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Environmental Technology & Innovation · 2024 · IF 6.7

Trivalent chromium stress trigger accumulation of secondary metabolites in rice plants: Integration of biochemical and transcriptomic analysis

Yi Kang,Yu-Juan Lin,Ullah Abid,Fei-Fei Zhang,Xiao-Zhang Yu

Trivalent chromium [Cr (III)] is a frequently detected environmental contaminant that negatively affects plant metabolism, growth, and yield. Plant secondary metabolites are non-nutrient compounds involved in diverse physiological functions in response to abiotic stresses. This study performed biochemical and transcriptomic analyses to clarify the protective role and mechanisms of secondary metabolites in rice seedlings under Cr(III) stress. The content of measured secondary metabolites i.e., total soluble phenolics, flavonoids, lignin, and anthocyanin in rice tissues was significantly enhanced under Cr(III) exposure. Additionally, the activities of several enzymes including chalcone synthase, phenylalanine ammonialyase, peroxidase, and anthocyanidin synthase, were positively activated. Transcriptomic analysis revealed a number of differentially expressed genes (DEGs) in Cr(III)-treated rice seedlings and their expression patterns are tissue-specific. Additionally, the DEGs involved in secondary metabolism pathways were evident after KEGG enrichment analysis. Cr(III) exposure resulted in distinct genetic regulation strategies in rice tissues, with different DEGs activating various sub-pathways in the secondary metabolism pathways to cope with Cr(III) stress. Furthermore, the integrated correlation analysis of the secondary metabolites and transcriptome data identified key genes involved in different steps of the sub-pathways of secondary metabolism pathway in rice plants under Cr(III) stress. This study indicates that the accumulation of secondary metabolites in rice plants is a survival and detoxification strategy to reduce the adverse effects of toxic compounds. Future research should explore how key genes in secondary metabolism pathways aid in Cr(III) detoxification and enhance crop stress tolerance.

CAS / MDL: 13548-38-4
研究领域: 植物生理学 · 环境毒理学 · 分子生物学 · 生物化学
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Processes · 2024 ·Vol. 12 ·期 4 ·687 · IF 2.8

Differential Analysis of Pomelo Peel Fermentation by Cordyceps militaris Based on Untargeted Metabolomics

Yannan Xiang,Siyi Tian,Xinyu Luo,Chenggang Cai,Yaowen Du,Hailong Yang,Haiyan Gao

The content of differentially abundant metabolites in the fermentation broth of grapefruit peels fermented byCordyceps militarisat different fermentation times was analyzed via LC–MS/MS. Small molecule metabolites and differential metabolic pathways were analyzed via multivariate analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. A total of 423 metabolites were identified at 0, 2, 6, and 10 days after fermentation. Among them, 169 metabolites showed differential abundance, with significant differences observed between the fermentation liquids of every two experimental groups, and the metabolite composition in the fermentation liquid changed over the fermentation time. In summary, the upregulation and downregulation of metabolites in cancer metabolic pathways collectively promote the remodeling of cancer cell metabolism, facilitating increased glycolysis, alterations in TCA cycle flux, and enhanced biosynthesis of the macromolecules required for rapid proliferation and survival. This study provides new perspectives on the development of high-value-added agricultural and forestry byproducts and the development and research of functional foods.

研究领域: 食品科学 · 微生物学 · 代谢组学 · 药理学
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Frontiers in Pharmacology · 2021 · IF 5.811

An Integrated Strategy for Effective-Component Discovery of Astragali Radix in the Treatment of Lung Cancer

Yang Bing,Yang Nan,Chen Yaping,Zhu Maomao,Lian Yuanpei,Xiong Zhiwei,Wang Bei,Feng Liang,Jia Xiaobin

Lung cancer is one of the most devastating diseases worldwide, with high incidence and mortality worldwide, and the anticancer potential of traditional Chinese medicine (TCM) has been gradually recognized by the scientific community. Astragali Radix (AR) is commonly used in traditional Chinese medicine in the treatment of lung cancer and has a certain clinical effect, but effective components and targets are still unclear. In the study, we established an integrated strategy for effective-component discovery of AR in the treatment of lung cancer based on a variety of techniques. First, the effective components and potential targets of AR were deciphered by the “component-target-disease” network using network pharmacology, and potential signal pathways on lung cancer were predicted by Gene Ontology (GO) biological function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Then, the therapeutic effects of AR in the treatment of lung cancer were evaluated in vivo using A/J mice, and the potential targets related to autophagy and potential signal pathway were verified by Western blot analysis, immunofluorescence staining, and real-time PCR technology at protein and gene expression level. Finally, metabolism in vitro by rat intestinal flora and cell membrane immobilized chromatography technology were used to screen the effective components of AR in the treatment of lung cancer, and remaining components from the cell immobilized chromatography were collected and analyzed by ultra-performance liquid chromatography–electrospray quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The screening results of the integrated strategy showed that calycosin-7-O-β-D-glucoside, ononin, calycosin, astragaloside IV, astragaloside II, cycloastragenol, and formononetin may be effective components of AR in the treatment of lung cancer, and they may play a role in the treatment of lung cancer through autophagy and p53/AMPK/mTOR signaling pathway. The integrated strategy for effective-component discovery provided a valuable reference mode for finding the pharmacodynamic material basis of complex TCM systems. In addition, the prediction for targets and signal pathways laid a foundation for further study on the mechanism of AR in the treatment of lung cancer.

CAS / MDL: 50-32-8
研究领域: 药理学 · 肿瘤学 · 中医药 · 分子生物学 · 生物信息学
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2024 · IF 3.1

Exploring the gut microbiota mediated biotransformation of Senecio scandens Buch.-Ham.: Insights from metabolite spectrum with UHPLC-Q-Orbitrap HRMS and bioinformatics analysis of gut microbiota metabolites

Jiayue Wang,Feixu Qin,Hongjin Wang,Lu Wang,Caihong Li,Lixin Sun

Senecio scandens Buch.-Ham., a traditional Chinese medicine commonly used clinically, exhibits various pharmacological properties, including anti-inflammatory, anti-tumor, antiviral, and antibacterial activities. However, its water extracts' chemical components and metabolites are inadequately understood, limiting further research. In this study, the chemical components and metabolism processes of Senecio scandens, both in vivo (plasma, feces, urine, and bile) and in vitro (gut microbiota and liver microsomes), were characterized based on ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry. Additionally, metabolites detectable in fecal samples and intestinal microbiota incubated but absent in liver microsomes were identified as characteristic metabolites of intestinal microbiota. The targets of the characteristic metabolites of intestinal microbiota were collected, followed by exploration of potential pathways through KEGG enrichment analysis. As a result, a total of 133 chemical components were preliminarily identified, including 35 organic acids, 21 alkaloids, 19 flavonoids and their glycosides, 17 phenylpropanoids, 10 jacaranda ketones, and 31 other compounds. Notably, 12 of these were potentially novel compounds. In addition, 39 prototype components in rats and 109 metabolites were identified and characterized, including 102 in vivo and 52 metabolites in vitro (51 in rat gut microbiota and 24 in rat liver microsomes). The main metabolic pathways include oxidation, reduction, hydrolysis, methylation, glucuronidation, sulfonation, and acetylation reactions. Furthermore, KEGG enrichment analysis revealed that the characteristic metabolites of intestinal microbiota may be related to the ErbB, FoxO, mTOR, and MAPK signaling pathways, exhibiting anti-inflammatory and anti-tumor effects. In summary, the chemical components and metabolites of Senecio scandens were comprehensively identified using a rapid and accurate method, providing a scientific basis for the in-depth study of the material basis and its clinical application of Senecio scandens .

CAS / MDL: 64-18-6
研究领域: 药理学 · 代谢组学 · 生物信息学 · 中药学 · 化学生物学 · 微生物学
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JOURNAL OF APPLIED TOXICOLOGY · 2020 ·Vol. 41 ·期 8 ·1275-1285 · IF 2.997

The expression profile and bioinformatics analysis of microRNAs in human bronchial epithelial cells treated by beryllium sulfate

Shan Yi,Yan-ping Liu,Xun-ya Li,Xiao-yan Yuan,Ye Wang,Ying Cai,Yuan-di Lei,Lian Huang,Zhao-hui Zhang

Beryllium and its compounds are systemic toxicants that mainly accumulate in the lungs. As a regulator of gene expression, microRNAs (miRNAs) were involved in some lung diseases. This study aimed to analyze the levels of some inflammatory cytokine and the differential expressions of miRNAs in human bronchial epithelial cells (16HBE) induced by beryllium sulfate (BeSO 4 ) and to further explore the biological functions of differentially expressed miRNAs. The profile of miRNAs in 16HBE cells was detected using the high-throughput sequencing between the control groups ( n = 3) and the 150 μmol/L of BeSO 4 -treated groups ( n = 3). Bioinformatics analysis of differentially expressed miRNAs was performed, including the prediction of target genes, Gene Ontology (GO) analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify some damage-related miRNAs. We found that BeSO 4 can increase the levels of some inflammatory cytokine such as interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). And BeSO 4 altered miRNAs expression of 16HBE cells and a total of 179 differentially expressed miRNAs were identified, including 88 upregulated miRNAs and 91 downregulated miRNAs. The target genes predicted by 28 dysregulated miRNAs were mainly involved in the transcription regulation, signal transduction, MAPK, and VEGF signaling pathway. The qRT-PCR verification results were consistent with the sequencing results. miRNA expression profiling in 16HBE cells exposed to BeSO 4 provides new insights into the toxicity mechanism of beryllium exposure.

研究领域: 毒理学 · 分子生物学 · 生物信息学 · 细胞生物学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2021 · IF 5.279

Comprehensive Analysis of Mouse Hippocampal Lysine Acetylome Mediated by Sea Cucumber Peptides Preventing Memory Impairment

Zhiqiang Lu,Xiaomeng Xu,Dongmei Li,Na Sun,Songyi Lin

Memory impairment is becoming a potential health issue with the delicacy of diet and social stress. Sea cucumber peptides (SCP) prevent memory impairment, as previously reported. In this study, further research was performed using hippocampal lysine-acetylome to explore molecular regulation mechanisms. C57BL/6 mice were treated with scopolamine via intraperitoneal injection to simulate memory impairment. To determine the influence of SCP on the total acetylated-protein level of the hippocampus, acetylated-proteomics was performed. SCP increased the acetylation level of histone (H3 and H4). Meanwhile, for non-histones, the differentially acetylated proteins were involved in multiple memory-related pathways, as shown by KEGG enrichment analysis. Additionally, long-term potentiation was confirmed by western blotting. Finally, a combined analysis of proteome and lysine acetylome revealed that SCP contributed to synaptic vesicle cycle regulation and dopamine metabolism. Consequently, our findings revealed that SCP was potentially neuroprotective by regulating post-transcriptional hippocampal protein acetylation.

CAS / MDL: 51-34-3
研究领域: 神经科学 · 蛋白质组学 · 分子生物学 · 药理学
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Chinese Medicine · 2022 ·Vol. 17 ·期 1 ·1-21 · IF 4.546

Asafoetida exerts neuroprotective effect on oxidative stress induced apoptosis through PI3K/Akt/GSK3β/Nrf2/HO-1 pathway

Huang Qianqian,Zhang Chen,Dong Shi,Han Junwen,Qu Sihao,Xie Tianshu,Zhao Haibin,Shi Yuanyuan

Background Alzheimer's Disease (AD) is a serious neurodegenerative disease and there is currently no effective treatment for AD progression. The use of TCM as a potential treatment strategy for AD is an evolving field of investigation. Asafoetida (ASF), an oleo-gum-resin isolated from Ferula assa-foetida root, has been proven to possess antioxidative potential and neuroprotective effects, which is closely associated with the neurological disorders. However, the efficacy and further mechanisms of ASF in AD experimental models are still unclear. Methods A cognitive impairment of mouse model induced by scopolamine was established to determine the neuroprotective effects of ASF in vivo , as shown by behavioral tests, biochemical assays, Nissl staining, TUNEL staining, Immunohistochemistry, western blot and qPCR. Furthermore, the PC12 cells stimulated by H 2 O 2 were applied to explore the underlying mechanisms of ASF-mediated efficacy. Then, the UPLCM analysis and integrated network pharmacology approach was utilized to identified the main constitutes of ASF and the potential target of ASF against AD, respectively. And the main identified targets were validated in vitro by western blot, qPCR and immunofluorescence staining. Results In vivo , ASF treatment significantly ameliorated cognitive impairment induced by scopolamine, as evidenced by improving learning and memory abilities, and reducing neuronal injury, cholinergic system impairment, oxidative stress and apoptosis in the hippocampus of mice. In vitro , our results validated that ASF can dose-dependently attenuated H 2 O 2 -induced pathological oxidative stress in PC12 cells by inhibiting ROS and MDA production, as well as promoting the activities of SOD, CAT, GSH. We also found that ASF can significantly suppressed the apoptosis rate of PC12 cells increased by H 2 O 2 exposure, which was confirmed by flow cytometry analysis. Moreover, treatment with ASF obviously attenuated H 2 O 2 -induced increase in caspase-3 and Bax expression levels, as well as decrease in Bcl-2 protein expression. KEGG enrichment analysis indicated that the PI3K/Akt/GSK3β/Nrf2 /HO-1pathway may be involved in the regulation of cognitive impairment by ASF. The results of western blot, qPCR and immunofluorescence staining of vitro assay proved it. Conclusions Collectively, our work first uncovered the significant neuroprotective effect of ASF in treating AD in vivo . Then, we processed a series of vitro experiments to clarify the biological mechanism action. These data demonstrate that ASF can inhibit oxidative stress induced neuronal apoptosis to foster the prevention of AD both in vivo and in vitro , and it may exert the function of inhibiting AD through PI3K/Akt/GSK3β/Nrf2/HO-1pathway.

CAS / MDL: 6533-68-2
研究领域: 神经科学 · 药理学 · 分子生物学 · 细胞生物学 · 中药学
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Frontiers in Pharmacology · 2022 · IF 5.988

Exploring the potential mechanism of Fritiliariae Irrhosae Bulbus on ischemic stroke based on network pharmacology and experimental validation

Zijie Wang,Anan Jiang,Hongmei Xiao,Xiaofan Yuan,Shaoru Zhang,Xinyue Qin

Objective: To study the potential targets and molecular mechanisms of Fritiliariae Irrhosae Bulbus (FIB) in the treatment of ischemic strokes based on a network pharmacology strategy, with a combination of molecular docking and animal experiments.Methods: The active components and targets of FIB were screened by TCMSP database and TCMIP database, and the related targets of ischemic strokes were screened by GeneCards, OMIM, CTD, and DrugBank, then the intersection targets of the two were taken. The protein interaction network was constructed by STRING, the PPI network diagram was drawn by using Cytoscape software, and the key targets of FIB treatment of ischemic strokes were analyzed by MCODE. The DAVID database was used for GO and KEGG enrichment analysis, and the potential pathway of FIB against ischemic strokes was obtained. Molecular docking was performed by using AutoDock Tools 1.5.6 software. Finally, a mouse model of ischemic stroke was established, and the results of network pharmacology were verified by in vivo experiments. Realtime Polymerase Chain Reaction was used to detect the expression levels of relevant mRNAs in the mouse brain tissue. Western blot was used to detect the expression levels of related proteins in the mouse brain tissue.Results: 13 kinds of active components of FIB were screened, 31 targets were found in the intersection of FIB and ischemic strokes, 10 key targets were obtained by MCODE analysis, 236 biological processes were involved in GO enrichment analysis, and key targets of KEGG enrichment analysis were mainly concentrated in Neuroactive light receptor interaction, Calcium signaling pathway, Cholinergic synapse, Hepatitis B, Apoptosis—multiple specifications, Pathways in cancer and other significantly related pathways. There was good binding activity between the screened main active components and target proteins when molecular docking was performed. Animal experiments showed that the infarct volume of brain tissue in the FIB treatment group was considerably reduced. RT-qPCR and the results of Western Blot showed that FIB could inhibit the expression of active-Caspase3, HSP90AA1, phosphorylated C-JUN, and COX2.Conclusion: Based on network pharmacology, the effect of FIB in the treatment of ischemic strokes was discussed through the multi-component-multi-target-multi-pathway. The therapeutic effect and potential mechanisms of FIB on ischemic strokes were preliminarily explored, which provided a ground work for further researches on the pharmacodynamic material basis, mechanism of action and clinical application.

CAS / MDL: 9004-32-4
研究领域: 药理学 · 神经科学 · 分子生物学 · 生物信息学 · 实验医学
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