CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Xinmin Zheng,Xiang Li,Guolin Shi,Yidan Zhou,Jinxiao Yan,Hao Zhang,Xiru Liu,Jiangong Zhang,Yu Liu,Liangliang Dai,Hui Yang
The low targeting of immunity regulators & chemotherapy drugs and immune tolerance in the tumor microenvironment significantly hindered the chemo-immunotherapy effect. In this work, an MMP-2/GSH-responsive nanobomb loading Resiquimod (R848) and prodrug Cisplatin (Pt) with hierarchical drug delivery and tumor associated macrophages (TAMs) polarization traits was designed for improved chemo-immunotherapy. The Pt-carrying dendrimers penetrate the depth of tumor tissues under MMP-2 and activate the cytotoxicity of Pt prodrug in response to GSH, causing effective tumor damage and enhancing immunogenicity. Meanwhile, R848 is effectively uptake by TAMs, which were re-educated and then greatly relieved immune resistance. In vitro and in vivo results collectively revealed that the nanosystem could not only overcome the barrier of tumor penetration and the heterogeneity action sites of drugs but also re-educate TAMs and suppress immune evasion via activating extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signal pathway regulated by heparin binding EGF like growth factor ( Hbegf ) gene. The gene silencing or knockout in vitro and in vivo demonstrated that Hbegf could regulate the re-education of TAMs and the progression of tumors.
研究领域:
肿瘤学
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免疫学
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药剂学
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产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2025
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IF 8.3
Xinyuan Jiang,Zhiyong Xu,Huan Wang,Jiangnan Zhao,Nueraili Maihemuti,Sujing Jiang,Mingshu Xiao,Kaiyue Zhang,Sibei Liang,Yueli Shi,Kai Wang
Background and purpose : As a malignant tumor characterized by a dismal prognosis and a high mortality rate, non-small cell lung cancer (NSCLC) presents significant challenges in contemporary treatment. These challenges include drug resistance and side effects, which severely hamper the effectiveness of current therapeutic strategies. An increasing number of herbal formulas have been utilized in antitumor therapy, owing to their cost-effectiveness, beneficial efficacy, and additional advantages. FuZhengXiaoJi Decoction (FZXJD), a cancer-treating formula, has been successfully applied in NSCLC clinical treatment, but the underlying mechanism remains elusive. Therefore, this paper integrated multiple analytical methods, including network pharmacology, metabolomics, biological approaches, and molecular docking to clarify how FZXJD suppresses NSCLC. Methods : This study assessed the anti-NSCLC efficacy of FZXJD using in vitro assays and lung cancer xenograft models, and the primary components and potential mechanisms of FZXJD inhibition of NSCLC were identified by high-performance liquid chromatography (HPLC) and network pharmacology. Subsequently, inhibitory mechanisms of FZXJD and its principal effector component oleanolic acid (OA) on NSCLC were explored by molecular docking, as well as biological experiments. Finally, effects of FZXJD on critical metabolic pathways in tumors were further investigated by metabolomics and metabolite enrichment analysis. Results : Inhibition of FZXJD on NSCLC cells was confirmed in vitro experiments. Correspondingly, in vivo experiments revealed that FZXJD impeded tumor progression without obvious toxic side effects. Network pharmacology and molecular docking disclosed that target genes involved in FZXJD’s inhibition of NSCLC were significantly enriched in the PI3K/AKT and ERK/MAPK signaling pathways. Additionally, 14 core genes (HSP90AA1, VEGFA, AKT1, JUN, EGFR, CASP3, ESR1, ERBB2, STAT3, MTOR, SRC, MDM2, CCND1, MAPK3) as well as the main component of the antitumor effect of FZXJD, the OA, were also identified. Biological experiments and molecular docking demonstrated that FZXJD and OA exerted antitumor effects by inhibiting two significant pathways, PI3K/AKT and ERK/MAPK. Metabolomics analysis indicated that FZXJD treatment suppressed glutathione metabolism in vivo. Conclusion FZXJD and its main active ingredient, OA, impede NSCLC progression by inhibiting PI3K/AKT and ERK/MAPK signaling pathways. FZXJD treatment also markedly attenuates glutathione metabolism. This research provides a promising strategy for the application of herbal formulas in NSCLC.
研究领域:
肿瘤学
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中药学
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生物信息学
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药理学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
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2024
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IF 5.5
Hu Hui,Yuheng Song,Hongmei Liu,Jiahui Fan,Zhou Sha,Hongchuang Li,Jian Lu,Qian Zhang,Xiang Fei,Meifang Zhu
Artificial periosteum is deemed a novel strategy for inducing endogenous bone regeneration, but ideal periosteum substitutes achieved by orchestrating a biomimetic microenvironment for bone regeneration remain a significant challenge. Here, we design and fabricate a hybridized nanofiber-based artificial periosteum with boosted osteoinduction properties. Via a “molecular cage” biomineralization strategy, nano-hydroxyapatite (nano-HAp) with a controllable size (∼22 nm) and excellent dispersion serves as unique nano-additives for water-soluble polyvinyl-alcohol (PVA)-based artificial periosteum. The PVA/HAp composite is electrospun into nanofibers to replicate the extracellular-matrix-inspired nanostructure for inducing cell adhesion, proliferation, and fate manipulation. A simple post-crosslinking treatment is subsequently applied to further booster its mechanical strength (6.6 MPa) and swelling stability. The optimized sample of C-PVA/HAp (10 wt% nano-HAp) artificial periosteum features excellent biocompatibility and remarkable in vitro mineralization. Cell experiments demonstrate that its effectively boasted cell modulation for enhanced osteogenesis without the aid of growth factors, showing a possible activation of the ERK/MAPK signaling pathway. This work provides an effective strategy for designing novel HAp nano-additives and expands the possibility of biomimetic fabrication for more advanced nanofiber-based artificial periosteum.
研究领域:
生物材料
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组织工程
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骨再生
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
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2023
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IF 8.8
Chen Hong,Yifan Zhang,Lili Yang,Haoyang Xu,Kang Cheng,Zhi Lv,Kaixian Chen,Yiming Li,Huali Wu
Epimedin B (EB) is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim., a traditional herb widely used in China. Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase (TYR). However, the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear. Herein, as an extension to our previous investigation, we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and elucidate the melanogenesis mechanism by assessing its effects on the TYR family of proteins (TYRs) in terms of expression, activity, and stability. The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt (referred to as protein kinase B [PKB])/glycogen synthase kinase 3β (GSK3β)/β-catenin, p-p70 S6 kinase cascades, and protein 38 (p38)/MAP kinase (MAPK) and extracellular regulated protein kinases (ERK)/MAPK pathways, after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues. Furthermore, EB exerted repigmentation by stimulating TYR activity in hydroquinone- and N -phenylthiourea-induced TYR inhibitive models, including melanoma cells, zebrafish, and mice. Finally, EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding, TYR-related protein 1 formation, and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes. These data conclude that EB can target TYRs and alter their expression, activity, and stability, thus stimulating their pigmentation function, which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.
研究领域:
药理学
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化妆品学
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细胞生物学
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分子生物学
✓ 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）