Glioblastomas (GBM) are the most frequent brain tumors lacking efficient treatment. The increasingly elucidated gene targets make siRNA-based gene therapy a promising anticancer approach, while an efficient delivery system is urgently needed. Here, polyethyleneimine (PEI)-coated Fe₃O₄ nanoparticles (NPs) have been developed and applied for siRNA delivery into GBM cells to silence repressor element 1-silencing transcription factor (REST). The prepared PEI-coated Fe₃O₄ NPs were characterized as magnetic nanoparticles with a positive charge, by transmission electronic microscopy, dynamic light-scattering analysis and a magnetometer. By gel retardation assay, the nanoparticles were found to form complexes with siRNA and the interaction proportion of NP to siRNA was 2.8:1. The cellular uptake of NP/siRNA complexes was verified by prussian blue staining, fluorescence labeling and flow cytometry in U-87 and U-251 GBM cells. Furthermore, the REST silencing examined by realtime polymerase chain reaction (PCR) and Western blotting presented significant reduction of REST in transcription and translation levels. Upon the treatment of NP/siRNA targeting REST, the GBM cell viabilities were inhibited and the migration capacities were repressed remarkably, analyzed by cell counting kit-8 and transwell assay separately. In this study, we demonstrated the PEI-coated Fe₃O₄ nanoparticle as a vehicle for therapeutic siRNA delivery, at an appropriate NP/siRNA weight ratio for REST silencing in GBM cells, inhibiting cell proliferation and migration efficiently. These might represent a novel potential treatment strategy for GBM.

Exosomes are extracellular vesicles that mediate cell-to-cell communication. Bioactive substances such as DNA, RNA, lipids, and proteins are present in it, and they play an essential role in the pathogenesis of colorectal cancer (CRC). The role of RNA and protein in exosomes has been extensively studied. Exosome DNA has recently attracted the attention of a great deal of scientists. According to studies, exosome DNA mainly contains genomic DNA (gDNA) and mitochondrial DNA (mtDNA), of which exosome gDNA is widely used in liquid biopsy of CRC. It includes a variety of clinically relevant tumor-specific mutation genes. In addition to liquid biopsy, researchers find that exosome gDNA regulates immune and metabolic functions in CRC, making it an important research object. However, the primary research on exosome gDNA is still limited. Here, we describe the occurrence and composition of exosomes. Summarize the essential characteristics and mode of action of exosome gDNA. Remarkably, this paper constitutes a comprehensive summary on the role of exosome gDNA on CRC with the intent of providing a theoretical basis and reference for early diagnosis and clinical treatment of cancer.

In the past 10 years, gene-editing and organoid culture have completely changed the process of biology. Congenital nervous system malformations are difficult to study due to their polygenic pathogenicity, the complexity of cellular and neural regions of the brain, and the dysregulation of specific neurodevelopmental processes in humans. Therefore, the combined application of CRISPR-Cas9 in organoid models may provide a technical platform for studying organ development and congenital diseases. Here, we first summarize the occurrence of congenital neurological malformations and discuss the different modeling methods of congenital nervous system malformations. After that, it focuses on using organoid to model congenital nervous system malformations. Then we summarized the application of CRISPR-Cas9 in the organoid platform to study the pathogenesis and treatment strategies of congenital nervous system malformations and finally looked forward to the future.

Human amnion mesenchymal stem cells (hAMSCs) are promising sources of stem cells in regenerative medicine. The migration stimulated by cytokines is critical for mesenchymal stem cells (MSCs)-based cytotherapy, while the regulatory mechanisms of EGF (epidermal growth factor)-induced hAMSC migration are largely unclear. Here, a novel miRNA N-72 (GenBank accession number: MH269369) has been discovered, and its function on EGF-induced migration in hAMSCs was investigated. High-purity hAMSCs were isolated and cultured in vitro, which were characterized by flow cytometry and trilineage differentiation. The N-72 located on chromosome three was conserved, and pri-N-72 owned the ability to form a stem-loop secondary structure, which was predicated by bioinformatic programs. The expression of mature N-72 was verified in several human cells including hAMSC by real-time PCR. In EGF-stimulated hAMSC, N-72 showed a significant reduction in a PI3K and p38 MAPK-dependent manner, and N-72 mimics transfection-inhibited EGF-induced migration, which was verified by scratch assay and transwell assay. Further, the predicated target gene MMP2 was proved to be a direct target of N-72 via luciferase reporter assay, real-time PCR, and Western blotting. The results that MMP2 silencing repressed hAMSC migration suggested MMP2 as a functional downstream target of N-72. In summary, we have discovered the novel N-72, and it was crucial for EGF-induced migration by targeting MMP2 in hAMSCs.

Colorectal cancer (CRC) is one of the most common malignant tumors with a high lethal rate globally, and novel strategies for its prevention and therapy are urgently needed. In our previous work, 8-methoxyflindersine (8-MF), a quinoline alkaloid, was isolated from the Dictamni cortex, and its bioactivities were largely unknown. In this study, we found that 8-MF significantly inhibited cell viability in the CRC cell lines LoVo and RKO. The 8-MF-induced CRC cell apoptosis, as well as cell cycle disorder, were further verified by cyclins dysregulation in mRNA and protein levels. Further, the activation of MAPK family members p38 and ERK1/2 was observed after 8-MF treatment. Moreover, the protein–protein interaction of 8-MF with cyclins and MAPKs was demonstrated using the STRING database. The 8-MF could bind to p38 and ERK1/2 proteins in molecular docking. Taken together, we found that 8-MF induced apoptosis and cell cycle disorder involving MAPK signaling activation in CRC cells, indicating 8-MF as a novel lead compound candidate for the development of anti-tumor drugs for CRC.

The heterogeneity of tumor cells facilitates their dynamic adaptation to tumor microenvironmental pressures throughout progression. Nevertheless, the mechanisms underlying intercellular communication and transformation among heterogeneous tumor cells remain inadequately understood. In this study, we indicate that Ephrin type-A receptor 2 (EphA2) is heterogeneously expressed in gastric cancer (GC) tumor cells, with those exhibiting elevated EphA2 (EphA2^High) expression demonstrating enhanced migratory and invasive capabilities. EphA2^High cells facilitate the transfer of EphA2 via exosomes, which subsequently localize on the membrane of EphA2^Low cells, thereby activating the ERK signaling pathway in a ligand-independent manner. This process promotes the transformation of EphA2^Low cells and contributes to the progression of GC. An investigation into the correlation between serum levels and tumor metastasis in patients with GC revealed that those with lymph node metastasis exhibited higher levels of serum exosomal EphA2. This study elucidates the process of dominant group formation within heterogeneous tumor cells and suggests the viability of exosomal EphA2 as a potential biomarker for further clinical investigation.