Communications Biology
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2025
·Vol. 8
·期 1
·1-15
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IF 5.1
Wang Xue,Yan Guangqi,Li Hao,Wang Chunyu,Kang Ye,Wang Shengli,Liu Wei,Lin Lin,Zou Renlong,Zeng Kai,Wang Manlin,Luan Ruina,Zhou Baosheng,Bai Yu,Yang Dongjun,Ning Bolin,Sun Ge,Zhao Yue
Oral squamous cell carcinoma (OSCC) progresses from epithelial cell proliferation to malignancy. Given the higher proportion of male patients compared to female patients, the androgen signaling pathway is believed to play a significant role in promoting epithelial cell proliferation. However, the underlying molecular mechanisms remain unclear. Here, we identified RBAP48 as a novel androgen receptor (AR) co-activator in OSCC cells. Our results show that RBAP48 was highly expressed in OSCC tumor tissues from patients with a poor prognosis. Further, RBAP48 knockdown decreased genome-wide oncogene transcription. RBAP48 and AR interacted to activate CCND1 and RAB31 transcription, and upregulated RELA and CCNE1 mRNA expression through an AR-independent pathway. Additionally, RBAP48 promoted OSCC cell proliferation and was involved in the cellular response to drugs and external compounds in vitro, ultimately driving cancer progression. Our results indicate that RBAP48 is a novel oncogene and a promising target for predicting and treating OSCC progression.
研究领域:
肿瘤学
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分子生物学
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医学遗传学
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DOI
PubMed
高影响因子
MOLECULAR DIVERSITY
·
2026
·
IF 4.3
Hou Yingdong,Wang Zhijie,Xia Hubin,Zhou Yifeng,Zhang Xiaofeng
Dioctyl terephthalate (DOTP) has been associated with chronic intestinal inflammation. However, its implications for patients with colorectal cancer (CRC) remain unexplored. This study aimed to identify potential molecular targets and mechanisms involved in DOTP-related remodeling of the CRC microenvironment. Using multiple databases and weighted gene coexpression network analysis, we identified 12 potential DOTP-related CRC targets. Molecular docking (MD) and molecular dynamics simulations (MDS) were conducted to assess the interactions between these targets and DOTP. Notably, potential bindings were observed between DOTP and nine targets. Through the screening of 82 machine learning model combinations, four common targets were identified among the nine candidates, particularly RELA and AR. Importantly, exposure of SW620 and LS513 to DOTP resulted in increased RELA expression and enhanced proliferative and migratory capacities. Furthermore, elevated RELA expression was associated with an immunosuppressive microenvironment and a reduced response to immunotherapy. Single-cell RNA sequencing (scRNA-seq) revealed predominant RELA expression in macrophages, particularly in M2-like Mph_SPP1 cells, which exhibited marked immunosuppressive activity with highly expressed LGALS9. Notably, THP1 cells treated by DOTP resulted in increased mRNA expression levels of RELA and M2 phenotype markers. These findings suggest that dysregulation of the immune microenvironment may represent a critical mechanism underlying the progression of DOTP-related CRC and highlight RELA as a promising therapeutic target for CRC patients with high-risk exposure to DOTP.
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DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2023
·Vol. 21
·期 1
·1-14
·
IF 7.4
Chen Shengnan,Li Bo,Chen Lei,Jiang Hongli
Background Diabetic kidney disease (DKD) has been the leading cause of chronic kidney disease in developed countries. Evidence of the benefits of resveratrol (RES) for the treatment of DKD is accumulating. However, comprehensive therapeutic targets and underlying mechanisms through which RES exerts its effects against DKD are limited.Methods Drug targets of RES were obtained from Drugbank and SwissTargetPrediction Databases. Disease targets of DKD were obtained from DisGeNET, Genecards, and Therapeutic Target Database. Therapeutic targets for RES against DKD were identified by intersecting the drug targets and disease targets. GO functional enrichment analysis, KEGG pathway analysis, and disease association analysis were performed using the DAVID database and visualized by Cytoscape software. Molecular docking validation of the binding capacity between RES and targets was performed by UCSF Chimera software and SwissDock webserver. The high glucose (HG)-induced podocyte injury model, RT-qPCR, and western blot were used to verify the reliability of the effects of RES on target proteins.Results After the intersection of the 86 drug targets and 566 disease targets, 25 therapeutic targets for RES against DKD were obtained. And the target proteins were classified into 6 functional categories. A total of 11 cellular components terms and 27 diseases, and the top 20 enriched biological processes, molecular functions, and KEGG pathways potentially involved in the RES action against DKD were recorded. Molecular docking studies showed that RES had a strong binding affinity toward PPARA, ESR1, SLC2A1, SHBG, AR, AKR1B1, PPARG, IGF1R, RELA, PIK3CA, MMP9, AKT1, INSR, MMP2, TTR, and CYP2C9 domains. The HG-induced podocyte injury model was successfully constructed and validated by RT-qPCR and western blot. RES treatment was able to reverse the abnormal gene expression of PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR.Conclusion sRES may target PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR domains to act as a therapeutic agent for DKD. These findings comprehensively reveal the potential therapeutic targets for RES against DKD and provide theoretical bases for the clinical application of RES in the treatment of DKD.
研究领域:
药理学
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分子生物学
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糖尿病
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肾病学
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DOI
PubMed
高影响因子
JOURNAL OF TOXICOLOGICAL SCIENCES
·
2019
·
IF 1.732
Yunsong Zhou,Chong Peng,Zunming Zhou,Keer Huang
Several studies have demonstrated the chemopreventive role of ketoconazole in animal models of liver injury. However, the underlying molecular mechanisms of this hepatoprotective effect are poorly understood. The present study assessed the potential of ketoconazole to enhance resistance to carbon tetrachloride-induced hepatotoxicity in vivo in a rat model. Ketoconazole pretreatment adult male rats were intraperitoneally injected with carbon tetrachloride for 24 hr and various hepatic parameters were analyzed. We observed decreased serum transaminases activity, reduced nuclear RelA/p65 expression, and suppressed production of pro-inflammatory cytokines in the liver tissue. Histopathological examination demonstrated ketoconazole pretreatment to extensively prevent liver injury. In addition, it significantly increased nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) protein expression, glutathione (GSH) to oxidized glutathione (GSSG) ratio, and antioxidant enzymes gene expression. These results suggest that ketoconazole pretreatment ameliorates carbon tetrachloride-induced acute liver injury in rats, signifying its anti-inflammatory and antioxidant functions.
研究领域:
药理学
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毒理学
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肝病学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
·
IF 4.8
Chen-chen Wu,Jing-yao Ge,Xin-yue Huang,Xiao-ming Liu,Yan Liao,Shui-jing Zhang,Lin Wu,Xiao-fan Chen,Bo Yu
Rosacea is a chronic inflammatory skin disease, which is prone to flares and requires continuous management and treatment. However, long-term use of drugs can lead to additional adverse drug reactions. Based on the comorbid relationship between rosacea and Parkinson’s disease, bioinformatics and network pharmacology analysis were used to identify a safer drug for rosacea. It has been demonstrated that ISA has an ameliorative impact on the symptoms of Parkinson’s disease. The results demonstrated that ISA exhibited anti-inflammatory properties, including reducing erythema areas and inflammatory cell infiltration in rosacea-like mice models, and inhibiting the expression of inflammatory factors in cellular inflammation models. Furthermore, the anti-inflammatory effect of ISA was associated with inhibition of the Erk, p38 and NF-κB signaling pathways and inhibition of macrophage polarization to M1 type. In addition, molecular docking and drug affinity responsive target stability experiment results indicated that VEGFA and RELA were the direct targets of ISA in the treatment for rosacea. In conclusion, these results suggested that ISA may be a potential therapeutic agent for rosacea.
研究领域:
皮肤科
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药理学
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炎症研究
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神经学
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产品关联
DOI
PubMed
高影响因子
Journal of Oleo Science
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2022
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IF 1.628
Chunlian Li,Qiuyang Cai,Xianyi Wu,Zekai Tan,Lewen Yao,Shiyuan Huang,Weicheng Zhang,Zhengyi Hong,Zhuoyu Chen,Lanyue Zhang
Umbelliferae plants, which are widely used as traditional Chinese medicine because of their characteristics of relieving rheumatism, alleviating fever, circulating blood and easing pain. This experimental study was based on ear edema model caused by 12-O-tetracycline-propylphenol-13-acetic acid (TPA) in mice and compared with the Ibuprofen (Ib) group. Gas chromatography-mass spectrometry (GC-MS) was used to analyse the composition of the essential oils from the four studied Umbelliferae plants (Angelica sinensis (Oliv.) Diels, A. dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., A. pubescens Maxim and Foeniculum vulgare Mill.). Biologically active components in volatile oils from the four studied Umbelliferae plants were evaluated. The expression levels of inflammatory cytokines Tumor Necrosis Factor-α (TNF-α), Cyclooxygenase-2 (COX-2), Interleukin-6 (IL-6) and RelA (p65) in mouse skin were determined by immunohistochemical method. The refractive index of the four essential oils was calculated. A total of 239 compounds were identified by GC-MS from the four studied plants, and the main constituents were osthole (44.61%, APEOs), obepin (0.59%, APEOs & 86.58%, FVEOs), undecanol (8.58%, ADEOs), α-muurolene (7.95%, ADEOs) and cis-anethol (9.11%, ADEOs). E-ligustilide (0.14%, APEOs & 81.14%, ASEOs), (-)-spathulenol (0.08%, FVEOs & 1.21%, ASEOs), (-)-terpinen-4-ol (4.91%, FVEOs), 2-butylthiolane (5.76%, APEOs) and α-bisabolol (3.80%, APEOs). This study showed that all the essential oils from the four studied Umbelliferae plants contained various lactones, including ligustrongolactone, trans-anisol and imperatorin. According to the results of the TPA induction test in the mouse ear edema model, the essential oils of four Umbelliferae plants reduced the levels of inflammatory cytokines TNF-α, COX-2, IL-6 and p65. All of them showed extraordinary biological activity in anti-inflammatory, so they have potential application value for biomedical products, pharmaceutical preparations, natural functional nutrients and cosmetic additives.
研究领域:
药理学
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药物化学
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中医药学
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免疫学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Min Hao,Zhouhui Yao,Mengting Zhao,Ziyan Chen,Pingping Wang,Xianan Sang,Qiao Yang,Kuilong Wang,Xin Han,Gang Cao
Ethnopharmacological relevance Curcumae Rhizoma-Sparganii Rhizoma (CR-SR) is a classic herbal pair to promote blood circulation and remove blood stasis in ancient China. However, the molecular mechanism is still unclear. Aim of study To screen out the anti-liver fibrosis active ingredients in CR-SR. Moreover, preliminary exploration the molecular mechanism of CR-SR to ameliorates liver fibrosis . Materials and methods In this research, plant taxonomy has been confirmed in the “The Plant List” database ( www.theplantlist.org ). The chemical components of CR-SR were analysed by ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). “Component-Target-Pathway-Disease” network of CR-SR components were built by network pharmacology . Then, the interaction between primary components and predicted protein targets based on network pharmacology were validated by molecular docking. The pharmacological actions of CR-SR were verified by blood biochemical indexes, histopathologic examination of CCL 4 induced rats’ model. The core protein targets were verified by Western blot . The effects of screened active components by molecular autodocking were verified by HSC-T6 cell experiment. Results The result shows that 57 chemical constituents in CR-SR herbal pair were identified by UPLC-Q/TOF-MS, in which, 27 compounds were closely connected with liver fibrosis related protein targets. 55 protein targets screened out by “component-target-pathway-disease network” maybe the underlying targets for CR-SR to cure liver fibrosis. Moreover, the 55 protein targets are mainly related to RNA transcription, apoptosis , and signal transduction. The molecular autodocking predicted that ten components can bond well with PTGS2 and RELA protein targets. The blood biochemical indexes, histopathologic examination of CCL 4 induced rats experiment showed that CR-SR has well intervention effect of liver fibrosis. The Western blot analysis indicated that CR-SR could significantly inhibit RELA, PTGS2, IL-6, SRC, and AKT1 protein expression to exert the anti-fibrosis effect. The HSC-T6 cell experiment indicated that both formononetin (FNT) and curdione could significantly inhibit the activation of HSC and reduce the expression of PTGS2, and p-AKT1 which was accordance with the molecular autodocking results. Conclusion This study proved the molecular mechanism of CR-SR multi-component and multi-target anti-liver fibrosis effect through mass spectrometry, network pharmacology, and western blotting technology. The research provides a theoretical evidence for the development and utilization of CR-SR herbal pair.
研究领域:
药理学
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分子生物学
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网络药理学
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中药学
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肝病
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产品关联
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
·
2024
·
IF 5.3
Dong Xie,Guangfu Lv,Yuchen Wang,Wenjing Zhang,Nian Li,Yao Duan,Qing Huang,Ge Chen,Zifeng Pi,Hao Yue
Tenghuang Jiangu Wan (THJGW) is a commonly utilized treatment for osteoarthritis (OA), yet its pharmacodynamic material basis and molecular mechanism remain inadequately understood. This study systematically characterized the in vitro and in vivo chemical components of THJGW using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The pharmacodynamic material basis of THJGW in the treatment of OA was explored through a target network pharmacology approach and molecular docking technology. Cellular experiments were subsequently employed to validate the molecular mechanisms. Consequently, a total of 134 components from THJGW were identified in vitro , comprising 45 flavonoids, 10 iridoid glycosides, 39 phenylethanoid glycosides, 9 phenylpropanoids, 11 organic acids, 4 phenolics, and 16 other compounds. Additionally, 38 prototype absorbed components in serum were characterized for the purpose of network construction. 11 key components and 10 core targets (VEGFA, STAT3, RELA/NF-κB p65, PIK3R1, PIK3CA, MMP9, MMP1, IL-6, HDAC1, and FGF2) were determined by the target network pharmacology. Through Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it was found that these intersection targets are associated with various signaling pathways such as pathways in cancer, lipid and atherosclerosis, and prostate cancer. Notably, the lipid and atherosclerosis pathway was closely linked to OA. The molecular docking results demonstrated strong binding affinities of the three core targets: IL-6, STAT3, and RELA/NF-κB p65. These results suggest that these targets may play a significant role for THJGW in treating OA. In vitro experiments showed that THJGW had notable protective effects on LPS-induced RAW264.7 macrophages by reducing levels of TNF-α and IL-6, and inhibiting phosphorylation expression of STAT3 and NF-κB p65 proteins related to the lipid and atherosclerosis pathway. This study provides insight into the pharmacodynamic material basis and mechanism of action for THJGW in the treatment of OA, which provide scientific evidence for the scientific application and improvement of quality standards for THJGW.
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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中医药
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产品关联
DOI
高影响因子
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