BIOORGANIC CHEMISTRY
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2025
·
IF 4.7
Bingjie Wang,Rui Shi,Wanqing Du,Jiaojiao Guo,Nihan He,Yinghong Zhu,Han Yu,Hongyu Lu,Liyuan Zhong,Xingli Li,Wen Zhou,Fei Yang,Xiangling Feng
The recurrence of drug-resistant and expensive treatment drugs are major causes of the low survival rate of multiple myeloma (MM) patients. Exploring a safe, effective, low-cost and novel drug treatment for MM is a promising strategy to relieve the burden of MM patients. In this study, we found that prodigiosin could inhibit MM cell proliferation and induce MM cell apoptosis, however, it had a lesser cytotoxic effect on normal B cells within the IC 50 range of MM cells. In addition, prodigiosin could inhibit the growth of xenograft MM cells in mice. Transcriptomics and targeted amino acid metabolomics confirmed that prodigiosin could regulate amino acid metabolism, and decrease in amino acid utilization by down-regulated aminoacyl tRNA synthetases expression, resulting in slower growth of MM. In conclusion, prodigiosin exerts anticancer effects on MM cells by interfering with the use of amino acids, indicating its potential novel therapeutic application in MM.
研究领域:
肿瘤学
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药理学
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生物化学
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分子生物学
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血液学
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癌症研究
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代谢
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2023
·Vol. 9
·期 7
·e18046
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IF 4
Weijie Zhang,Lei Shi,Wei Zhou,Xin Liu,Yuan Xi,Xinyin Wang,Ya Li,Xia Xu,Youcai Tang
Breast cancer is one of the most common cancers. Oridonin, a traditional Chinese medicine, is believed to inhibit tumor growth, but its particular effects on breast cancer remain unknown. In this study, we examined oridonin's effects on 4T1, MCF-7, and MDAMB-231 cellular activity using CCK8. Scratch assays were used to detect oridonin's effects on cellular migration. Oridonin's effects on the breast cancer cell cycle were studied using flow cytometry, and expression of cell cycle related proteins p53, CDK2, and p21 was detected using Western blot assays. Metabolomics assays were used to detect changes in small molecule metabolites and metabolic pathways in breast cancer cells after treatment with oridonin. Oridonin's effects on breast cancer growth were also studied using xenograft mice. Metabolomics assays were used to detect changes in metabolites and metabolic pathways in xenograft mouse plasma in a control group, model group, and drug administration group. Experimental results showed that oridonin could significantly inhibit breast cancer growth both in vivo and in vitro. Scratch experiments showed that oridonin could inhibit breast cancer cell migration. Oridonin was also able to arrest cells in S phase by affecting several cell cycle-related proteins, including p53, CDK2, and p21. Metabolomic analysis of 4T1 cells identified a total of 33 differential metabolites, including multiple amino acids (such as l-Glutamic acid, l-Asparagine, l-Histidine, l-Valine, and l-Isoleucine). KEGG pathway enrichment analysis showed significant changes in aminoacyl-tRNA biosynthesis, and in multiple amino acid metabolic pathways. Plasma metabolomic analyses of xenograft mice revealed 28 differentially-expressed metabolites between the different animal model groups, including multiple amino acids. KEGG pathway analysis showed significant alterations in multiple amino acid metabolic pathways in oridonin-treated mice. Additionally, changes in the expression of PI3K, AKT and mTOR proteins, as well as in branched amino acids, suggest that oridonin affects the PI3K/AKT/mTOR signaling pathway by inhibiting the biosynthesis of valine, leucine and isoleucine. Taken together, our results suggest that oridonin has strong anti-tumor activity in vitro and in vivo, and has potential as an adjuvant to breast cancer treatment regimens.
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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代谢组学
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DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Yize Liu,Ning Jiang,Si Zuo,Ying Feng,Ran Chen,Yiwei Zhang,Naiwen Zhang,Xiaoyu Sang,Qijun Chen
Hypothesis Trypanosomiasis is one of the main threats to human and animal health in African countries. Trypanosoma brucei can evade the host immune recognition by rapidly altering its variant surface glycoprotein (VSG). The ATP synthase F 1 subunit of the parasite exhibits extremely low similarity to that of its mammalian hosts, hypothetically making it an ideal target for the development of novel therapeutics. Experiments Graphene quantum dots (GQDs) were synthesized, and their adhesion to T. brucei surface and internalization was observed microscopically. The activity of ATP synthase and mitochondrial membrane potential of T. brucei were measured after exposure to GQDs. Proteomics, biolayer interferometry, and molecular dynamic simulations were utilized to evaluate the interaction between GQDs with the target proteins. Findings GQDs specifically adhered to the VSG of T. brucei and were conveyed inside the parasite via the VSG internalization pathway. The GQDs promoted intracellular ROS production, interacted with, and inhibited the activity of the p18 subunit of ATP synthase, disrupted parasite mitochondrial membrane potential. Additionally, the GQDs caused a decrease in aminoacyl – tRNA biosynthesis, and upregulated RNA and protein degradation pathways. The findings of this study offer a novel avenue for the target-oriented discovery of anti-trypanosome drugs.
研究领域:
寄生虫学
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纳米技术
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分子生物学
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药物发现
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2023
·
IF 13.6
Liwen Qiang,Nan Zhao,Kaizhen Liao,Xichao Sun,Qiang Wang,Hangbiao Jin
Engineered nanoparticles (ENPs) can resist heavy metal toxicity in plants, but their coexposure still exhibits toxicity to plants compared to plants without exposure to ENPs and heavy metals. There have been few studies on the toxic mechanism of nano TiO 2 -heavy metal coexposure and the effect mechanism of nano TiO 2 in plants. Thus, transcriptomics and metabolomics were used to study the toxic mechanism of rutile nano TiO 2 or TiO 2 -Cd (rutile nano TiO 2 and CdCl 2 mixture) on rice ( Oryza sativa L.). After 40 days of exposure, the plant height and root dry weight of rice were significantly decreased in the nano TiO 2 -Cd group compared to the blank group (nano TiO 2 and CdCl 2 free). After Cd treatment, 423 differentially expressed genes (DEGs) and 16 differential metabolites were identified. Nano TiO 2 exposure induced significant regulation of 299 DEGs and 6 metabolites. After nano TiO 2 -Cd coexposure, 1660 DEGs and 181 differential metabolites were identified. Notably, the EDGs (e.g., chalcone isomerase and hydroxycinnamoyl transferase) and differential metabolites (e.g., chrysin and galangin) demonstrated the disruption of flavonoid biosynthesis in Cd-treated rice. After rice was exposed to nano TiO 2 , the DEGs were related to ribosome, whereas the differential metabolites were associated with pyruvate metabolism and valine, leucine , and isoleucine biosynthesis. Furthermore, 14 DEGs (e.g., asparaginyl-tRNA synthetase and methionyl-tRNA formyltransferase) involved in aminoacyl-tRNA biosynthetic pathways were significantly upregulated in rice treated with nano TiO 2 -Cd, in line with the changes in related metabolites (e.g., L -asparagine and 10-formyltetrahydrofolate). Our results show that it is necessary to pay close attention to the toxicity of nano TiO 2 -Cd coexposure in paddy ecosystems and use ENPs with caution to combat the phytotoxicity of heavy metals.
研究领域:
植物科学
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毒理学
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分子生物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-13
·
IF 16.6
Chang Tiantian,Ding Weichao,Yan Shirui,Wang Yun,Zhang Haoling,Zhang Yu,Ping Zhi,Zhang Huiming,Huang Yijian,Zhang Jiahui,Wang Dan,Zhang Wenwei,Xu Xun,Shen Yue,Fu Xian
Synthetic auxotrophy in which cell viability depends on the presence of an unnatural amino acid (unAA) provides a powerful strategy to restrict unwanted propagation of genetically modified organisms (GMOs) in open environments and potentially prevent industrial espionage. Here, we describe a generic approach for robust biocontainment of budding yeast dependent on unAA. By understanding escape mechanisms, we specifically optimize our strategies by introducing designed “immunity” to the generation of amber-suppressor tRNAs and developing the transcriptional- and translational-based biocontainment switch. We further develop a fitness-oriented screening method to easily obtain multiplex safeguard strains that exhibit robust growth and undetectable escape frequency (<~10 −9 ) on solid media for 14 days. Finally, we show that employing our multiplex safeguard system could restrict the proliferation of strains of interest in a real fermentation scenario, highlighting the great potential of our yeast biocontainment strategy to protect the industrial proprietary strains.
研究领域:
生物技术
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分子生物学
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基因工程
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微生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Linlin Wang,Lilong Wang,Cui Cao,Jun Zhao,Chen Song,Zhijie Bao,Chunhong Yan,Shuang Song
Excessive protein consumption (EPC) could increase the gastrointestinal burden and impair gut motility. The present study was designed to explore the improvement of chitosan (CTS) and chitosan oligosaccharide (COS) on colonic motility and serum metabolites in rats after EPC. The results of in vivo experiments fully proved that CTS and COS could improve gut motility and reverse the serum metabolites in rats as indicated by LC-MS/MS analysis, and the COS group even showed a better effect than the CTS group. Furthermore, short-chain fatty acids (SCFAs), which could promote gut motility, were also increased to alleviate EPC-induced constipation after supplementation with CTS or COS. In addition, CTS and COS could decrease the concentration of ammonia in serum and down-regulate the levels of H 2 S and indole. In summary, the present study revealed that CTS and COS could produce SCFAs, improve the colonic motility in rats, reverse the levels of valine , adenosine, cysteine, 1-methyladenosine, indole, and uracil , and enhance aminoacyl-tRNA biosynthesis and valine, leucine and isoleucine degradation. The present study provides novel insights into the potential roles of CTS and COS in alleviating the adverse effects of EPC.
研究领域:
营养学
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胃肠病学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
PeerJ
·
2024
·
IF 2.3
Mengxiang Du,Shengwei Huang,Zihan Huang,Lijuan Qian,Yang Gui,Jing Hu,Yujun Sun
Although Morchella esculenta (L.) Pers. is an edible and nutritious mushroom with significant selenium (Se)-enriched potential, its biological response to selenium stimuli remains unclear. This study explored the effect of selenium on mushroom growth and the global gene expression profiles of M. esculenta . While 5 µg mL −1 selenite treatment slightly promoted mycelia growth and mushroom yield, 10 µg mL −1 significantly inhibited growth. Based on comparative transcriptome analysis, samples treated with 5 µg mL −1 and 10 µg mL −1 of Se contained 16,061 (452 upregulated and 15,609 downregulated) and 14,155 differentially expressed genes (DEGs; 800 upregulated and 13,355 downregulated), respectively. Moreover, DEGs were mainly enriched in the cell cycle, meiosis, aminoacyl-tRNA biosynthesis, spliceosome, protein processing in endoplasmic reticulum pathway, and mRNA surveillance pathway in both selenium-treated groups. Among these, MFS substrate transporter and aspartate aminotransferase genes potentially involved in Se metabolism and those linked to redox homeostasis were significantly upregulated, while genes involved in isoflavone biosynthesis and flavonoid metabolism were significantly downregulated. Gene expression levels increased alongside selenite treatment concentration, suggesting that high Se concentrations promoted M. esculenta detoxification. These results can be used to thoroughly explain the potential detoxification and Se enrichment processes in M. esculenta and edible fungi.
研究领域:
真菌学
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转录组学
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分子生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
Aging-US
·
2020
·
IF 4.831
Lan Xiang,Qiaobei Wu,Hiroyuki Osada,Minoru Yoshida,Wensheng Pan,Jianhua Qi
In this study, mice with type 2 diabetes mellitus (T2DM) induced by high-fat diet were used to investigate the antidiabetic effect and mechanism of action of peanut skin extract (PSE). Results revealed that the fasting blood glucose, body weight, and food intake of mice with T2DM significantly decreased after they were given PSE. The effects of 80 mg/kg PSE were similar to those of 140 mg/kg metformin (MET). The glucose tolerance and insulin sensitivity of the mice also improved. The composition of intestinal microflora in the mice significantly changed after PSE administration. In particular, no Actinobacteria was detected in the PSE-treated group, and the ratio of Firmicutes to Bacteroidetes was remarkably reduced. PSE also increased the abundance of gut microbiota involved in fatty acid biosynthesis, lipid biosynthesis, and sucrose metabolism. The abundance of gut microbiota related to aminoacyl-tRNA biosynthesis also decreased. Lipopolysaccharide, interleukin (IL)-6, IL-1β and tumor necrosis factor-α in the blood, liver and adipose tissue were reduced by PSE. Similarly, the mRNA expression levels of IkappaB kinase and nuclear factor kappaB in the hypothalamus were reduced by PSE. These results suggested that PSE and MET elicited significant antidiabetic effects by maintaining gut microbiota and inhibiting inflammation.
研究领域:
药理学
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糖尿病研究
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微生物学
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营养学
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免疫学
✓ 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）