MICROCHEMICAL JOURNAL
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2024
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IF 4.9
Chaoqun Fei,Shulan Qi,Jiahuan Zhang,Shi Zhou,Yingxue Guo,Yanli Zhao,Jiazheng Jin,Jinlian Li,Ximing Cui,Dongmei Wu
As industrialization accelerates, there is an increasing need to find a quick, easy, and affordable method to assess the potential DNA damage caused by newly developed chemicals. Electrochemical voltammetry using intracellular purine bases as markers shows promise for detecting DNA damage. However, it is unclear whether drugs with different DNA damage mechanisms will impact purine metabolism in cells and consequently disturb the electrochemical indicators of DNA damage. In this paper, the electrochemical behaviors of HepG2 cells exposed to the direct DNA-damaging agent (MNNG), the indirect DNA-damaging agent (CPT11), and the non-DNA-damaging agent (KCl) were studied. The findings showed that the electrochemical signals of cells increased with the rising concentration of DNA-damaging drugs. A time-dependent effect was observed, with a lower threshold dose for 4 h compared to 1 h. However, the non-DNA-damaging agent did not induce an increase in the cellular electrochemical signal. Despite the higher cytotoxicity of CPT11, MNNG triggered DNA damage at a lower dose, as detected by electrochemical indicators. The results of the electrochemical indicators assessment of DNA damage correlated significantly with those of the γH2AX focus and alkaline comet assays, with r > 0.98 and P < 0.01. Particularly, there was a stronger correlation with the alkaline comet assay. Furthermore, electrochemical voltammetry detected DNA damage at a lower threshold compared to other assessment methods, demonstrating a higher sensitivity to DNA damage. These findings suggest that by using purine bases as markers, electrochemical voltammetry enables precise assessment of DNA damage caused by various mechanisms.
研究领域:
毒理学
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药理学
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分子生物学
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生物医学工程
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产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Yanning Zhu,Ruyun Ma,Wen Cheng,Mengyao Qin,Weiheng Guo,Ying Qi,Jianye Dai
Ethnopharmacological relevance Sijunzi decoction (SJZD), a traditional Chinese medicine formula, is commonly used in clinical practice for the treatment of gastric precancerous lesions (GPL). However, the mechanism of gastric protection is not fully understood. Aims of the study The purpose of this study was to systematically evaluate the efficacy of SJZD in blocking the development of GPL and to reveal the underlying mechanism. Methods First, we established a rat model of GPL, which was induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) combined with an irregular diet and 40% ethanol. The efficacy of SJZD was evaluated based on pathological sections and serum biochemical indices. Then, the pharmacodynamic mechanism of SJZD was revealed by quantitative proteomics based on stable isotope dimethyl labeling. At the same time, the pharmacodynamic mechanism was verified by quantitative metabolomics. In addition, the anti-gastritis effect of SJZD was confirmed by a serum pharmacology method in a cell model, and the functional mechanism was further verified. Results We demonstrated that SJZD could block the development of GPL in the animal model. Proteomics and metabolomics revealed that SJZD blocks GPL development by regulating oxidative phosphorylation (OXPHOS). In addition, the serum pharmacology results showed that SJZD-containing serum (SJZD-CS) could inhibit apoptosis in MNNG-induced GES-1 cells. OXPHOS inhibitors could significantly reduce the protective effect of SJZD-CS. Conclusion SJZD effectively ameliorates GPL, and proteomics and metabolomics revealed that its protective effects are closely related to OXPHOS.
研究领域:
民族药理学
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药效学
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蛋白质组学
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代谢组学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
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2024
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IF 2.7
Lei Zhu,Qingxin Cai,Gang Li,Xiaoming Zou
Objective Gastric precancerous lesions (GPL), characterized by intestinal metaplasia and dysplasia, marks a pivotal juncture in the transformation from gastritis to gastric cancer. Research on GPL could offer fresh perspectives on preventing cancer occurrence. Methods This study employed 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) to establish GPL rat models and knocked BRD4 down in vivo to assess its impact on the lesions and macrophage morphology. Following that, the impacts of BRD4 knockdown on the malignant phenotypes of human gastric epithelial GES-1 cells were determined. Moreover, conditioned medium from macrophage was gathered and used for GES-1 cell culture. The involvement of macrophage polarization in the BRD4 regulatory mechanism in GES-1 cells was assessed. Results This study elucidated that MNNG induced an increase level of BRD4 in the rat models. BRD4 knockdown reduced lesions based on pathological sections and immunohistochemistry to detect proliferative antigens. Western blotting and immunofluorescence showed that BRD4 knockdown suppressed epithelial-mesenchymal transition and macrophage M2 polarization. In in vitro experiments, BRD4 knockdown inhibited the malignant phenotype of GES-1 cells and the differentiation of THP-1 cells into M2 macrophages, respectively. The conditioned medium from M2 macrophages with BRD4 knockdown was co-incubated with GES-1 cells, which attenuated the malignant phenotypes compared with the medium from M2 macrophages. Conclusion: Through in vivo and in vitro experiments, BRD4 upregulation was found to already occur during GPL, affecting macrophage polarization and epithelial cell cancerization. This finding provides an experimental basis for strategies targeting BRD4 inhibition at this critical stage.
研究领域:
肿瘤学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Yuxi Guo,Xuemei Jia,Pengli Du,Jie Wang,Yao Du,Bolin Li,Yucong Xue,Jianming Jiang,Yanru Cai,Qian Yang
Ethnopharmacological relevance Xianglianhuazhuo formula (XLHZ) has a potential therapeutic effect on chronic atrophic gastritis (CAG). However, the specific molecular mechanism remains unclear. Aim of the study To evaluate the effect of XLHZ on CAG in vitro and in vivo and its potential mechanisms. Methods A rat model of CAG was established using a composite modeling method, and the pathological changes and ultrastructure of gastric mucosa were observed. YY1/miR-320a/TFRC and ferroptosis-related molecules were detected. An MNNG-induced gastric epithelial cell model was established in vitro to evaluate the inhibitory effect of XLHZ on cell ferroptosis by observing cell proliferation, migration, invasion, apoptosis, and molecules related to ferroptosis. The specific mechanism of action of XLHZ in treating CAG was elucidated by silencing or overexpression of targets. Results In vivo experiments showed that XLHZ could improve the pathological status and ultrastructure of gastric mucosa and inhibit ferroptosis by regulating the YY1/miR-320a/TFRC signaling pathway. The results in vitro demonstrated that transfection of miR-320a mimics inhibited cell proliferation, migration, and invasion while promoting cell apoptosis. MiR-320a targeted TFRC and inhibited ferroptosis. Overexpression of TFRC reversed the inhibitory effect of miR-320a overexpression on cell proliferation. The effect of XLHZ was consistent with that of miR-320a. YY1 targeted miR-320a, and its overexpression promoted ferroptosis. Conclusion XLHZ inhibited ferroptosis by regulating the YY1/miR-320a/TFRC signaling pathway, ultimately impeding the progression of CAG.
研究领域:
民族药理学
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分子生物学
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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