Photothermal therapy (PTT) has attracted broad attention as a promising method for cancer therapy with less severe side effects than conventional radiation therapy, chemotherapy and surgical ...resection. PTT relies on the photoconversion capacity of photothermal agents (PTAs), and a wide variety of nanomaterials have been employed as PTAs for cancer therapy due to their excellent photothermal properties. The PTAs are systematically or locally administered and become enriched in cancer cells to increase ablation efficiency. In recent years, PTAs and three-dimensional scaffolds have been hybridized to realize the local delivery of PTAs for the repeated ablation of cancer cells. Meanwhile, the composite scaffolds can stimulate the reconstruction and regeneration of the functional tissues and organs after ablation of cancer cells. A variety of composite scaffolds of photothermal nanomaterials have been prepared to combine the advantages of different modalities to maximize their therapeutic efficacy with minimal side effects. The synergistic effects make the composite scaffolds attractive for biomedical applications. This review summarizes these latest advances and discusses the future prospects.
Despite the wide application of radiotherapy in HCC, radiotherapy efficacy is sometimes limited due to radioresistance. Although radioresistance is reported with high glycolysis, the underlying ...mechanism between radioresistance and cancer metabolism, as well as the role of cathepsin H (CTSH) within it, remain unclear. In this study, tumor-bearing models and HCC cell lines were used to observe the effect of CTSH on radioresistance. Proteome mass spectrometry, followed by enrichment analysis, were used to investigate the cascades and targets regulated by CTSH. Technologies such as immunofluorescence co-localization flow cytometry and Western blot were used for further detection and verification. Through these methods, we originally found CTSH knockdown (KD) perturbed aerobic glycolysis and enhanced aerobic respiration, and thus promoted apoptosis through up-regulation and the release of proapoptotic factors such as AIFM1, HTRA2, and DIABLO, consequently reducing radioresistance. We also found that CTSH, together with its regulatory targets (such as PFKL, HK2, LDH, and AIFM1), was correlated with tumorigenesis and poor prognosis. In summary, our study found that the cancer metabolic switch and apoptosis were regulated by CTSH signaling, leading to the occurrence of radioresistance in HCC cells and suggesting the potential value of HCC diagnosis and therapy.
Postsurgical treatment of breast cancer remains a challenge with regard to killing residual cancer cells and regenerating breast defects. To prepare composite scaffolds for postoperative use, gelatin ...is chemically modified with folic acid (FA) and used for hybridization with citrate‐modified Fe3O4 nanoparticles (Fe3O4‐citrate NPs) to fabricate Fe3O4/gelatin composite scaffolds which pore structures are controlled by free ice microparticles. The composite scaffolds have large spherical pores that are interconnected to facilitate cell entry and exit. The FA‐functionalized composite scaffolds have the ability to capture breast cancer cells. The Fe3O4/gelatin composite scaffolds possess a high capacity for magnetic‐thermal conversion to ablate breast cancer cells during alternating magnetic field (AMF) irradiation. In addition, the composite scaffolds facilitate the growth and adipogenesis of mesenchymal stem cells. The composite scaffolds have multiple functions for eradication of residual cancer cells under AMF irradiation and for regeneration of resected adipose tissue when AMF is off.
Bifunctional composite scaffolds of gelatin and Fe3O4 nanoparticles are designed to kill breast cancer cells and promote adipose tissue reconstruction. The composite scaffolds can effectively kill breast cancer cells in vitro and in vivo under alternating magnetic field irradiation. Moreover, the composite scaffolds promote lipid oil droplet formation and up‐regulate the expression of adipogenesis‐related genes when alternating magnetic field is off.
Single nucleotide variants (SNVs) have emerged as increasingly important biomarkers, particularly in the diagnosis and prognosis of cancers. However, most SNVs are rarely detected in blood samples ...from cancer patients as they are surrounded by abundant concomitant wild-type nucleic acids. Herein, we design a system that features a combination of competitive DNA probe system (CDPS) and duplex-specific nuclease (DSN) that we referred to as CAD. A theoretical model was established for the CAD system based on reaction networks. Guided by the theoretical model, we found that a minor loss in sensitivity significantly improved the specificity of the system, thus creating a theoretical discrimination factor (DF) > 100 for most conditions. This non-equivalent tradeoff between sensitivity and specificity provides a new concept for the analysis of rare DNA-sequence variants. As a demonstration of practicality, we applied as-proposed CAD system to identify low variant allele frequency (VAF) in a synthetic template (0.1% VAF) and human genomic DNA (1% VAF). This work promises complete guidance for the design of enzyme-based nucleic acid analysis.
Display omitted
•Combination of competitive DNA probe system and duplex-specific nuclease enable two-layer identification of SNVs.•A theoretical model was established to optimize the performance of CAD System.•This non-equivalent tradeoff between sensitivity and specificity provides a new concept for nucleic acid analysis.•Accurate analysis of low variant allele frequency in human genomic DNA.
Protein arginine methyltransferase 5 (PRMT5) is an epigenetic regulator which has been proven to be a potential target for cancer therapy. We observed that
underwent alternative splicing (AS) and ...generated a spliced isoform
in hepatocellular carcinoma (HCC) patients after radiotherapy. However, the regulatory mechanism and the clinical implications of IR-induced
AS are unclear. This work revealed that serine and arginine rich splicing factor 3 (SRSF3) silencing increased
level, whereas heterogeneous nuclear ribonucleoprotein H 1 (HNRNPH1) silencing reduced it. Then, we found that SRSF3 and HNRNPH1 competitively combined with
pre-mRNA located at the region around the 3'- splicing site on intron 2 and the alternative 3'- splicing site on exon 4. IR-induced SRSF3 downregulation led to an elevated level of
, and exogenous expression of
enhanced cell radiosensitivity. Finally, we confirmed in vivo that IR induced the increased level of
which in turn enhanced tumor killing and regression, and liver-specific Prmt5 depletion reduced hepatic steatosis and delayed tumor progression of spontaneous HCC. In conclusion, our data uncover the competitive antagonistic interaction of SRSF3 and HNRNPH1 in regulating
splicing induced by IR, providing potentially effective radiotherapy by modulating
splicing against HCC.
Systemic lupus erythematosus (SLE) is a latent, insidious autoimmune disease, and with the development of gene sequencing in recent years, our study aims to develop a gene-based predictive model to ...explore the identification of SLE at the genetic level. First, gene expression datasets of SLE whole blood samples were collected from the Gene Expression Omnibus (GEO) database. After the datasets were merged, they were divided into training and validation datasets in the ratio of 7:3, where the SLE samples and healthy samples of the training dataset were 334 and 71, respectively, and the SLE samples and healthy samples of the validation dataset were 143 and 30, respectively. The training dataset was used to build the disease risk prediction model, and the validation dataset was used to verify the model identification ability. We first analyzed differentially expressed genes (DEGs) and then used Lasso and random forest (RF) to screen out six key genes (OAS3, USP18, RTP4, SPATS2L, IFI27 and OAS1), which are essential to distinguish SLE from healthy samples. With six key genes incorporated and five iterations of 10-fold cross-validation performed into the RF model, we finally determined the RF model with optimal mtry. The mean values of area under the curve (AUC) and accuracy of the models were over 0.95. The validation dataset was then used to evaluate the AUC performance and our model had an AUC of 0.948. An external validation dataset (GSE99967) with an AUC of 0.810, an accuracy of 0.836, and a sensitivity of 0.921 was used to assess the model’s performance. The external validation dataset (GSE185047) of all SLE patients yielded an SLE sensitivity of up to 0.954. The final high-throughput RF model had a mean value of AUC over 0.9, again showing good results. In conclusion, we identified key genetic biomarkers and successfully developed a novel disease risk prediction model for SLE that can be used as a new SLE disease risk prediction aid and contribute to the identification of SLE.
Glioblastoma stem cells (GSCs) play a key role in glioblastoma (GBM) resistance to temozolomide (TMZ) chemotherapy. With the increase in research on the tumour microenvironment, exosomes secreted by ...GSCs have become a new focus in GBM research. However, the molecular mechanism by which GSCs affect drug resistance in GBM cells via exosomes remains unclear. Using bioinformatics analysis, we identified the specific expression of ABCB4 in GSCs. Subsequently, we established GSC cell lines and used ultracentrifugation to extract secreted exosomes. We conducted in vitro and in vivo investigations to validate the promoting effect of ABCB4 and ABCB4-containing exosomes on TMZ resistance. Finally, to identify the transcription factors regulating the transcription of ABCB4, we performed luciferase assays and chromatin immunoprecipitation-quantitative PCR. Our results indicated that ABCB4 is highly expressed in GSCs. Moreover, high expression of ABCB4 promoted the resistance of GSCs to TMZ. Our study found that GSCs can also transmit their highly expressed ABCB4 to differentiated glioma cells (DGCs) through exosomes, leading to high expression of ABCB4 in these cells and promoting their resistance to TMZ. Mechanistic studies have shown that the overexpression of ABCB4 in GSCs is mediated by the transcription factor ATF3. In conclusion, our results indicate that GSCs can confer resistance to TMZ in GBM by transmitting ABCB4, which is transcribed by ATF3, through exosomes. This mechanism may lead to drug resistance and recurrence of GBM. These findings contribute to a deeper understanding of the mechanisms underlying drug resistance in GBM and provide novel insights into its treatment.
Exosomes are membrane-bound extracellular vesicles of 40-150 nm in size, that are produced by many cell types, and play an important role in the maintenance of cellular homeostasis. Exosome secretion ...allows for the selective removal of harmful substances from cells. However, it remains unclear whether this process also takes place in glioma cells.
Herein, the role of the tumour-suppressor miR-375 was explored in human glioma cells. Immunoblotting and qRT-PCR experiments demonstrated a functional link between miR-375 and its target, connective tissue growth factor (CTGF), which led to the identification of the underlying molecular pathways. The exosomes secreted by glioma cells were extracted by ultracentrifugation and examined by transmission electron microscopy. Exosomal expression of miR-375 was then analysed by qRT-PCR; while the exosome secretion inhibitor, GW4869, was used to examine the biological significance of miR-375 release. Moreover, the dynamics of miR-375 release by glioma cells was investigated using fluorescently labelled exosomes. Finally, exosomal miR-375 release was examined in an orthotopic xenograft model in nude mice.
MiR-375 expression was downregulated in gliomas. MiR-375 suppressed glioma proliferation, migration, and invasion by inhibiting the CTGF-epidermal growth factor receptor (EGFR) signalling pathway. MiR-375-containing exosomes were also identified in human peripheral blood samples from glioma patients, and their level correlated with disease progression status. Exosomal miR-375 secretion impacted the CTGF-EGFR pathway activity. Once secreted, exosomal miR-375 was not taken back up by glioma cells.
Exosomal miR-375 secretion allowed for sustained activation of the CTGF-EGFR oncogenic pathway, promoting the proliferation and invasion of glioma cells. These findings enhance our understanding of exosome biology and may inspire development of new glioma therapies.
Glioma is a devastating cancer with a dismal prognosis and there is an urgent need to discover novel glioma-specific antigens for glioma therapy. Previous studies have identified CD163-positive ...tumour cells in certain solid tumours, but CD163 expression in glioma remains unknown. In this study, via an analysis of public datasets, we demonstrated that CD163 overexpression in glioma specimens correlated with an unfavourable patient prognosis. CD163 expression was increased in glioma cells, especially primary glioma cells. The loss of CD163 expression inhibited both cell cycle progression and the proliferation of glioblastoma multiforme (GBM) cell lines and primary glioma cells. CD163 interacted directly with casein kinase 2 (CK2) and CD163 silencing reduced AKT/GSK3β/β-catenin/cyclin D1 pathway activity via CK2. Moreover, CD163 was upregulated in CD133-positive glioma stem cells (GSCs), and CD163 downregulation decreased the expression of GSC markers, including CD133, ALDH1A1, NANOG and OCT4. The knockdown of CD163 impaired GSC stemness by inhibiting the CK2/AKT/GSK3β/β-catenin pathway. Finally, a CD163 antibody successfully induced complement-dependent cytotoxicity against glioma cells. Our findings indicate that CD163 contributes to gliomagenesis via CK2 and provides preclinical evidence that CD163 and the CD163 pathway might serve as a therapeutic target for glioma.
Treatment of glioblastoma (GBM) remains very challenging, and it is particularly important to find sensitive and specific molecular targets. In this work, we reveal the relationship between the ...expression of cathepsins and radioresistance in GBM. We analyzed cathepsins (cathepsin B, cathepsin D, cathepsin L, and cathepsin Z/X), which are highly associated with the radioresistance of GBM by regulating different types of cell death. Cathepsins could be potential targets for GBM treatment.
PDF
