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Foods · 2025 ·Vol. 14 ·期 6 ·1026 · IF 5.1

Anti-Melanoma Activity and Potential Mechanism of Purified Potato Protease Inhibitor

Qiuyan Li,Lu Jiang,Ni Chen,Xingzhi Wang,Jiajun Yao,Zhien Su,Suqing Zhao

Melanoma is one of the most lethal cancers originating from melanocytes. Its incidence and mortality have been rising rapidly for several decades and have posed a serious threat to human health. Current melanoma treatments are hindered by the scope of application, low efficiency, high cost, and toxic side effects. Due to their affordability and minimal side effects, natural bioactive compounds derived from plants are promising candidates for melanoma treatment. This study aims to delve into the isolation, purification, and characterization of potato proteins and to explore their potential in melanoma treatment. Two potato proteins, patatin PP-1 and aspartate protease inhibitor PP-2, were isolated and purified by a newly developed method in this work, and their physicochemical properties were systematically characterized. Both potato proteins showed great antiproliferative activities and migration inhibition effects on melanoma cells. Meanwhile, Western blotting results illustrated that they could induce endogenous cell apoptosis by regulating the Bax/Bcl-2 pathway. Notably, aspartate protease inhibitor PP-2 demonstrated the best performance in inhibiting the growth and migration of melanoma cells, which might be attributed to the combined effect of its significant antioxidative activity and the inhibition effect of certain necessary protease activities in melanoma. This study provides valuable insights for developing nutraceuticals and therapeutic strategies against melanoma, which can lead to breakthroughs in melanoma treatment.

CAS / MDL: 9005-64-5
研究领域: 肿瘤学 · 药理学 · 植物化学
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FOOD AND CHEMICAL TOXICOLOGY · 2022 · IF 5.572

Microplastics and di (2-ethylhexyl) phthalate synergistically induce apoptosis in mouse pancreas through the GRP78/CHOP/Bcl-2 pathway activated by oxidative stress

Yuqi Wang,Yilei Zhang,Xinyue Sun,Xu Shi,Shiwen Xu

With the widespread use of plastics, microplastics (MPs) and di(2-ethylhexyl) phthalate (DEHP) have become emerging environmental pollutants. The combined toxicity of MPs and DEHP on the mouse pancreas and the specific mechanism of toxicity remain unclear. To establish in vitro and in vivo models to address these questions, mice were continuously exposed to 200 mg/kg/d DEHP and 10 mg/L MPs for 4 weeks. In vitro, MIN-6 cells were treated with 200 μg/mL MPs and 200 μM DEHP for 24 h. Based on toxicity assessed using CCK8 of the equivalent TU binary mixture, the IC50 of the TU-mix of DEHP and MPs 0.692 < 0.8, indicating a synergistic effect of the two toxicants. Meanwhile, our data revealed that compared to the control group, MPs and DEHP combined treatment increased ROS levels, inhibited the activity, and enhanced the expression of GRP78 , and CHOP. Simultaneously, activated CHOP decreased the expression of Bcl-2, and increased the expression of Bax. In conclusion, DEHP and MPs synergistically induce oxidative stress , and activate the GRP78/CHOP/Bcl-2 pathway to induce pancreatic apoptosis in mice. Our finding provides a new direction for the research on the specific mechanism of MPs and DEHP combined toxicity.

CAS / MDL: 8001-30-7 117-81-7
研究领域: 环境毒理学 · 细胞生物学 · 分子生物学
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BIOLOGICAL & PHARMACEUTICAL BULLETIN · 2020 · IF 1.863

Galangin Reverses Hepatic Fibrosis by Inducing HSCs Apoptosis via the PI3K/Akt, Bax/Bcl-2, and Wnt/β-catenin Pathway in LX-2 Cells

Yuanguo Xiong,Hao Lu,Hanlin Xu

Hepatic fibrosis (HF) is a common disease, with currently no available treatment. Galangin, a natural flavonoid extracted from Alpinia officinaruim Hance, has multiple effects demonstrated in previous studies. The aim of the present study was to explore the anti-fibrogenic effect of galangin in vitro, and research its potential molecular mechanisms. LX-2 cells were chosen as an in vitro HF model, and were treated with galangin in different concentrations. Cell viability was analyzed using Cell Counting Kit-8 (CCK-8) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis was measured using flow cytometry, and the anti-fibrogenic effect of galangin was determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunofluorescence, and western blotting. The results show that the proliferation of LX-2 cells was efficiently inhibited by galangin, and apoptosis was induced in a dose-dependent manner. Both the mRNA and protein expression of α-SMA and collagen I were markedly downregulated. Galangin also inhibited the PI3K/Akt and Wnt/β-catenin signaling pathways and increased the Bax/Bcl-2 ratio. The results of this study suggest that galangin has an anti-fibrogenic effect and may represent a promising agent in the treatment of hepatic fibrosis.

CAS / MDL: 548-83-4
研究领域: 药理学 · 细胞生物学 · 分子生物学 · 肝病学
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JOURNAL OF CONTROLLED RELEASE · 2023 · IF 10.8

Selective homing of brain-derived reconstituted lipid nanoparticles to cerebral ischemic area enables improved ischemic stroke treatment

Dan Han,Meihua Wang,Ningyu Dong,Jiaxing Zhang,Dingran Li,Xiaoling Ma,Ying Ma,Siliang Wang,Yun Zhu,Cheng Wang

Lipid nanoparticles (LNPs) hold great promise as carriers for developing drug delivery systems (DDSs) aimed at managing ischemic stroke (IS). Previous research has highlighted the vital role played by the lipid composition and biophysical characteristics of LNPs, influencing their interactions with cells and tissues. This understanding presents an opportunity to engineer LNPs tailored specifically for enhanced IS treatment. We previously introduced the innovative concept of reconstituted lipid nanoparticles (rLNPs), which not only retain the advantages of conventional LNPs but also incorporate lipids from the originating cell or tissue. Brain-derived rLNPs (B-rLNPs) exhibit significantly superior accumulation within the cerebral ischemic region when compared to liver-derived rLNPs (L-rLNPs). The homing effect of B-rLNPs was then employed to construct 3-n-butylphthalide (NBP) loaded DDS (B-rLNPs/NBP) for the treatment of IS. Our results demonstrated that compared with free NBP, B-rLNPs/NBP can significantly reduce infarct volume, neurological deficits, blood-brain barrier (BBB) leakage rate, brain water content, neutrophil infiltration, alleviate pathological structures, and improve the motor function in MCAO/R model. We also proved that B-rLNPs/NBP showed further reinforced protective effects on the same model than free NBP through the regulation of TLR4/MyD88/NF-κB (anti-inflammation) and Bax/Bcl-2 (anti-apoptosis) pathways. This study offers a promising tool towards improved IS treatment.

研究领域: 神经科学 · 药学 · 生物技术 · 纳米技术
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Advanced Therapeutics · 2024 ·Vol. 7 ·期 8 ·2400045 · IF 3.7

Enhanced Precision Immunotherapy of Colorectal Cancer through Chemo-Photothermal Nanoparticles via Endoplasmic Reticulum Stress Mediated Apoptotic Pathways

Shanshan Wang,Zhiqiang Bi,Tianming Lu,Ruoning Qian,Jie Yu,Qiang Zhang,Hao Yang,Wenli Lu,Yuanyuan Guo,Xiaoqing Xin,Yong Bian,Ruogu Qi

Colorectal cancer (CRC) stands out as one of the most prevalent gastrointestinal cancers. Current treatment strategies for CRC are significantly hindered by systemic toxicity and suboptimal therapeutic efficacy. This study aims to overcome these limitations by developing a robust tumor-targeting chemo-photothermal strategy, combining Bortezomib (BTZ) as a proteasome inhibitor, IR780 iodide as a near-infrared dye, and Photothermal Therapy (PTT) agent, with hyaluronic acid (HA) serving as the shell for tumor targeting, denoted as HA/PB@IR780. The investigations reveal the impressive tumor-targeting affinity of HA/PB@IR780, leading to a synergistic chemo-photothermal therapeutic effect both in vitro and in vivo. Additionally, this material demonstrates the capability for drug release triggered by low pH conditions. Moreover, HA/PB@IR780 induced the generation of reactive oxygen species (ROS), triggered cells apoptosis via the PERK-CHOP-Bcl-2 pathway, and induced Immunogenic Cell Death (ICD) in CT26 cells. Importantly, HA/PB@IR780 selectively targets tumor sites, mitigating systemic toxic side effects and significantly extending the survival of CT26 tumor-bearing mice. In conclusion, this designed tumor-targeting nanocarrier represents a promising and potentially effective platform for the precise treatment of CRC.

CAS / MDL: 331-39-5
研究领域: 肿瘤学 · 纳米技术 · 药理学 · 细胞生物学 · 治疗学
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JOURNAL OF CONTROLLED RELEASE · 2025 · IF 11.5

Fluorinated albumin nanocages dually target CAFs and tumor cells to potentiate bladder cancer chemoimmunotherapy

Zhijun Miao,Anan Xu,Gang Shen,Siyi Tang,Jie Luo,Jiajian Yang,Zhe Chen,Jinxian Pu,Tao Yang

Immunogenic cell death (ICD) induced by chemotherapeutics holds promise for cancer therapy, but limited drug penetration across the bladder mucosa and an immune-excluded tumor microenvironment (TME) have hindered success in bladder cancer. Here, we develop fluorinated albumin nanocages as transmucosal delivery vesicles that concurrently target cancer-associated fibroblasts (CAFs) and tumor cells to potentiate chemoimmunotherapy. Surface fluorination enables mucosal penetration, while recognition of secreted protein acidic and cysteine-rich (SPARC) protein ensures selective uptake by CAFs and tumor cells. Encapsulated chemotherapeutics enhance ICD through inhibition of the Bcl-2 pathway, promoting tumor cell death. Simultaneous CAF disruption reduces stromal fibrosis, facilitating anti–PD-L1 antibody delivery and T-cell infiltration. This dual-targeting strategy synergizes ICD with immune checkpoint blockade to eradicate bladder tumors by recruiting cytotoxic T cells and suppressing immunosuppressive phenotypes. Ex vivo studies in freshly resected human bladder tumors further validated the translational potential. Our findings highlight fluorinated albumin nanocages as a versatile transmucosal platform to remodel the tumor–stroma axis and amplify chemoimmunotherapy in bladder cancer.

CAS / MDL: 70024-90-7
研究领域: 肿瘤学 · 纳米医学 · 免疫治疗 · 药物递送 · 癌症生物学
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