Cathepsin B: The dawn of tumor therapy.

Cathepsin B (CTSB) is a key lysosomal protease that plays a crucial role in the development of cancer. This article elucidates the relationship between CTSB and cancer from the perspectives of its structure, function, and role in tumor growth, migration, invasion, metastasis, angiogenesis and autophagy. Further, we summarized the research progress of cancer treatment related drugs targeting CTSB, as well as the potential and advantages of Traditional Chinese medicine in treating tumors by regulating the expression of CTSB.

Ononin promotes radiosensitivity in lung cancer by inhibiting HIF-1α/VEGF pathway.

BACKGROUND: In our previous study, we provided evidence that Astragalus mongholicus Bunge(AM) and its extracts possess a protective capability against radiation-induced damage, potentially mediated through the reduction of reactive oxygen species (ROS) and nitric oxide (NO). However, we were pleasantly surprised to discover during our experimentation that AM not only offers protection against radiation damage but also exhibits a radiation sensitization effect. This effect may be attributed to a specific small molecule present in AM known as ononin. Currently, radiation sensitizers are predominantly found in nitrazole drugs and nanomaterials, with no existing reports on the radiation sensitization properties of ononin, nor its underlying mechanism. PURPOSE: This study aims to investigate the sensitization effect of the small molecule ononin derived from AM on lung cancer radiotherapy, elucidating its specific molecular mechanism of action. Additionally, the safety profile of combining astragalus small molecule ononin with radiation therapy will be evaluated. METHODS: The effective concentration of ononin was determined through cell survival experiments, and the impact of ononin combined with varying doses of radiation on lung cancer cells was observed using CCK-8 and cell cloning experiments. The apoptotic effect of ononin combined with radiation on lung cancer cells was assessed using Hochester staining, flow cytometry, and WB assay. Additionally, WB and immunofluorescence analysis were conducted to investigate the influence of ononin on HIF-1α/VEGF pathway. Furthermore, Molecular Dynamics Simulation was employed to validate the targeted binding ability of ononin and HIF-1α. A lung cancer cell line was established to investigate the effects of knockdown and overexpression of HIF-1α. Subsequently, the experiment was repeated using tumor bearing nude mice and C57BL/6 mouse models in an in vivo study. Tumor volume was measured using a vernier caliper, while HE, immunohistochemistry, and immunofluorescence techniques were employed to observe the effects of ononin combined with radiation on tumor morphology, proliferation, and apoptosis. Additionally, Immunofluorescence was employed to examine the impact of ononin on HIF-1α/VEGF pathway in vivo, and its effect on liver function in mice was assessed through biochemistry analysis. RESULTS: At a concentration of 25 µM, ononin did not affect the proliferation of lung epithelial cells but inhibited the survival of lung cancer cells. In vitro experiments demonstrated that the combination of ononin and radiation could effectively inhibit the growth of lung cancer cells, induce apoptosis, and suppress the excessive activation of the Hypoxia inducible factor 1 alpha/Vascular endothelial growth factor pathway. In vivo experiments showed that the combination of ononin and radiation reduced the size and proliferation of lung cancer tumors, promoted cancer cell apoptosis, mitigated abnormal activation of the Hypoxia inducible factor 1 alpha pathway, and protected against liver function damage. CONCLUSION: This study provides evidence that the combination of AM and its small molecule ononin can enhance the sensitivity of lung cancer to radiation. Additionally, it has been observed that this combination can specifically target HIF-1α and exert its effects. Notably, ononin exhibits the unique ability to protect liver function from damage while simultaneously enhancing the tumor-killing effects of radiation, thereby demonstrating a synergistic and detoxifying role in tumor radiotherapy. These findings contribute to the establishment of a solid basis for the development of novel radiation sensitizers derived from traditional Chinese medicine.

Energy metabolism: A critical target of cardiovascular injury.

Cardiovascular diseases are the main killers threatening human health. Many studies have shown that abnormal energy metabolism plays a key role in the occurrence and development of acute and chronic cardiovascular diseases. Regulating cardiac energy metabolism is a frontier topic in the treatment of cardiovascular diseases. However, we are not very clear about the choice of different substrates, the specific mechanism of energy metabolism participating in the course of cardiovascular disease, and how to develop appropriate drugs to regulate energy metabolism to treat cardiovascular disease. Therefore, this paper reviews how energy metabolism participates in cardiovascular pathophysiological processes and potential drugs aimed at interfering energy metabolism.It is expected to provide good suggestions for promoting the clinical prevention and treatment of cardiovascular diseases from the perspective of energy metabolism.

Research progress on pharmacological effects and mechanisms of cepharanthine and its derivatives.

Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid compound found in plants of the Stephania genus, which has biological functions such as regulating autophagy, inhibiting inflammation, oxidative stress, and apoptosis. It is often used for the treatment of inflammatory diseases, viral infections, cancer, and immune disorders and has great clinical translational value. However, there is no detailed research on its specific mechanism and dosage and administration methods, especially clinical research is limited. In recent years, CEP has shown significant effects in the prevention and treatment of COVID-19, suggesting its potential medicinal value waiting to be discovered. In this article, we comprehensively introduce the molecular structure of CEP and its derivatives, describe in detail the pharmacological mechanisms of CEP in various diseases, and discuss how to chemically modify and design CEP to improve its bioavailability. In summary, this work will provide a reference for further research and clinical application of CEP.

Review: Mechanisms and perspective treatment of radioresistance in non-small cell lung cancer.

Radiotherapy is the major treatment of non-small cell lung cancer (NSCLC). The radioresistance and toxicity are the main obstacles that leading to therapeutic failure and poor prognosis. Oncogenic mutation, cancer stem cells (CSCs), tumor hypoxia, DNA damage repair, epithelial-mesenchymal transition (EMT), and tumor microenvironment (TME) may dominate the occurrence of radioresistance at different stages of radiotherapy. Chemotherapy drugs, targeted drugs, and immune checkpoint inhibitors are combined with radiotherapy to treat NSCLC to improve the efficacy. This article reviews the potential mechanism of radioresistance in NSCLC, and discusses the current drug research to overcome radioresistance and the advantages of Traditional Chinese medicine (TCM) in improving the efficacy and reducing the toxicity of radiotherapy.