Frontiers in Pharmacology
·
2021
·
IF 5.811
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.
研究领域:
药理学
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肿瘤学
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中医药
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分子生物学
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生物信息学
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Li Wang,Kang Wei,Yi Pan,Yang Wei,Zhengwu Wang,Lurong Xu,Yuanfeng Wang,Xinlin Wei
The hazardous effects of residues from organophosphorus pesticides (OPPs) on human health have prompted researchers to look for innovative adsorbents and detecting techniques. Herein, a simple and economical material Fe 3 O 4 @PCN-224 was effectively produced as a desirable adsorbent for OPPs residues adsorption by integrating magnetic polydopamine (PDA) with the zirconium-based metal-organic framework (PCN-224). Modification of magnetic cores with PCN-224 allowed a dramatic increase in surface area and porosity to enhance pesticide adsorption. Moreover, the adsorption mechanisms inferred that π-π interactions, covalent bonds, and hydrogen bonds may promote the beneficial adsorption of OPPs by Fe 3 O 4 @PCN-224. Finally, the Fe 3 O 4 @PCN-224-based HPLC method exhibited with low detection limits (0.014–0.051 μg/L), good precision (1.70 % – 3.49 %), wide linearity (1–100 μg/L, R 2 ≥ 0.9936), satisfactory recoveries (86.16 % – 106.45 %), and high enrichment factors (92–101), demonstrating its significant potential for efficient extraction, enrichment, and analysis of OPPs in complex matrix samples.
研究领域:
环境科学
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分析化学
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产品关联
DOI
PubMed
高影响因子
INFLAMMATION RESEARCH
·
2025
·Vol. 74
·期 1
·1-20
·
IF 5.4
Song Chao,Shen Baoxin,Chen Chaoqi,Yang Lei,Zhang Chi,Liu Fei,Chen Feng,Wu Xiaofei
Background Osteoarthritis (OA) is a common chronic degenerative joint disease in orthopedics, and ferroptosis is a newly identified mode of cell death present in OA. Inhibition of inflammatory cytokine expression and modulation of chondrocyte ferroptosis related pathways may be novel strategies for the treatment of OA. The purpose of this work was to uncover prospective biomarkers and molecular processes of ferroptosis in OA, as well as to better understand the molecular mechanisms of ferroptosis in OA treated with resveratrol. Material and methods We obtained OA gene expression profiles from the Gene Expression Omnibus (GEO) database. OA-expressed ferroptosis-related genes were identified using Genecards data, differential gene analysis, and weighted gene co-expression network analysis. Enrichment analysis was utilized to identify signaling pathways and molecular mechanisms linked with ferroptosis in OA, while immune infiltration analysis indicated immune cell infiltration in OA. The action targets of resveratrol were taken from the TCM database to determine the therapeutic targets of resveratrol for the treatment of OA. To validate the molecular process, molecular docking was performed using the therapeutic targets' enrichment analysis. Finally, in vitro investigations confirmed the molecular mechanism of ferroptosis in resveratrol-treated OA. Results Bioinformatic analysis identified 462 OA ferroptosis gene sets, with GPX4, TFRC, SLC7A11, EGFR, and IL1B serving as significant hub genes. Enrichment analysis revealed that ferroptosis was also linked to animal mitophagy, the FoxO signaling pathway, the Toll-like receptor signaling pathway, the PI3K-Akt signaling pathway, inflammation, immune response activation, and cellular autophagy. The immune infiltration data revealed that T_cells_CD4_memory_resting, T_cells_CD4_memory_activated, NK_cells_activated, and Mast_cells_activated were considerably infiltrated in OA. Resveratrol ameliorated OA via modulating autophagy and ferroptosis via GPX4, TFRC, SLC7A11, EGFR, and IL1B, according to a mechanistic study. Conclusion We discovered the mechanism of GPX4, TFRC, SLC7A11, and EGFR, IL1B ferroptosis-related genes in OA, and preliminary evidence suggests that resveratrol improves OA by regulating ferroptosis and immunological processes, which may give a new route for OA treatment.
研究领域:
医学
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生物信息学
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DOI
PubMed
高影响因子
Future Medicinal Chemistry
·
2021
·Vol. 13
·期 15
·
IF 3.808
Yunong Li,Jingbo Yang,Yan Zhang,Qingkang Meng,Andreas Bender,Xiujie Chen
Background: A comprehensive approach to drug repositioning will be required to overcome translational hurdles and identify more neuroprotective drugs. Results & methods: Gene Set Enrichment Analysis was applied to identify related pathways and enriched genes. Candidate genes were optimized using ToppGene, ToppGenet and pBRIT. From the perspective of the local structures, gene–domain–substructure–drug relationships were constructed. Using the MCODE algorithm and K-means clustering, 31 functional subnetworks were obtained, and 252 drugs with proposed neuroprotective function were identified. Using computational analysis, 72 substructures with different scores were found to correspond to neuroprotective functions. The protective effects of benidipine and barnidipine were confirmed in vitro. Conclusion: The authors' research has great potential to discover more neuroprotective drugs and obtain more information regarding mechanisms of action and functional substructures.
研究领域:
生物信息学
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药物研发
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神经科学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Ping Zhang,LuLu Ran,Furong Yang,Cancan Yang,Xiaojing Huang,Xiaojiang Ke,Zhifeng Xu,Lin He
This study systemically investigated the enantioselective bioaccumulation and degradation of etoxazole (ETZ) in earthworms along with the transcriptome and oxidative stress responses to ETZ enantiomer exposure. Based on the M-shaped bioaccumulation trends for ETZ enantiomers, R-ETZ was found to be preferentially bioaccumulated in earthworms. Sublethal toxicity analysis showed that S-ETZ induced greater changes in protein content, malondialdehyde content, detoxifying metabolic enzyme activity, and oxidative stress in earthworms, compared to those induced by R-ETZ. Integrated biomarker response analysis suggested that S-ETZ induced higher sublethal toxicity in earthworms than R-ETZ. Finally, transcriptomic analysis indicated that 845 and 314 genes were differentially expressed after R-ETZ and S-ETZ exposure, respectively, when compared to the nonexposed control group. Enrichment analysis indicated that these differentially expressed genes were primarily enriched in the digestion and absorption of proteins, lysosome, peroxisome, and peroxisome proliferator-activated receptor signaling pathways. These results suggest that earthworms exhibit distinct enantioselective responses to S-ETZ and R-ETZ. This study elucidates the enantioselective bioaccumulation, degradation, transcriptome, and oxidative stress characteristics of ETZ enantiomers in earthworms at the enantiomer level, offering a theoretical foundation to improve the risk assessment of ETZ in the soil–earthworm microsomes.
研究领域:
环境科学
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毒理学
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分子生物学
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生态毒理学
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基因组学
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DOI
PubMed
高影响因子
RSC Advances
·
2019
·Vol. 9
·期 70
·41088-41098
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IF 3.049
Danqi Li,Da Liu,Dandan Yue,Pinyi Gao,Cheng Du,Xuegui Liu,Lixin Zhang
Breast cancer remains the most commonly diagnosed malignancy among women, which is frequently associated with adverse side-effects and high metastasis. Bupleurum chinense DC. has been empirically and extensively used as the core prescription for more than half of Chinese formulations for the adjuvant therapy of breast cancer, and its biological activity against breast cancer has been proven by both in vitro and in vivo experiments. Saikosaponin compounds are the characteristic constituent of B. chinense, which exhibit significant cytotoxicity toward several cancer cells. However, the specific mechanisms of these compounds in the treatment of breast cancer have not been comprehensively understood. Therefore, we aimed to determine more potentially therapeutic targets and investigate the biological mechanisms of B. chinense. In the present study, we adopted network pharmacology and bioinformatics analysis to facilitate this requirement. Consequently, the network analysis revealed that saikosaponin-f (39), saikosaponin-d (14), saikosaponin-c (26), saikosaponin-h (54), saikosaponin-g (41), 3′′,6′′-O-diacetylsaikosaponin-d (20), 11α-methoxy-saikosaponin-f (40), and 6′′-O-acetylsaikosaponin-b1 (48) might play important roles in the treatment of breast cancer. In addition, the apoptosis regulator Bcl-2 (BCL-2), C-X-C chemokine receptor type 4 (CXCR4), probable ATP-dependent RNA helicase DDX5 (DDX5), protein kinase C alpha (PRKCA), and proto-oncogene tyrosine-protein kinase Src (SRC) were the potential therapeutic targets that exhibited intense interactions. Mechanistically, a gene enrichment analysis revealed that the action of B. chinense against breast cancer was achieved by the regulation of several biological signaling pathways, such as pathways in cancer, PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, microRNAs in cancer, etc. More importantly, we verified that the predictions involving saikosaponin-d by the cytotoxicity assay, apoptosis analysis, and RNA sequencing methods were partly consistent with those obtained from the network pharmacology prediction.
研究领域:
药理学
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生物信息学
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癌症研究
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分子生物学
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中药学
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产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2022
·
IF 4.631
Meng Zhang,Yi Liu,Jing Chen,Lei Chen,Li Zhang,Xianguo Chen,Zongyao Hao,Chaozhao Liang
Background Chronic nonbacterial prostatitis (CNP) has a high incidence, low cure rate, and unclear pathogenesis. Here, we aimed to systematically identify effective diagnostic and therapeutic targets for CNP.Methods Prostate tissues were obtained from established mouse models and negative controls and were used for mRNA array sequencing and immunohistochemistry (IHC) staining. Predominant pathways were identified based on pathway enrichment analysis and pharmaceutical experiments. We also investigated the functional role of CXCL12 on CP, a critical factor belonging to the predominant chemotaxis pathway, and employed IHC staining to explore the influence of the CXCL12/CXCR4 axis on the activation of the NF-κB, AKT, and STAT3 signaling pathways. Serum samples derived from both CNP cases and healthy controls were used to determine the secretion level of CXCL12.Results By employing mRNA array sequencing and immunohistochemistry, we found that CXCR4, CXCL12, CD44, and OFLM4 were highly expressed in the infiltrated inflammatory T cells of the prostate tissues generated from CNP mice, while they were rarely expressed on the epithelial cells. Based on the pathway enrichment results, we applied pathway inhibitors to suppress the activity of these classic pathways. We found that targeting the CXCL12/CXCR4 axis with its specific antagonist AMD3100 remarkably alleviated inflammatory infiltration of the prostate in CNP models. Similar results were obtained when we replaced AMD3100 with adenovirus-associated virus (AAV)-shCxcl12. To clarify the potential mechanisms of how the CXCL12/CXCR4 axis influences the pathogenesis of CNP, we tested the classical downstream pathways. The results suggested that p-Akt, p-STAT3, and p-NF-κB were more highly expressed on the inflammatory cells of the prostate derived from the CNP model and were partly suppressed after applying AMD3100 or delivering AAV-shCxcl12, indicating that the CXCL12/CXCR4 axis potentially functioned through AKT/NF-κB and STAT3 signaling to influence the pathogenesis of CNP.Conclusion Our study provides potential diagnostic biomarkers and therapeutic targets for CNP.
研究领域:
免疫学
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分子生物学
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药理学
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泌尿学
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DOI
PubMed
高影响因子
Frontiers in Oncology
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2023
·
IF 4.7
Lin Li,Junyu Li
Background Tumor mutational burden (TMB) plays an important role in the evaluation of immunotherapy efficacy in lung adenocarcinoma (LUAD). Objective To improve the clinical management of LUAD by investigating the prognostic value of TMB and the relationship between TMB and immune infiltration. Methods TMB scores were calculated from the mutation data of 587 LUAD samples from The Cancer Genome Atlas (TCGA), and patients were divided into low-TMB and high-TMB groups based on the quartiles of the TMB score. Differentially expressed genes (DEGs), immune cell infiltration and survival analysis were compared between the low-TMB and high-TMB groups. We queried the expression of genes in lung cancer tissues through the GEPIA online database and performed experimental validation of the function of aberrant genes expressed in lung cancer tissues. Results We obtained sample information from TCGA for 587 LUAD patients, and the results of survival analysis for the high- and low- TMB groups suggested that patients in the high-TMB group had lower survival rates than those in the low-TMB group. A total of 756 DEGs were identified in the study, and gene set enrichment analysis (GSEA) showed that DEGs in the low-TMB group were enriched in immune-related pathways. Among the differentially expressed genes obtained, 15 immune-related key genes were screened with the help of ImmPort database, including 5 prognosis-related genes (CD274, PDCD1, CTLA4, LAG3, TIGIT). No difference in the expression of PDCD1, CTLA4, LAG3, TIGIT in lung cancer tissues and differential expression of CD274 in lung cancer tissues. Conclusions The survival rate of LUAD patients with low TMB was better than that of LUAD patients with high TMB. CD274 expression was down regulated in human LUAD cell lines H1299, PC-9, A549 and SPC-A1, which inhibited malignant progression of A549 cells.
研究领域:
肿瘤学
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免疫学
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基因组学
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生物信息学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
·
IF 5.988
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.
研究领域:
药理学
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神经科学
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分子生物学
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生物信息学
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实验医学
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产品关联
DOI
PubMed
高影响因子
Journal of Cosmetic Dermatology
·
2022
·Vol. 21
·期 11
·6145-6155
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IF 2.189
Jiahong Guo,Xiaoyu Ma,Fernando Bouffard,Sophia Yi Zhang
Background Fruit acids have long been recognized as highly effective actives with world-wide popularity, covering skin peeling, anti-acne, anti-wrinkle applications, and skin depigmentation. Aims There are complicated interconnections between the fruit acid formula and skin pigmentation behaviors. However, the lack of systematic researches on multi-ingredient formula restricted our understanding on its mechanism. Therefore, it is of great necessity to study the interactions and cascades among components, potential gene targets, signaling pathways, and biological processes via a system biology approach. Methods We used system biology, molecular fingerprint, and structural biology to calculate and collect target information of the functional formula. Gene Ontology (GO) enrichment analysis was further applied to study the biological processes and pathways of the formula, and a multi-level network model of “component - molecular target - signaling pathway - skin disease” was established. Besides, the zebrafish model was utilized to verify the formula. Results We obtained 69 hub targets by constructing a protein–protein interaction (PPI) network based on the intersection between multi-fruit acids formula (mandelic acid, lactobionic acid, niacinamide, and hydroxytyrosol) and skin indications targets (whitening-sebum balance). In vitro zebrafish models, including pigmentation, antioxidant, and radiation protection models, showed that the current formula significantly alleviated pigmentation intensity and intracellular free radical content, thus proving the efficacy of skin brightening and UV irradiation protection. Conclusions This research uncovered the underlying mechanism of multi-fruit acids formula and predicted its function in skin brightening and UV irradiation prevention.
研究领域:
化妆品学
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分子生物学
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药理学
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系统生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Zhejiang University-SCIENCE B
·
2023
·Vol. 24
·期 3
·207-220
·
IF 5.1
Yuan Meng,Wu Qian,Zhang Mingyang,Lai Minshan,Chen Wenbo,Yang Jianfeng,Jiang Li,Cao Ji
A series of chemotherapeutic drugs that induce DNA damage, such as cisplatin (DDP), are standard clinical treatments for ovarian cancer, testicular cancer, and other diseases that lack effective targeted drug therapy. Drug resistance is one of the main factors limiting their application. Sensitizers can overcome the drug resistance of tumor cells, thereby enhancing the antitumor activity of chemotherapeutic drugs. In this study, we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms. We found that the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, propidium iodide (PI) staining, and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia (FA) repair pathway, exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs. Thus, our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.
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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癌症治疗
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Gai Gao,Jie Zhao,Jing Ding,Shuyan Liu,Yanyan Shen,Changxin Liu,Huifen Ma,Yu Fu,Jiangyan Xu,Yiran Sun,Xiaowei Zhang,Zhenqiang Zhang,Zhishen Xie
Background The occurrence of hyperlipidemia is significantly influenced by lipid synthesis, which is regulated by sterol regulatory element binding proteins (SREBPs), thus the development of drugs that inhibit lipid synthesis has become a popular treatment strategy for hyperlipidemia. Alisol B (ALB), a triterpenoid compound extracted from Alisma , has been reported to ameliorate NASH and slow obesity. However, the effect of ALB on hyperlipidemia and mechanism are unclear. Purpose To examine the therapeutic impact of ALB on hyperlipidemia whether it inhibits SREBPs to reduce lipid synthesis. Study Design HepG2, HL7702 cells, and C57BL/6J were used to explore the effect of ALB on hyperlipidemia and the molecular mechanism in vivo and in vitro . Methods Hyperlipidemia models were established using western diet (WD)-fed mice in vivo and oleic acid (OA)-induced hepatocytes in vitro . Western blot, real-time PCR and other biological methods verified that ALB regulated AMPK/mTOR/SREBPs to inhibit lipid synthesis. Cellular thermal shift assay (CETSA), molecular dynamics (MD), and ultrafiltration-LC/MS analysis were used to evaluate the binding of ALB to VDAC1. Results ALB decreased TC, TG, LDL-c, and increased HDL-c in blood, thereby ameliorating liver damage. Gene set enrichment analysis (GSEA) indicated that ALB inhibited the biosynthesis of cholesterol and fatty acids. Consistently, ALB inhibited the protein expression of n-SREBPs and downstream genes. Mechanistically, the impact of ALB on SREBPs was dependent on the regulation of AMPK/mTOR, thereby impeding the transportation of SREBPs from endoplasmic reticulum to Golgi apparatus. Further investigations indicated that the activation of AMPK by ALB was independent on traditional CAMKK2 and LKB1. Instead, ALB resulted in a decrease in ATP levels and an increase in the ratios of ADP/ATP and AMP/ATP. CETSA, MD, and ultrafiltration-LC/MS analysis indicated that ALB interacted with VDAC1. Molecular docking revealed that ALB directly bound to VDAC1 by forming hydrogen bonds at the amino acid sites S196 and H184 in the ATP-binding region. Importantly, the thermal stabilization of ALB on VDAC1 was compromised when VDAC1 was mutated at S196 and H184, suggesting that these amino acids played a crucial role in the interaction. Conclusion Our findings reveal that VDAC1 serves as the target of ALB, leading to the inhibition of lipid synthesis, presents potential target and candidate drugs for hyperlipidemia.
研究领域:
药理学
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分子生物学
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生物化学
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细胞生物学
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代谢
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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）