Background: Osteosarcoma (OS) is one of the most common aggressive bone malignancy tumors in adolescents. With the application of new chemotherapy regimens, finding new and effective anti-OS drugs to coordinate program implementation is urgent for the patients of OS. Oridonin had been proved to mediate anti-tumor effect on OS cells, but its mechanism has not been fully elucidated. Methods: The effects of oridonin on the viability, clonal formation and migration of 143B and U2OS cells were detected by CCK-8, colony formation assays and wound-healing test. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to explore the mechanism of oridonin on OS. Western blot (WB), real-time quantitative PCR (qRT-PCR) were used to detect the expression levels of apoptosis and ferroptosis-relative proteins and genes. Annexin V-FITC apoptosis detection kit and flow cytometry examination were used to detect the level of apoptosis. Iron assay kit was used to evaluate the relative Fe²⁺ content. The levels of mitochondrial membrane potential and lipid peroxidation production was determined by mitochondrial membrane potential detection kit and ROS assay kit. Results: Oridonin could effectively inhibit the survival, clonal formation and metastasis of OS cells. The KEGG results indicated that oridonin is associated with the malignant phenotypic signaling pathways of proliferation, migration, and drug resistance in OS. Oridonin was capable of inhibiting expressions of BAX, cl-caspase3, SLC7A11, GPX4 and FTH1 proteins and mRNA, while promoting the expressions of Bcl-2 and ACSL4 in 143B and U2OS cells. Additionally, we found that oridonin could promote the accumulation of reactive oxygen species (ROS) and Fe²⁺ in OS cells, as well as reduce mitochondrial membrane potential, and these effects could be significantly reversed by the ferroptosis inhibitor ferrostatin-1 (Fer-1). Conclusion: Oridonin can trigger apoptosis and ferroptosis collaboratively in OS cells, making it a promising and effective agent for OS therapy.

Antibody decorated nanoparticles with brightly red emissions are promising probes for targeted detection of cancer cells due to their excellent specificity, deep penetration depth, high photostability and low phototoxicity. Nevertheless, traditional fluorophores with planar structures and a strong donor–acceptor (D–A) effect are not ideal candidates for preparing the targeting nanoprobes since the aggregation of these fluorophores may cause the quenching of the emission due to the strong intermolecular interactions. Herein, a new red emissive luminogen with aggregation-induced emission property has been designed and synthesized. The new AIE luminogen with a conjugated D–A structure not only avoids the quenching of fluorescence but also shows enhanced photostability and remarkable two-photon absorption in its nanoaggregates. Encapsulated by biocompatible DSPE-PEG₂₀₀₀ and DSPE-PEG₂₀₀₀-COOH, these AIE nanoparticles can be conjugated with antibody cetuximab with targeting specificity to the epidermal growth factor receptor (EGFR), which is generally overexpressed in non-small lung cancer cells. These AIEgen nanoparticles provide an ideal architecture for cancer cell-specific fluorescence imaging and detection with bright red emission, high photostability, and good specificity.

The clinical manifestations of bone metastases are diversified while many sites remain asymptomatic at early stage. As the early diagnosis method is not perfect and the early symptoms of tumor bone metastasis are not typical, bone metastasis is not easy to be detected. Therefore, the search for bone metastasis-related markers is effective for timely detection of tumor bone metastases and the development of drugs to inhibit bone metastases. As a result, bone metastases can only be diagnosed when symptoms are found, increasing the risk of developing skeletal-related event (SREs), which significantly impairs the patient’s quality of life. Therefore, the early diagnosis of bone metastases is of great importance for the treatment and prognosis of cancer patients. Changes of bone metabolism indexes appear earlier in bone metastases, but the traditional biochemical indexes of bone metabolism lack of specificity and could be interfered by many factors, which limits their application in the study of bone metastases. Some new biomarkers of bone metastases have good diagnostic value, such as proteins, ncRNAs, circulating tumor cells (CTCs). Therefore, this study mainly reviewed the initial diagnostic biomarkers of bone metastases which were expected to provide references for the early detection of bone metastases.

Novel Insights into the Stemness and Immune Privilege of Mesenchymal Stem Cells from Human Wharton Jelly by Single-Cell RNA Sequencing - Article abstract #934660

The article reports a mitochondrial targeting AIEgens, TPE-PDT, demonstrating exceptional targeting accuracy, minimal cellular harm, and superior photostability under two-photon excitation, which enhances the effectiveness of photodynamic therapy.