Journal of Advanced Research
·
2025
·
IF 13
Jia Xu,Bingxin Huangfu,Teng Wang,Xinxin Ren,Feng Zhang,Kunlun Huang,Xiaoyun He
Introduction The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is rising, while current pharmacological treatments are often limited by adverse effects. Artemether (Art), a derivative of artemisinin, has demonstrated therapeutic potential against MAFLD, but its direct molecular targets remain unclear. Objectives This work focuses on Art’s therapeutic effects and molecular targets in MAFLD. Methods In this study, MAFLD was induced in C57BL/6J male mice via high-fat diets, followed by treatment with Art at 10 or 50 mg/kg·bw/d; obeticholic acid served as a positive control. Glucose tolerance, serum biochemistry, and liver histology were assessed. Fatty acid-induced MAFLD models in HepG2 and primary mouse hepatocytes were treated with Art (5 µM or 25 µM), and lipid accumulation was evaluated. Protein target identification involved drug affinity responsive target stability (DARTS), cellular thermal shift assay (CESTA), chemical proteomics, and molecular docking etc. Heat shock protein 90 (HSP90) and epidermal growth factor receptor (EGFR) were confirmed as direct targets of Art through over-expression, inhibition, and knockdown techniques in cells and mice. Results Art dose-dependently reduced hepatic lipid accumulation in MAFLD mice and suppressed oleic-palmitic acid–induced lipid droplet formation in vitro . HSP90 and EGFR were identified as direct binding targets of Art, which disrupted the HSP90–EGFR complex, reducing EGFR stability and expression. The therapeutic efficacy of Art was not further enhanced when administered following HSP90 or EGFR knockdown, confirming that HSP90 and EGFR function as key molecular targets of Art. Conclusion These findings identify EGFR as a key target of Art, modulated directly or via HSP90, thereby offering new insights into Art’s multi-target therapeutic mechanism in MAFLD.
研究领域:
药理学
·
分子生物学
·
肝病学
·
生物化学
·
药物研发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Li Zhang,Lixia Guan,Yuting Wang,Miao-Miao Niu,Jinhu Yan
Dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) and histone deacetylase 8 (HDAC8) have been shown to be associated with the development of several cancers. Here, we identified a dual-target DYRK2/HDAC8 inhibitor (DYC-1) through a combined virtual screening protocol. DYC-1 exhibited nanomolar inhibitory activity against both DYRK2 (IC 50 = 5.27 ± 0.13 nM) and HDAC8 (IC 50 = 8.06 ± 0.47 nM). Molecular dynamics simulations showed that DYC-1 had positive binding stability with DYRK2 and HDAC8. Importantly, the cytotoxicity assay indicated that DYC-1 exhibited superior antiproliferative activity against human liver cancer, especially SK-HEP-1 cells, and had no significant inhibition on normal liver cells. Moreover, DYC-1 showed a strong inhibitory effect on the growth of SK-HEP-1 xenograft tumors with no significant side effects. These data suggest that DYC-1 is a high-efficacy and low-toxic antitumor agent for the treatment of hepatocellular carcinoma.
研究领域:
肿瘤学
·
药物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Science & Nutrition
·
2024
·Vol. 12
·期 12
·10933-10945
·
IF 3.5
Wen-Tao Chen,Jing Sun,Ying-Yang Zhang,Ying Xu,Ping Zou,Jian-Gang Hu,Lei Zhou
This comprehensive study focused on evaluating and selecting seven distinct commercial membranes to develop BTESE/PA membranes. This method effectively facilitated the extraction of cynaroside from the complex composition of peony seed meal. We subsequently conducted a thorough investigation into its biological properties. These findings establish a robust foundation for future research and the development of related products. The peak concentration achieved by peony seed meal filtration (PSMF) was 234.84 ± 1.17 μg/mL. Among the commercial membranes evaluated, the PA membrane exhibited superior separation capabilities, leading to its selection for BTESE loading. Compared with BTESE treated with HCl and NH 3 , the HCl variant, once incorporated into the BTESE/PA membrane, enhanced cynaroside separation, achieving an impressive 90.23% recovery rate. A comprehensive investigation of the biological effects of cynaroside revealed its crucial antioxidant role, especially in SOD binding. Additionally, cynaroside has the potential to induce apoptosis in K562 cells through interactions with BCL-2 and CDK-2 enzymes. Pharmacophore screening revealed the affinity of cynaroside for the PDE5A, TNKS2, and DAPK1 proteins, suggesting that it has diverse potential applications.
研究领域:
植物化学
·
药理学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PeerJ
·
2024
·
IF 2.3
Ying Zhang,Fengrui Cheng,Xingrui Cai,Jingping Wu
Background Epstein-Barr virus induced gene 3 ( EBI3 ), a member of the IL-12 family, is known to be involved in malignant progression in a variety of cancers, but its role in melanoma is unclear. The aim of this study was to explore the effects of EBI3 on the malignant phenotype melanoma to reveal its potential as a therapeutic target. Methods In this study, we used bioinformatics to analyze the expression of EBI3 in pan-cancer and verified its expression level in melanoma cells by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the effects of EBI3 knockdown on cell proliferation, migration and invasion were detected using the Cell Counting Kit-8 (CCK-8) and Transwell assays. Changes in immune-related cytokines were detected by ELISA, and macrophage polarization was observed using immunofluorescence. Finally, the phosphorylation levels of signaling pathways such as Smad3, STAT6 and cGAS-STING were analyzed by Western blot. Results EBI3 was evidently highly-expressed in melanoma, and silencing of EBI3 could visibly suppress the survival and migration/invasion of melanoma cells, concurrent with the increased levels of BAX and CDH1 and the decreased expressions of BCL2 and CDH2 . Meanwhile, EBI3 knockdown diminished the phosphorylation levels of both Smad3 and STAT6 and the levels of immune response-relevant cytokines in melanoma cells, while aggravating the macrophage M1 polarization and the expression of cGAS, p-STING and p-IRE1 α in THP-1 monocyte-derived macrophages co-cultured with EBI3 -silenced melanoma cells. Conclusion This study filled the blank on the involvement of EBI3 in melanoma, hinting the possibility of controlling EBI3 as a therapeutic strategy in the management of melanoma.
研究领域:
肿瘤学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CURRENT ORGANIC SYNTHESIS
·
2021
·Vol. 18
·期 6
·587-591
·
IF 1.975
Song Zurong,Lu Qin,Tao Ali,Wu Tianchen
Background: Paclitaxel, a natural diterpenoid compound, has anti-tumor effect by acting on tubulin, whereas coumarin, another kind of natural product, has anti-tumor effect, along with some other effects, such as anti-bacterial-., Moreover, it also possesses fluorescence. Objective:
Multi targeting is an effective strategy in drug design to combat tumor. Therefore, a combination of paclitaxel with other active molecular drugs for exploring the novel lead with multi-functions is in demand. Materials and Methods: To synthsize paclitaxel-coumarin conjugate via click
chemistry and to investigate anticancer activity by MTT assay and the scratch test. Results and Discussion: The results of MTT assay showed that compared tothe paclitaxel, the anti-tumor activity of the conjugate was significantly improved. The results of flow cytometry showed that the
conjugate had a stronger ability to induce apoptosis. The scratch test results showed that the conjugate had better anti- metastasis ability than paclitaxel. Conclusion: These findings indicated that paclitaxel and coumarin had a synergistic effect, which paved the way for the development
of paclitaxel through fluorescence.
研究领域:
药理学
·
肿瘤学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
·
IF 6.5
Zi-Yun Wu,Kang-Yu Qiu,Yan-Jun Gai,Jia-Hui Wu,Bo-Xuan Zhou,Qing-Feng Shi
Breast cancer is one of the most common cancers among women worldwide, exhibiting notably high incidence and mortality rates. Despite its high fatality, a comprehensive study that mechanism and treatment of herbal medicines has not yet been conducted. Quercetin, a natural flavonoid, exhibits multi-targeted therapeutic potential against breast cancer. The aim of this study is to investigate and assess the mechanism and treatment of quercetin in breast cancer. We collected articles published within five years using PubMed, Google Scholar, and Web of Science with “breast cancer” and “quercetin” as
研究领域:
肿瘤学
·
药理学
·
天然产物
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-19
·
IF 15.7
Zhang Yu,Zhang Tingting,Xiao Xue,Wang Yejun,Kawalek Adam,Ou Jinzhao,Ren Anmin,Sun Wenhao,de Bakker Vincent,Liu Yujie,Li Yuelong,Yang Liang,Ye Liang,Jia Ning,Veening Jan-Willem,Liu Xue
With the rise of antibiotic-resistant bacteria, non-antibiotic therapies like gallium gain increasing attention. Intravenous gallium nitrate is under Phase II clinical trials to treat chronic Pseudomonas aeruginosa infections in cystic fibrosis patients. However, its clinical efficacy is constrained by the achievable peak concentration in human tissue. To address this limitation, we apply a genome-wide CRISPR interference approach (CRISPRi-seq) to identify potential synergistic targets with gallium. We classify the essential genes by response time and growth reduction, pinpointing the most vulnerable therapeutic targets in this species. In addition, we identify a highly conserved gene, fprB , encoding a ferredoxin-NADP⁺ reductase, whose deletion sensitizes P. aeruginosa to gallium, lowering its MIC by 32-fold and shifting mode of action from bacteriostatic to bactericidal. Further investigation reveals that FprB plays a critical role in modulating oxidative stress induced by gallium, via control of iron homeostasis and reactive oxygen species accumulation. Deleting fprB enhances gallium’s efficacy against biofilm formation and improves outcomes in a murine lung infection model of P. aeruginosa , suggesting FprB is a promising drug target in combination with gallium. Overall, our data show CRISPRi-seq as a powerful tool for systematic genetic analysis of P. aeruginosa , advancing the identification of novel therapeutic targets.
研究领域:
微生物学
·
分子生物学
·
药理学
·
基因组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xian Liu,Qiwu Yuan,Yang Yang,Ke Li,Nanjiong Pang,Jiangtao Wang,Ming Yang,Xia Li,Junling Guo,Xuepin Liao,Bi Shi
Antibiotic resistance poses a significant threat to global public health, urgently demanding the development of new antibacterial agents with high efficacy and low resistance potential. In this study, we engineered self-assembled nanocomplexes of the gallic acid (GA) with rare earth (Re) ions (Ce 3+ , Gd 3+ , and Yb 3+ ), leveraging the unique multidentate structures of polyphenols to enhance antibacterial performance while minimizing resistance. These GA-Re nanocomplexes demonstrated potent activity against both antibiotic-sensitive Staphylococcus aureus (ASSA) and methicillin-resistant S. aureus (MRSA), with minimum inhibitory concentrations as low as 0.5 mmol/L. Viable MRSA cell numbers decreased from 7.40 × 10 7 CFU/mL to 8.43 × 10 6 and 7.33 × 10 2 CFU/mL when treated with penicillin (PEN) and GA-Gd for 24 h, respectively, indicating higher bactericidal efficiency of GA-Gd. Remarkably, no resistance developed in ASSA even after 60 days(d) of continuous exposure to GA-Gd, in contrast to the significant resistance observed with PEN (1024-fold) and neomycin (256-fold) after 28 d. The multidentate structure of GA facilitated versatile interactions with bacterial surface structures, enabling multiple mechanisms of action targeting cell walls, membranes, DNA, and cellular metabolism. Moreover, in vivo studies revealed that GA-Gd was effectively metabolized and excreted without accumulation or toxicity, and also accelerates the healing of MRSA infected wounds. These findings suggest the potential of self-assembled Re-based phenolic nanocomplexes as promising candidates for combating antibiotic-resistant bacterial infections, and pave the way for next-generation antibacterial agents.
研究领域:
微生物学
·
药理学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Cell and Developmental Biology
·
2022
·
IF 6.081
Gu Xinyi,Zhang Guanying,Wang Qixue,Song Jing,Li Ying,Xia Chenyi,Zhang Ting,Yang Li,Sun Jijia,Zhou Mingmei
Objective: Acanthopanax senticosus (Rupr. et Maxim.) Harms (ASH) is a traditional herbal medicine widely known for its antifatigue and antistress effects, as well as tonifying qi, invigorating spleen and kidney, and tranquilizing the mind. Recent evidence suggests that ASH has a therapeutic effect on major depressive disorder (MDD), but its mechanism is still unclear. The current study aimed to investigate the effect of ASH on MDD and potential therapeutic mechanisms.Materials and Methods: The chemical compound potential target network was predicted based on network pharmacology. Simultaneously, chronic unpredictable mild stress (CUMS) model mice were orally administrated ASH with three dosages (400, 200, and 100 mg/kg) for 6 weeks, and hepatic metabolomics based on gas chromatography–mass spectrometry (GC–MS) was carried out to identify differential metabolites and related metabolic pathways. Next, the integrated analysis of metabolomics and network pharmacology was applied to find the key target. Finally, molecular docking technology was employed to define the combination of the key target and the corresponding compounds.Results: A total of 13 metabolites and four related metabolic pathways were found in metabolomics analysis. From the combined analysis of network pharmacology and metabolomics, six targets (DAO, MAOA, MAOB, GAA, HK1, and PYGM) are the overlapping targets and two metabolic pathways (glycine, serine, and threonine metabolism and starch and sucrose metabolism) are the most related pathways. Finally, DAO, MAOA, MAOB, GAA, HK1, and PYGM were verified bounding well to their corresponding compounds including isofraxidin, eleutheroside B1, eleutheroside C, quercetin, kaempferol, and acacetin.Conclusion: Based on these results, it was implied that the potential mechanism of ASH on MDD was related to the regulation of metabolism of several excitatory amino acids and carbohydrates, as well as the expression of DAO, MAOA, MAOB, GAA, HK1, and PYGM.
研究领域:
中药学
·
神经科学
·
代谢组学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICAL VIROLOGY
·
2022
·Vol. 95
·期 1
·e28299
·
IF 20.693
Lu Lv,Leiliang Zhang
Monkeypox virus (MPXV) is a member of Orthopoxvirus in the Poxviridae family, causing a Public Health Emergency of International Concern. The number of cases and geographic range has increased significantly in 2022. Identification of MPXV-specific therapeutic targets is urgent. G-quadruplex (GQ) secondary structures attract great attention as potential targets for antiviral strategy. Whether GQs are present in the MPXV genome remains inconclusive. In this study, we aim to characterize the GQs encoded by MPXV. Through a series of biophysical experiments, we characterized the formation potential of MPXV-encoded GQs and evaluated the binding and stabilization abilities of GQ ligands including BRACO-19, pyridostatin, and TMPyP4 to GQs encoded by MPXV. Moreover, GQ ligands suppressed the gene transcription of MPXV sequences containing GQ. BRACO-19 and TMPyP4 were able to inhibit vaccinia virus replication. We demonstrated the existence of MPXV GQ and reinforced the idea that GQs could be novel antiviral targets. Targeting these GQ sequences with GQ-binding molecules may represent a new approach for MPXV therapy.
研究领域:
病毒学
·
分子生物学
·
药物开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
WORLD JOURNAL OF GASTROENTEROLOGY
·
2023
·
IF 4.3
Xiu-Yan Li,Yu-Ting Luo,Yan-Hong Wang,Zhi-Xin Yang,Yu-Zhou Shang,Qing-Xia Guan
BACKGROUND New drugs are urgently needed for the treatment of liver cancer, a feat that could be feasibly accomplished by finding new therapeutic purposes for marketed drugs to save time and costs. As a new class of national anti-infective drugs, carrimycin (CAM) has strong activity against gram-positive bacteria and no cross resistance with similar drugs. Studies have shown that the components of CAM have anticancer effects. AIM To obtain a deeper understanding of CAM, its distribution, metabolism and anti-inflammatory effects were assessed in the organs of mice, and its mechanism of action against liver cancer was predicted by a network pharmacology method. METHODS In this paper, the content of isovaleryl spiramycin III was used as an index to assess the distribution and metabolism of CAM and its effect on inflammatory factors in various mouse tissues and organs. Reverse molecular docking technology was utilized to determine the target of CAM, identify each target protein based on disease type, and establish a target protein-disease type network to ascertain the effect of CAM in liver cancer. Then, the key action targets of CAM in liver cancer were screened by a network pharmacology method, and the core targets were verified by molecular docking and visual analyses. RESULTS The maximum CAM concentration was reached in the liver, kidney, lung and spleen 2.5 h after intragastric administration. In the intestine, the maximum drug concentration was reached 0.5 h after administration. In addition, CAM significantly reduced the interleukin-4 (IL-4) levels in the lung and kidney and especially the liver and spleen; moreover, CAM significantly reduced the IL-1β levels in the spleen, liver, and kidney and particularly the small intestine and lung. CAM is predicted to regulate related pathways by acting on many targets, such as albumin, estrogen receptor 1, epidermal growth factor receptor and caspase 3, to treat cancer, inflammation and other diseases. CONCLUSION We determined that CAM inhibited inflammation. We also predicted the complex multitargeted effects of CAM that involve multiple pathways and the diversity of these effects in the treatment of liver cancer, which provides a basis and direction for further clinical research.
研究领域:
药理学
·
肿瘤学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Discover Oncology
·
2024
·Vol. 15
·期 1
·1-10
·
IF 2.8
Fan Ruizhi,Xu Teng,Kuang Yuting
Background Colorectal cancer, which originates from the human colon or rectum, is one of the leading causes of death worldwide. Timely diagnosis and interventional therapy can significantly improve the prognostic survival of colorectal cancer patients, making regular screening and early detection essential. Aim To investigate the regulatory function of lncRNA CTBP1-DT (CTBP1-DT) on colorectal cancer cells and to assess its diagnostic significance. Methods A total of 102 patients with colorectal cancer and 92 healthy individuals were selected. The levels of CTBP1-DT and microRNA-30a-5p (miR-30a-5p) in serum and cell samples of the above subjects were compared by RT-qPCR. The effects of CTBP1-DT and miR-30a-5p dysregulation on the biological functions of colorectal cancer cells were analyzed via CCK-8, flow cytometry and Transwell assays. In addition, the ability of CTBP1-DT and miR-30a-5p to early identify colorectal cancer patients was determined through ROC curve. Results Serum CTBP1-DT was elevated in patients with colorectal cancer, which was obviously higher than in healthy controls. The expression of serum miR-30a-5p was downregulated in colorectal cancer. Both CTBP1-DT and miR-30a-5p have the value of distinguishing colorectal cancer, and the combined diagnostic ability is higher. Knockdown of CTBP1-DT directly targeted miR-30a-5p to repress cell activity and metastatic ability, whereas deregulation of miR-30a-5p eliminated the above inhibitory effects. Conclusion Overexpression of CTBP1-DT has a certain application potential in the diagnosis of colorectal cancer and may be a therapeutic target for colorectal cancer.
研究领域:
肿瘤学
·
分子生物学
·
癌症生物学
·
诊断
✓ 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）