Journal of Oncology
·
2022
·
IF 4.501
Junying Xu,Xuejing Yang,Jiadong Pan,Honghong Fan,Jie Mei,Dong Hua
Objective. To investigate the regulatory effect of ZEB1 on PD-L1 expression and the pharmacodynamic effects of Biochanin A on the malignant biological behaviors of colorectal cancer (CRC). Methods. The correlation between epithelial-mesenchymal transition (EMT) score and features of the tumor microenvironment (TME) was investigated using the Cancer Genome Atlas (TCGA) dataset. The correlation between ZEB1 and PD-L1 expression was validated using immunohistochemistry (IHC) staining, and the regulatory effect of ZEB1 on PD-L1 expression was explored by in vitro assays. Moreover, the pharmacodynamic effects of Biochanin A on ZEB1 and PD-L1 expression, as well as malignant biological behaviors of CRC cells, were evaluated by in vitro and in vivo assays. Results. EMT score was positively correlated with a majority of immunostimulators, immune checkpoints, activities of antitumor immunity cycles, and infiltration levels of most immune cells in the TCGA dataset. In addition, ZEB1 was correlated with and positively regulated PD-L1 expression in CRC. Besides, Biochanin A, an inhibitor for the ZEB1/PD-L1 axis, notably inhibited ZEB1-mediated aggressiveness and PD-L1 expression of CRC cells. Moreover, Biochanin A also exerted a tumor-inhibitory role in vivo in the CRC mouse model. Conclusion. Overall, we found that ZEB1 is a main regulator of PD-L1 expression in CRC. In addition, we also identified Biochanin A as a novel inhibitor for the ZEB1/PD-L1 axis, which could inhibit tumor progression and immune escape.
研究领域:
肿瘤学
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分子生物学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Peijun Sun,Huixian Chen,Xiaoyu Fan,Jiayi Wang,Lujie Lu,Guangchao Yang,Jining Liu,Weifeng Yao,Feng Ding,Jie Ding,Jianmei Liu,Tulin Lu,Lihong Chen
Ethnopharmacological relevance Licorice is widely used clinically as one of the most famous traditional Chinese herbs. Its herb roasted with honey is called honey-processed licorice (HPL). Modern studies have shown that HPL has a stronger cardioprotective ability compared to raw licorice (RL), however the material basis and mechanism of action of the potential cardioprotection have not been fully elucidated. Aim of the study To screen and validate the material basis of cardioprotection exerted by HPL and to preliminarily predict the potential mechanism of action. Materials and methods UPLC-QTOF-MS/MS was used to analyze HPL samples with different processing levels, and differential compounds were screened out through principal component analysis. Network pharmacology and molecular docking were applied to explore the association between differential compounds and doxorubicin cardiomyopathy and their mechanisms of action were predicted. An in vitro model was established to verify the cardioprotective effects of differential compounds. Results Six differential compounds were screened as key components of HPL for potential cardioprotection. Based on network pharmacology, 113 potential important targets for the treatment of Dox-induced cardiotoxicity were screened. KEGG enrichment analysis predicted that the PI3K-Akt pathway was closely related to the mechanism of action of active ingredients. Molecular docking results showed that the six differential compounds all had good binding activity with Nrf2 protein. In addition, in vitro experiments had shown that five of the active ingredients (liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, and licochalcone A) can significantly increase Dox-induced H9c2 cell viability, SOD activity, and mitochondrial membrane potential, significantly reduces MDA levels and inhibits ROS generation. Conclusion Liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin and licochalcone A are key components of HPL with potential cardioprotective capabilities. Five active ingredients can alleviate Dox-induced cardiotoxicity by inhibiting oxidative stress and mitochondrial damage.
研究领域:
药理学
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中药学
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心脏病学
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Chengcheng Xiao,Peng Wang,Yayun Wang,Jiaxi Zhu,Hai Zhu,Xin Li,Renhe Wang
Ethnopharmacological relevance Acute kidney injury (AKI) is a growing worldwide health concern. Danggui Shaoyao San (DGSYS) was an frequently-used representative prescription to "promote blood and water and harmonize the body" in traditional Chinese medicine, and its underlying mechanism against AKI remains to be elucidated. Aim of the study To investigate the protective effect and potential molecular mechanism of DGSYS in alleviating AKI by network pharmacology and experiment validation. Materials and methods DGSYS was analyzed and separated by UHPLC. Network pharmacology, molecular docking and molecular dynamics simulation were used to screen the active ingredient-target pathway of DGSYS for AKI treatment. Meanwhile, the predictions were experimentally validated both in vivo and in vitro . Results 30 bioactive compounds and 821 non-repetitive targets were screened for DGSYS, and 292 potential DGSYS-AKI intersection targets were identified. According to the protein–protein interaction results and GO and KEGG analyses, we found that apoptosis mediated by SRC pathway exerted a vital role in DGSYS against AKI. In vivo experiments indicated that DGSYS mitigated I/R-induced kidney injury by suppressing SRC signaling pathway. Molecular docking and molecular dynamics simulation revealed that paeoniflorin (PF) have good binding affinity to SRC. Subsequently, in vitro experiments suggested that PF was the key bioactive compound against AKI from DGSYS by inhibiting SRC/ERK1/2 signaling pathway. Conclusion We exhibited the promising anti-AKI mechanism of DGSYS, and our findings also opened up an avenue for future basic experimental validation, indicating a novel research direction.
研究领域:
药理学
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网络生物学
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计算生物学
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中医药学
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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
PLoS One
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2013
·Vol. 8
·期 9
·e76007
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IF 3.73
Xiang Li,Yuanyuan Liu,Xueling Hou,Hongjun Peng,Li Zhang,Qingbo Jiang,Mei Shi,Yun Ji,Yuyue Wang,Weifeng Shi
Enterovirus 71 (EV71) is an etiology for a number of diseases in humans. Traditional Chinese herbs have been reported to be effective for treating EV71 infection. However, there is no report about the antiviral effects of CHA against EV71. In this study, plaque reduction assay demonstrated that the inhibitory concentration 50% (IC50) of CHA on EV71 replication is 6.3 µg/ml. When both CHA (20 µg/ml) and EV71 were added, or added post-infection at different time points, CHA was able to effectively inhibit EV71 replication between 0 and 10 h. In addition, CHA inhibited EV71 2A transcription and translation in EV71-infected RD cells, but did not affect VP1, 3C, and 3D expression. Furthermore, CHA inhibited secretions of IL-6, TNF-α, IFN-γ and MCP-1 in EV71-infected RD cells. Altogether, these results revealed that CHA may have antiviral properties for treating EV71 infection.
研究领域:
病毒学
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药理学
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中医药
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DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2019
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IF 2.931
Xianmei Piao,Zhongrui Liu,Yangyang Li,Dahong Yao,Liwen Sun,Baihui Wang,Yan Ma,Libo Wang,Yan Zhang
Bisphenol A (BPA) as a chemical raw material, is widely used in the manufacturing process of daily necessities. It was reported that BPA could induce oxidative stress , and catalase (CAT) can protect the body from oxidative stress. In this paper, the effect of BPA on CAT was carried out in vitro and in vivo. Firstly, we studied the effects of BPA on oxidative stress, cell viability and CAT activity in human hepatocytes, and the results of vitro experiments show that the survival rate of hepatocytes significant decreased along with the increase of BPA concentration. And when the BPA concentration was 100 μM, the hepatocyte survival decreased by 13.2%, ROS levels in the cells increased by 85%. However, the activity of intracellular CAT increased with the increasing concentration of BPA in 24 h. The results of vivo experiments showed that the activity of CAT in the high-dose group decreased by 29.1% compared with the control group. The long-term effects of BPA on rats reduced the CAT activity in liver, which reduced the resistance to oxidative stress. Meanwhile, the interaction mechanism between BPA and CAT at the molecule level was performed via multiple spectra methods and molecular docking, and the results illustrated that the structural change of CAT is mainly due to the strong combination of BPA with the residues of Trp185. In addition, the interaction mechanism between BPA and CAT were hydrophobic and electrostatic effect. This study provided experimental evidence for better understanding the toxicity of BPA.
研究领域:
毒理学
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细胞生物学
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生物化学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2019
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IF 8.355
Yunfeng Hu,Shi Wu,Yong He,Liehua Deng
A redox prodrug consisting of camptothecin-conjugating PEG through the diselenide bond was synthesized, and the resultant amphiphilic prodrug was then used to load the curcumin to form the co-delivery system for the synergetic B16 melanoma cells inhibition. The co-delivery system showed a good response to glutataione, and the prodrug could be degraded and the two loaded drugs were then released. Both camptothecin and curcumin could induce the obvious cytotoxicity to B16 melanoma cells. Particularly, the co-delivery strategy showed a synergetic inhibition effect to B16 melanoma cells through an in vitro assay. In vivo assay also showed that the co-delivery system could inhibit B16 tumor growth and showed much better inhibition effect than that of only camptothecin or curcumin used. Moreover, as an injectable drug delivery system, the biocompatibility including the blood compatibility of the co-delivery system was confirmed, suggesting that the redox co-delivery system have a potential application in B16 tumor therapy.
研究领域:
药学
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肿瘤学
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药物递送系统
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生物医学工程
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产品关联
DOI
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Hui Li,Jian Tian,Anqing Wu,Jiamin Wang,Cuicui Ge,Ziling Sun
Self-assembled nanoparticles of the natural polymer, silk fibroin (SF), are a very promising candidate in drug delivery due to their biocompatible and biodegradable properties. In this study, SF nanoparticles loaded with 5-fluorouracil (5-FU) and curcumin with size 217±0.4 nm and with a loading efficacy of 45% and 15% for 5-FU and curcumin, respectively, were prepared. The in vitro release effect of 5-FU and curcumin from nanoparticles was evaluated as ~100% and ~5%, respectively. It has been revealed that the application of such a nanodrug can increase the level of reactive oxygen species, which in turn induces apoptosis of cancer cells in vitro. Animal studies have shown that tumors could be noticeably reduced after being injected with the drug-entrapped nanoparticles. More apoptotic cells were found after 7 days of treatment with SF nanoparticles by a hematoxylin–eosin staining assay. These results demonstrate the future potential of nanoparticle-loaded binary drugs in the treatment of breast cancer.
研究领域:
纳米技术
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药理学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Cancer Genetics
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2023
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IF 1.9
Shuoyi Zhang,Ming Zhong,Hongbo Zhu,Qinghua You,Hao Yuan,Yongping Li
ABSTRACT We investigated the effect of stem cell marker dopamine receptor D2 (DRD2) on the proliferation of hormone-receptor-negative breast cancer cells. High-throughput DNA methylation sequencing on an 850K chip was used to pre-screen breast cancer tissues with significant methylation differences. The expression of DRD2 in breast cancer and normal breast tissues, and clinical risk factors, were detected by pyrophosphoric acid validation and immunohistochemistry. In vitro and in vivo experiments verified the possible molecular signaling pathways. DRD2 promoter region was hypomethylated in hormone-receptor-negative breast cancer or with high-risk factors compared to the normal tissues. The proliferation of breast cancer cells was enhanced after DRD2 was upregulated and decreased after DRD2 was downregulated. In vivo experiments found that tumor growth and the expression of antigen KI-67 (Ki67) and the cluster of differentiation 31 (CD31) were improved by the overexpression of DRD2 and inhibited by the down expression of DRD2. In vivo and in vitro experiments demonstrated the phosphorylation of filamin A and extracellular signal-regulated kinase (FLNA-ERK) was influenced by the expression of DRD2, suggesting DRD2 plays a role in the FLNA-ERK signaling pathway. Methylation inhibitors (5-aza-2-deoxycytidine, 5-azadc) partially reversed the inhibitory effect of DRD2 down expression on cell proliferation, migration, and tumor growth in animal models, indicating that inhibition of DRD2 methylation promotes cancer development. This study demonstrated the DRD2 promoter region is hypomethylated in hormone-receptor-negative breast cancer or with high-risk factors. The methylation status of the DRD2 promoter and FLNA-ERK signaling pathway and the DRD2 expression in breast cancer treatment need to be considered.
研究领域:
肿瘤学
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分子生物学
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癌症遗传学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2023
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IF 5.6
Feng Zhao,Xiaojuan Wang,Hui Liu,Jiang Qian
White tea is a kind of tea abundant in oligopeptides. The study aims to reveal the potential association between white tea oligopeptides and anti-inflammatory ability. Crude oligopeptide extracts of two subtype white tea (named BaiMudan and ShouMei) were prepared by removing known active substances including pigments, polyphenols, caffeine, polysaccharides, and free amino acids. Four abundant oligopeptides (LCAY, LLLSKKL, EVFAG, and ECDSCG) were identified through high-resolution mass spectrometry sequencing, and synthesized for anti-inflammation evaluation. In vitro experiments showed, expect there was no effect of EVFAG on TNF-α, the rests oligopeptides were all good at inhibit NO, IL-6, and TNF-α. In vivo experiments indicated a notable decrease in neutrophils of zebrafish yolk sac. Specifically, performance of LCAY was particularly outstanding, with its anti-inflammatory effect at 250 μg·mL −1 could exceed 100 μM dexamethasone. The prominent significance of this study is that it confirms white tea oligopeptides have a good anti-inflammatory activity.
研究领域:
药理学
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生物化学
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分子生物学
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炎症研究
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产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2024
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IF 10
Chengyun Hu,Xue Yuan,Ronghua Zhao,Biao Hong,Chuang Chen,Qingjun Zhu,Yanmin Zheng,Jinming Hu,Yue Yuan,Zhengyan Wu,Jia Zhang,Chaoliang Tang
Prussian blue (PB) nanozymes are demonstrated as effective therapeutics for ulcerative colitis (UC), yet an unmet practical challenge remains in the scalable production of these nanozymes and uncertainty over their efficacy. With a novel approach, a series of porous manganese-iron PB (MnPB) colloids, which are shown to be efficient scavengers for reactive oxygen species (ROS) including hydroxyl radical, superoxide anion, and hydrogen peroxide, are prepared. In vitro cellular experiments confirm the capability of the nanozyme to protect cells from ROS attack. In vivo, the administration of MnPB nanozyme through gavage at a dosage of 10 mg kg −1 per day for three doses in total potently ameliorates the pathological symptoms of acute UC in a murine model, resulting in mitigated inflammatory responses and improved viability rate. Significantly, the nanozyme produced at a large scale can be achieved at an unprecedented yield weighting ≈11 g per batch of reaction, demonstrating comparable anti-ROS activities and treatment efficacy to its small-scale counterpart. This work represents the first demonstration of the scale-up preparation of PB analog nanozymes for UC without compromising treatment efficacy, laying the foundation for further testing of these nanozymes on larger animals and promising clinical translation.
研究领域:
纳米技术
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药学
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生物医学工程
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医学
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产品关联
DOI
PubMed
高影响因子
Metabolites
·
2024
·Vol. 14
·期 4
·224
·
IF 3.4
Jianing Ren,Jing Dai,Yue Chen,Zhenzhen Wang,Ruyi Sha,Jianwei Mao,Yangchen Mao
Rice (Oryza sativaL.) is one of the primary sources of energy and nutrients needed by the body, and rice resistant starch (RRS) has been found to have hypoglycemic effects. However, its biological activity and specific mechanisms still need to be further elucidated. In the present study, 52 RRS differential metabolites were obtained from mouse liver, rat serum, canine feces, and human urine, and 246 potential targets were identified through a literature review and database analysis. A total of 151 common targets were identified by intersecting them with the targets of type 2 diabetes mellitus (T2DM). After network pharmacology analysis, 11 core metabolites were identified, including linolenic acid, chenodeoxycholic acid, ursodeoxycholic acid, deoxycholic acid, lithocholic acid, lithocholylglycine, glycoursodeoxycholic acid, phenylalanine, norepinephrine, cholic acid, and L-glutamic acid, and 16 core targets were identified, including MAPK3, MAPK1, EGFR, ESR1, PRKCA, FYN, LCK, DLG4, ITGB1, IL6, PTPN11, RARA, NR3C1, PTPN6, PPARA, and ITGAV. The core pathways included the neuroactive ligand–receptor interaction, cancer, and arachidonic acid metabolism pathways. The molecular docking results showed that bile acids such as glycoursodeoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, lithocholic acid, deoxycholic acid, and cholic acid exhibited strong docking effects with EGFR, ITGAV, ITGB1, MAPK3, NR3C1, α-glucosidase, and α-amylase. In vitro hypoglycemic experiments further suggested that bile acids showed significant inhibitory effects on α-glucosidase and α-amylase, with CDCA and UDCA having the most prominent inhibitory effect. In summary, this study reveals a possible hypoglycemic pathway of RRS metabolites and provides new research perspectives to further explore the therapeutic mechanism of bile acids in T2DM.
研究领域:
药理学
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生物化学
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分子生物学
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糖尿病研究
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Peptide Science
·
2024
·
IF 1.5
Xinjian Bi,Yu Gao,Shiyu Wen,Ziyi Chen,Tong Wu,Jiaqi Wang,Yanmei Hou,Xiaoyu Peng,Wei Li,Lina Pan,Li Wen
Bioactive peptides (BAPs) have attracted considerable interest in scientific research due to their heterogeneity in sequence and structure, which underpins various biological functionalities. In this context, goat casein, an abundant by-product of the dairy industry, emerges as a valuable source of BAPs. The present study undertook a meticulous evaluation of the bioactive potentials of goat casein-derived peptides through an integrated approach combining computational simulations, high-throughput screening, and molecular docking techniques. The initial phase involved the enzymatic digestion of goat milk casein using trypsin, followed by the identification of peptides via liquid chromatography–tandem mass spectrometry (LC–MS/MS), uncovering a total of 597 peptides. Subsequent prioritization using the PeptideRanker algorithm identified 70 peptides exhibiting potential bioactivity, as denoted by scores above 0.8. Advanced screening employing the BIOPEP database and the AutoDock and CAMPR4 tools facilitated the elucidation of 16 antioxidant, 59 hypotensive, 63 hypoglycemic, 70 hypolipidemic, and 25 antimicrobial peptides. Molecular docking studies further elucidated the spontaneous nature of the interactions between the peptides and their respective receptors, predominantly mediated by hydrogen bonding and hydrophobic interactions. Four peptides specifying all activities simultaneously were synthesized, and their activities were verified by in vitro experiments. These results not only highlight an effective strategy for the high-throughput screening of goat casein-derived peptides but also underscore the potential of utilizing casein as a viable source of functional food ingredients. This study thereby contributes significantly to the expanding field of functional food research, suggesting a sustainable approach to explore the potential of dairy by-products. Graphical
研究领域:
食品科学
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生物化学
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计算生物学
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药学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）