essay verify the biodegradability and responsive control release of nucleic acids under hydrogen peroxide stimulation in Huh-7 cells. Compared with the gold standard, polyethylenimine 25 kDa, the target polymer displays superior transfection efficiency in ROS-rich tumor cells under serum-free conditions. Furthermore, the vector–nucleic acid complexes exhibit over 90% cell viability at a high concentration of 12 μg mL −1 and good colloidal stability in phosphate-buffered saline (PBS) and 10% fetal bovine serum-PBS for 24 h. The efficient control release and expression of nucleic acids in ROS environments and reduced cytotoxicity highlight the superiority of EGIn- g -PDMAEMA as a gene delivery platform for tumor gene therapy.
研究领域:
生物医学工程
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基因治疗
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材料科学
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分子生物学
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DOI
高影响因子
ENVIRONMENTAL POLLUTION
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2024
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IF 7.6
Xuewen Yao,Zhaokang Cheng,Evgenios Agathokleous,Yaqian Wei,Xinyuan Feng,Hanhan Li,Tingting Zhang,Shuting Li,Gaurav Dhawan,Xiao-San Luo
As typical antibiotics, tetracycline (TC) and sulfadiazine (SDZ) enter the human body through the food chain. Therefore, it is necessary to understand their individual and combined toxicity. In this study, the effects of TC, SDZ, and their mixture on cell viability, cell membrane damage, liver cell damage, and oxidative damage were evaluated in in vitro assays with human liver cells Huh-7. The results showed cytotoxicity of TC, SDZ, and their mixture, which induced oxidative stress and caused membrane and cell damage. The effect of antibiotics on Huh-7 cells increased with increasing concentration, except for lactate dehydrogenase (LDH) activity that commonly showed a threshold concentration response and cell viability, which commonly showed a biphasic trend, suggesting the possibility of hormetic responses where proper doses are included. The toxicity of TC was commonly higher than that of SDZ when applied at the same concentration. These findings shed light on the individual and joint effects of these major antibiotics on liver cells, providing a scientific basis for the evaluation of antibiotic toxicity and associated risks.
研究领域:
药理学
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毒理学
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细胞生物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
ARCHIV DER PHARMAZIE
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2024
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IF 4.3
Jiahong Su,Xingyue Wang,Sha Li,Xu Wu,Mingxing Li,Fukuan Du,Shuai Deng,Jing Shen,Yueshui Zhao,Zhangang Xiao,Yu Chen
Glycyrrhetinic acid (GA) is a naturally occurring triterpene compound. The aim of this study was to employ the pharmacophore hybrid strategy to merge GA with various dithiocarbamates and obtain novel compounds with better antitumor activities. We present a two-step synthetic protocol wherein the GA derivative underwent reaction with carbon disulfide and various secondary amines in a one-pot manner under mild conditions, facilitating the preparation of a series of structurally novel GA-dithiocarbamate derivatives. Bioassay screening revealed that the representative compound 3c demonstrated the capacity to reduce the mitochondrial membrane potential in Hep3B and Huh-7 cells, induce nuclear apoptosis, inhibit invasion and migration, and prompt both early and late apoptosis. Furthermore, our research findings indicated that this apoptotic phenomenon may be associated with the expression of Bcl-2, Bax, Bak, PARP, and cleaved-PARP proteins. Utilizing network pharmacology for predicting core targets and signaling pathways of compound 3c for hepatocellular carcinoma (HCC) treatment involved employing molecular docking models to demonstrate high affinity between compound and target protein. In conjunction with Western blot analysis, compound 3c may impact HCC through the PI3K-AKT-mTOR pathway.
研究领域:
药理学
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肿瘤学
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药物化学
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2020
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IF 3.69
Meijing Liu,Guohui Zhang,Shuangcheng Wu,Meng Song,Jueyu Wang,Weibin Cai,Suiqing Mi,Changhui Liu
Ethnopharmacology relevance The farnesoid X receptor (FXR) is a therapeutic target of for the treatment of non-alcoholic fatty liver disease (NAFLD) owing to its regulatory role in lipid homeostasis. Schaftoside (SS) is a bioactive compound of Herba Desmodii Styracifolii , which has traditionally been used to treat hepatitis and cholelithiasis . However, the potential hepatoprotective effect of SS against NAFLD and the underlying mechanisms remain unknown. Aim of the study We investigated whether SS could improve NAFLD-induced liver injury by decreasing lipid accumulation via the activation of FXR signalling. Materials and methods In vivo , the effects of SS on high-fat diet (HFD)-induced lipid accumulation in the liver of mice were evaluated by serum biochemical parameters and histopathological analysis. In vitro , the intracellular triglyceride (TG) level and Oil Red O staining were used to evaluate the lipid removal ability of SS in Huh-7 cells or FXR knockout mouse primary hepatocytes (MPHs) induced by oleic acid (OA). Moreover, FXR/sterol regulatory element-binding protein 1 (SREBP1) mRNA and protein expression levels were detected. Results SS reduced HFD-induced lipid accumulation in the liver, as indicated by decreased aspartate aminotransferase (AST), cholesterol (Ch), and TG levels in serum and TG levels in liver tissue, and subsequently resulting in attenuation of liver histopathological injury. Gene expression profiles demonstrated that SS dose-dependently prevented HFD-induced decrease of FXR expression and inversely inhibited SREBP1 expression in the nucleus. Furthermore, SS significantly suppressed excessive TG accumulation and decreased intracellular TG level in Huh-7 cells or MPHs via the upregulation of FXR and inhibition of SREBP1 expression in the nucleus. Conclusion Our results suggest that SS ameliorates HFD-induced NAFLD by the decrease of lipid accumulation via the control of FXR-SREBP1 signalling.
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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民族药理学
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Zhihao Zhang,Feng Liu,Xin Lan,Fuhai Wang,Jiahao Sun,Honglong Wei
Objective This study explores the impact of pyroptosis-related genes (PRG) on the prognosis of liver cancer (LC). Methods 421 samples (371 tumor samples and 50 normal samples) from the Cancer Genome Atlas (TCGA) were included in this study. GSE14520 dataset (data of RNA expression and relevant clinicopathological features), GSE125449 dataset (single-cell data in LC) and HCCDB18 dataset (validation on the reliability of the model) were downloaded as appropriate. Download the PRG and its corresponding pathway information from the gene set enrichment analysis (GSEA) website. The consensus clustering was performed by ConsensusClusterPlus package. Differentially expressed genes (DEGs) were identified using limma package, and prognostic features were constructed using un/multivariate and Lasso Cox regression. Pathway enrichment analysis was conducted by ssGSEA method. Receiver Operating Characteristic and the survival analysis were conducted by timeROC and Survminer packages. The Seurat package was used for single-cell RNA sequencing (scRNA-seq) analysis. For cellular validation, following the quantification on the key genes via reverse-transcription quantitative PCR, the Transwell and scratch assays were applied to evaluate the in-vitro invasion and migration of LC cells Huh-7. Results 12 prognosis-related genes were identified to be related to the progression of LC. Three subtypes including C1, C2 and C3 were categorized using the 12 prognosis-related genes and PRGs significantly related to the prognosis of LC patients. The worst and best prognosis was seen in C3 subtype and C2 subtype, respectively. Hallmark pathway enrichment analysis has shown the concurrent immunoactivation and immune escape in C3 subtype. A RiskScore model was constructed using 8 key genes (KPNA2, UCK2, FTCD, CBX2, RAB32, HMMR, S100A9 and ANXA10) from the DEGs of three subtypes. The RiskScore system as an independent prognostic factor dividing the patients into high and low risk groups, and patients of the high-risk group had poor prognosis in both test set and validation set. A nomogram model combining the risk score had the extreme higher benefit. Further, 6 subclusters were identified from scRNA-seq analysis, where the highest PYROPTOSIS score was seen in Monocytic-Macrophages. The quantification on the key genes has suggested the high expressions of KPNA2, UCK2, CBX2, RAB32, HMMR and S100A9 and the low expressions of FTCD and ANXA10 in LC cells Huh-7. Particularly, UCK2 knockdown evidently diminished the number of invaded and migrated LC cells in vitro . Conclusion The risk model associated with pyproptosis is crucial for the tumor immunity of LC and may serve as a prognostic indicator for patients suffering from LC. Our findings will offer new perspectives for immunotherapies targeting LC.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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癌症基因组学
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细胞免疫学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Jingbo Sun,Hongchen Li,Min Ouyang,Jing Cheng,Dong Xu,Xiaofeng Tan,Qinlu Lin
Cytoarchitectural staining is of great importance in disease diagnosis and cell biology research. This study developed user-friendly multifunctional red-emissive carbon dots (R-CDs) for rapid cell nucleus staining via targeting nuclear proteins. R-CDs, simply prepared by electrochemical treatment of 1,2,4-benzenetriamine, exhibit strong emission at 635 nm when excited at 507 nm. The R-CDs can rapidly stain the nucleus of human SH-SY5Y, HepG2, and HUH-7 cells with a high signal-to-noise ratio owing to fluorescence enhancement after entering the nucleus. Compared to conventional cytosolic dyes such as Hoechst and DAPI, R-CDs are cheaper, more highly dispersed in water, and more stable (requiring no stringent storage conditions). The R-CDs show stable optical properties with insignificant photobleaching over 7 days and salt resistance up to 2 M of NaCl. More importantly, R-CDs, possessing a positive charge, allow rapid staining of live cells (3 min) and dead cells (10 s) in saline. According to kinetic variation, R-CDs can distinguish live cells from dead cells. Staining exhibits high efficiency in onion epidermal cells, Aspergillus niger, Caenorhabditis elegans, and human spermatozoa. The mechanism for efficient staining is based on their fast accumulation in the nucleus due to their small size and positive charge and strong interaction with nuclear proteins at amino acid residues of histidine and arginine, resulting in fluorescence enhancement by dozens of times. The developed R-CDs do not bind to DNA and would not cause genetic damage and will find various safe applications in biological and medical fields.
研究领域:
细胞生物学
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疾病诊断
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材料科学
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光学性质
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生物医学应用
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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