Publications by authors named "Liu-Gen Li"

Teniposide (Ten/VM-26) is low in toxicity and has proven to be effective in destroying malignant cells at low doses. However, the target and molecular mechanism of Ten/VM-26 are poorly understood, which limits its clinical application against solid malignant cancers. Apurinic/apyrimidinic endonuclease 1 (APEX1) expression is upregulated in lung cancer, which could effectively suppress DNA damage.

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Targeted promotion of iron ion accumulation and inhibition of outer membrane protein function in mitochondria contribute to ferroptosis, thereby boosting anticolorectal cancer (CRC) efficacy. Based on our previous study, the anticancer agent bortezomib (BTZ) was loaded in an iron-derived metal-organic framework (MOF), which was further modified by rhodamine B (RhB), yielding BTZ@RhB-MOF for targeted CRC treatment. Physicochemical characterization results indicated successful preparation of BTZ@RhB-MOF, which had the framework structure and nanosize properties with BTZ and iron ion release under acidic conditions.

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Pyroptosis is the critical approach for the induction of robust cancer cell death and activation of the immune microenvironment, which often results from mitochondrial damage. Herein, a combination strategy of sonodynamic-chemotherapy is designed to achieve an anti-heptocellular (HCC) effect, wherein the cepharanthine (Cep), a kind of functional phytomedicine, is loaded into the Tris(chlorisopropyl)Phosphate (TCPP) Metal-organic framework (MOF). The Cep@TCPP-MOF is successfully developed, as characterized by techniques such as transmission electron microscopy (TEM) and dynamic light scattering (DLC).

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Cerebral malaria (CM), primarily caused by , is the primary cause of malaria-related fatalities. CM treatment faces significant challenges due to limited therapeutic options and the emergence of antimalarial drug resistance. Dihydroartemisinin (DHA) is the first-line therapeutic agent for malaria.

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Sorafenib (Sor), a multi-kinase inhibitor, serves as the first-line systemic therapeutic drug for advanced hepatocellular carcinoma (HCC). Unfortunately, clinical benefit was confirmed in only a minority of patients, limiting clinical application of Sor. Using nanotechnology to enhance the therapeutic effect of anti-cancer drugs has become a major trend.

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Anti-tumor agent bortezomib (BTZ) showed poor efficacy in colorectal cancer (CRC), which is attributed to the high expression of KEAP1-NRF2, an essential anti-oxidative system. Oxidative DNA damage is one of the critical mechanisms by which photodynamic therapy (PDT) induces apoptosis in tumor cells, which can be considered an important tool for early non-invasive treatment of CRC. The present work aims to explore the role and mechanism of PDT synergizing with BTZ in the treatment of CRC.

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Background: The metastasis of hepatocellular carcinoma (HCC) leads to a poor prognosis, wherein the activation of Notch1 is an essential contributor. Cepharanthine (Cep) has been identified for its effective antiviral function and versatile intracellular targets. Our previous study has only reported the anti-cancer efficacy of Cep in lung cancer, without an in-depth exploration.

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Article Synopsis
  • The study investigates how silica exposure causes macrophages to polarize towards a pro-inflammatory state (M1 polarization) through mechanisms involving mitochondrial damage and pyroptosis.
  • Quercetin (Que) is evaluated as a potential treatment that can reverse this polarization and mitigate associated lung inflammation and fibrosis.
  • The findings suggest that Que binds to TOM70, helping to restore mitochondrial function and reduce macrophage-driven inflammatory responses, which could lead to new therapeutic strategies for treating silicosis.
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Article Synopsis
  • Chemotherapy for colorectal cancer (CRC) needs effective yet low-toxicity treatments, and cepharanthine (Cep) shows promise due to its anti-tumor effects.
  • The study investigates how Cep affects mitochondrial function and induces ferroptosis in CRC cells, revealing that it down-regulates TOM20 and TOM70 expression and disrupts the NRF2 signaling pathway, leading to increased oxidative stress and cell death.
  • The findings suggest that targeting TOM proteins and the NRF2 pathway through Cep could provide a new, innovative approach to treating colorectal cancer.
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Article Synopsis
  • Severe endoplasmic reticulum (ER) stress triggers apoptosis in lung cancer, and the study investigates how Cepharanthine (CEP) promotes this process.
  • RNA-sequence analysis revealed that CEP affects gene expression related to ferroptosis and targets NRF2, a key protein in cellular stress response.
  • Experiments showed that CEP induces significant ER stress and ferroptosis in lung cancer cells, leading to increased apoptosis and reduced cancer stemness, highlighting its potential as an effective cancer treatment.
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Pazopanib (PAZ), an oral multi-tyrosine kinase inhibitor, demonstrates promising cytostatic activities against various human cancers. However, its clinical utility is limited by substantial side effects and therapeutic resistance. We developed a nanoplatform capable of delivering PAZ for enhanced anti-breast cancer therapy.

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Chemotherapeutic agents can inhibit the proliferation of malignant cells due to their cytotoxicity, which is limited by collateral damage. Dihydroartemisinin (DHA), has a selective anti-cancer effect, whose target and mechanism remain uncovered. The present work aims to examine the selective inhibitory effect of DHA as well as the mechanisms involved.

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Enhancement of malignant cell immunogenicity to relieve immunosuppression of lung cancer microenvironment is essential in lung cancer treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind of phytopharmaceutical, is effective in inhibiting lung cancer cells and boosting their immunogenicity, while the initial target of DHA's intracellular action is poorly understood. The present in-depth analysis aims to reveal the influence of DHA on the highly expressed TOM70 in the mitochondrial membrane of lung cancer.

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B-Myb has received considerable attention for its critical tumorigenic function of supporting DNA repair. However, its modulatory effects on chemotherapy and immunotherapy have rarely been reported in colorectal cancer. Bortezomib (BTZ) is a novel compound with chemotherapeutic and immunotherapeutic effects, but it fails to work in colorectal cancer with high B-Myb expression.

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Objective: Prompt and effective wound repair is an essential strategy to promote recovery and prevent infection in patients with various types of trauma. Platelets can release a variety of growth factors upon activation to facilitate revascularization and tissue repair, provided that their activation is uncontrollable. The present study is designed to explore the selective activation of platelets by photodynamic and photothermal effects (PDE/PTE) as well as the trauma repair mediated by PDE/PTE.

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Objective: Photodynamic therapy (PDT) primarily treats skin diseases or cancer by generating reactive oxygen species (ROS) to damage cellular DNA, yet drug resistance limits its application. To tackle this problem, the present study was carried out to improve the efficacy of chlorin e6 (Ce6)-PDT using Cepharanthine (CEP) as well as to reveal the potential molecular mechanism.

Materials And Methods: Lewis lung cancer cell line (LLC) was utilized as the cancer cell model.

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Infiltration of tumor-associated macrophages (TAM) characterized by an M2 phenotype is an overriding feature in malignant tumors. Reprogramming TAM is the most cutting-edge strategy for cancer therapy. In the present study, an iron-based metal-organic framework (MOF) nanoreactor loaded with dihydroartemisinin (DHA) is developed, which provides high uptake by TAM and retains their viability, thus effectively addressing the inefficiency of the DHA at low concentrations.

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Dihydroartemisinin (DHA), a natural product derived from the herbal medicine Artemisia annua, is recently used as a novel anti-cancer agent. However, some intrinsic disadvantages limit its potential for clinical management of cancer patients, such as poor water solubility and low bioavailability. Nowadays, the nanoscale drug delivery system emerges as a hopeful platform for improve the anti-cancer treatment.

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Objective: Photodynamic therapy (PDT) may be an effective therapeutic strategy for colorectal cancer at an early stage. However, malignant cells' resistance to photodynamic agents can lead to treatment failure. MYBL2 (B-Myb) is an oncogene in colorectal carcinogenesis and development, for which little research has focused on its effect on drug resistance.

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Background: The immunosuppressive microenvironment of lung cancer serves as an important endogenous contributor to treatment failure. The present study aimed to demonstrate the promotive effect of DHA on immunogenic cell death (ICD) in lung cancer as well as the mechanism.

Methods: The lewis lung cancer cells (LLC), A549 cells and LLC-bearing mice were applied as the lung cancer model.

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In our previous study, target drug delivery and treatment of malignant tumors have been achieved by using platelets as carriers loading nano-chemotherapeutic agents (ND-DOX). However, drug release from ND-DOX-loaded platelets is dependent on negative platelet activation by tumor cells, whose activation is not significant enough for the resulting drug release to take an effective anti-tumor effect. Exploring strategies to proactively manipulate the controlled release of drug-laden platelets is imperative.

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Suppression of the immune microenvironment is an important endogenous contributor to treatment failure in lung cancer. Photodynamic therapy (PDT) is widely used in the treatment of malignant tumors owing to its photo-selectivity and minimal side effects. Some studies have shown the ability of photodynamic action not only to cause photo-cytotoxicity to tumor cells but also to induce immunogenic cell death (ICD).

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Lung cancer recruits tumor-associated macrophages (TAMs) massively, whose predominantly pro-tumor M2 phenotype leads to immunosuppression. Dihydroartemisinin (DHA) has been proven to remodel TAM into an anti-tumor M1 phenotype at certain concentrations in the present study, which was hypothesized to facilitate anti-lung cancer immunotherapy. However, how DHA remodels the TAM phenotype has not yet been uncovered.

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Background: Chemodynamic therapy (CDT) relying on intracellular iron ions and HO is a promising therapeutic strategy due to its tumor selectivity, which is limited by the not enough metal ions or HO supply of tumor microenvironment. Herein, we presented an efficient CDT strategy based on Chinese herbal monomer-dihydroartemisinin (DHA) as a substitute for the HO and recruiter of iron ions to amplify greatly the reactive oxygen species (ROS) generation for synergetic CDT-ferroptosis therapy.

Results: The DHA@MIL-101 nanoreactor was prepared and characterized firstly.

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The present work aims to prove the concept of tumor-targeted drug delivery mediated by platelets. Doxorubicin (DOX) attached to nanodiamonds (ND-DOX) was investigated as the model payload drug of platelets. In vitro experiments first showed that ND-DOX could be loaded in mouse platelets in a dose-dependent manner with a markedly higher efficiency and capacity than free DOX.

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