Crosstalk within and beyond the Polycomb repressive system.

The development of multicellular organisms depends on spatiotemporally controlled differentiation of numerous cell types and their maintenance. To generate such diversity based on the invariant genetic information stored in DNA, epigenetic mechanisms, which are heritable changes in gene function that do not involve alterations to the underlying DNA sequence, are required to establish and maintain unique gene expression programs. Polycomb repressive complexes represent a paradigm of epigenetic regulation of developmentally regulated genes, and the roles of these complexes as well as the epigenetic marks they deposit, namely H3K27me3 and H2AK119ub, have been extensively studied. However, an emerging theme from recent studies is that not only the autonomous functions of the Polycomb repressive system, but also crosstalks of Polycomb with other epigenetic modifications, are important for gene regulation. In this review, we summarize how these crosstalk mechanisms have improved our understanding of Polycomb biology and how such knowledge could help with the design of cancer treatments that target the dysregulated epigenome.

Toxicological sensitivity of protozoa to pesticides and nanomaterials: A prospect review.

Protozoa are sensitive indicators of pollutant toxicity. This review presents and discusses the toxicological studies of protozoa and the toxicological conventional test species (Daphnia magna) by pesticides and nanomaterials, particularly comparing the sensitivity of through relative tolerance analysis, Z-score, and species sensitivity index. The sensitivity of different species of protozoa varies greatly. The protozoa Paramecium sp. and Tetrahymena sp. are not sensitive species; conversely, Urostyla sp. is sensitive to dimethoate and nanomaterials Ag-NPs, respectively ZnO-NPs, and CuO-NPs, fits the use as an indicator species on these substances. The prospects to explore scientific toxicity exposure protocols, expand the protozoan species examined, and screen the sensitive species under the protocols are discussed. This prospect review advances the knowledge for including the sensitive protozoa as an indicator species in comprehensive toxicological analysis for pesticides and nanomaterials.

Multi-omics clustering for cancer subtyping based on latent subspace learning.

The increased availability of high-throughput technologies has enabled biomedical researchers to learn about disease etiology across multiple omics layers, which shows promise for improving cancer subtype identification. Many computational methods have been developed to perform clustering on multi-omics data, however, only a few of them are applicable for partial multi-omics in which some samples lack data in some types of omics. In this study, we propose a novel multi-omics clustering method based on latent sub-space learning (MCLS), which can deal with the missing multi-omics for clustering. We utilize the data with complete omics to construct a latent subspace using PCA-based feature extraction and singular value decomposition (SVD). The data with incomplete multi-omics are then projected to the latent subspace, and spectral clustering is performed to find the clusters. The proposed MCLS method is evaluated on seven different cancer datasets on three levels of omics in both full and partial cases compared to several state-of-the-art methods. The experimental results show that the proposed MCLS method is more efficient and effective than the compared methods for cancer subtype identification in multi-omics data analysis, which provides important references to a comprehensive understanding of cancer and biological mechanisms. AVAILABILITY: The proposed method can be freely accessible at https://github.com/ShangCS/MCLS.

Interactive gene identification for cancer subtyping based on multi-omics clustering.

Recent advances in multi-omics databases offer the opportunity to explore complex systems of cancers across hierarchical biological levels. Some methods have been proposed to identify the genes that play a vital role in disease development by integrating multi-omics. However, the existing methods identify the related genes separately, neglecting the gene interactions that are related to the multigenic disease. In this study, we develop a learning framework to identify the interactive genes based on multi-omics data including gene expression. Firstly, we integrate different omics based on their similarities and apply spectral clustering for cancer subtype identification. Then, a gene co-expression network is construct for each cancer subtype. Finally, we detect the interactive genes in the co-expression network by learning the dense subgraphs based on the L1 prosperities of eigenvectors in the modularity matrix. We apply the proposed learning framework on a multi-omics cancer dataset to identify the interactive genes for each cancer subtype. The detected genes are examined by DAVID and KEGG tools for systematic gene ontology enrichment analysis. The analysis results show that the detected genes have relationships to cancer development and the genes in different cancer subtypes are related to different biological processes and pathways, which are expected to yield important references for understanding tumor heterogeneity and improving patient survival.

Enhanced treatment effect of nanoparticles containing cisplatin and a GSH-reactive probe compound.

Cisplatin is a highly effective antitumor drug, which can kill cancer cells by crossing-linking DNA and inhibiting transcription, but this process is limited by the combination of cisplatin and many endogenous nucleophiles, such as glutathione (GSH). Thus, when cisplatin enter cells, it is potentially vulnerable to cytoplasmic inactivation by GSH. To settle this bottleneck, we designed and synthesized a probe compound (Probe 1) and fabricated pH-responsed cisplatin, Probe 1-loaded lipid-polymer hybrid NanoParticles (CPNPs) using a single-step sonication method. Probe 1 can specifically bind to GSH, thus avoiding the combination of GSH and cisplatin, and enhancing the pharmacological activity of cisplatin. In vitro studies have suggested CPNPs, compared with cisplatin, loaded lipid-polymer hybrid NanoParticles CNPs (Not contain Probe 1), could efficiently kill MCF-7 human breast cancer cells and A549 human nonsmall lung cancer cell. Hence, the CPNPs provided a new idea for treating cancer.

Mesoporous silica-coated gold nanoframes as drug delivery system for remotely controllable chemo-photothermal combination therapy.

Tumor cells experience higher chemotherapy stress under condition of elevated temperature. As a result, developing novel nanoagents that integrates chemotherapy and thermotherapy holds great promise in biomedicine. Herein, utilizing spatially confined galvanic replacement method, we fabricated a yolk-shell Au@mSiO2 nanoframes with Au NPs and mesoporous silica as yolk and shell, respectively, to sever as an excellent drug nanocarrier with effective photothermal conversion efficiency. Taking full advantage of the high temperature response of the Au@mSiO2 nanoframes, the phase change material 1-tetradecanol (TD) was creatively employed as gatekeepers, intelligently controlling the release of loaded agents. Then, the actively targeted Alanine-Alanine-Asparagine, legumain-recognizable oligopeptides was decorated on the surface of the prepared nanoframes. Upon exposure to near-infrared light, the GC-PtAu@mSiO2-TD nanoframes not only exhibited a high localized temperature response, but also triggered the quick release of loaded cargos, and thus improved the chemotherapeutic efficacy. The in vitro cytotoxicity studies indicated the remarkable synergistic effects. Meanwhile, the laser confocal studies and flow cytometry showed the oligopeptides facilitated the intracellular uptake of GC-PtAu@mSiO2-TD nanoframes in MGC-803 cells. Our study highlighted the great potential of the GC-PtAu@mSiO2-TD nanoframes in drug delivery and the combination of chemotherapy and photothermal therapy.

Overexpression of CDCA7 predicts poor prognosis and induces EZH2-mediated progression of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with high proliferative and metastatic phenotypes. CDCA7, a new member of the cell division cycle associated family of genes, is involved in embryonic development and dysregulated in various types of human cancer. However, the biological role and molecular mechanism of CDCA7 in TNBC have not been defined. Herein, we found that CDCA7 was preferentially and markedly expressed in TNBC cell lines and tissues. High expression of CDCA7 was associated with metastatic relapse status and predicted poorer disease-free survival in patients with TNBC. We observed that CDCA7 silencing in TNBC cell lines effectively impaired cell proliferation, invasion and migration in vitro. Importantly, depletion of CDCA7 strongly reduced the tumorigenicity and distant colonization capacities of TNBC cells in vivo. Furthermore, CDCA7 increased the expression of EZH2, a marker of aggressive breast cancer that is involved in tumor progression, by enhancing the transcriptional activity of its promoter. This increase in EZH2 expression was essential for the CDCA7-mediated effects on TNBC progression. Finally, our immunohistochemical analysis revealed that the CDCA7/EZH2 axis was clinical relevant. These findings suggest CDCA7 plays a crucial role in TNBC progression by transcriptionally upregulating EZH2 and might be a potential prognostic factor and therapeutic target in TNBC.

Folate-decorated and NIR-activated nanoparticles based on platinum(IV) prodrugs for targeted therapy of ovarian cancer.

Platinum-based drugs are used to treat a variety of cancers but have many side effects such as nephrotoxicity and neurotoxicity. A folate-decorated nanoparticles system with a good drug payload can selectively deliver drugs into folate receptor (FR)-overexpressing cancer cells to prevent the shortcomings of platinum-based chemotherapy. Here, folate-decorated and near-infrared (NIR) laser-activated nanoparticles (abbreviated as PtIV-FINPs) were prepared via ultrasonic self-assembling of platinum(IV) prodrug c,c,t-Pt(NH3)2Cl2(OOCCH2CH2COOH)2, folic acid (FA)-functionalized lipid DSPE-PEG-FA and NIR fluorescent dye indocyanine green (ICG). The obtained PtIV-FINPs had almost spherical shape with a mean diameter about 100 nm. In vitro cellular uptake, cytotoxicity assays revealed that upon NIR irradiation, PtIV-FINPs further enhanced cellular uptake and generated higher cytotoxicity against human ovarian carcinoma SKOV3 cells than non-targeted or non-NIR activated nanoparticles. Thus, the multifunctional nanoparticles have potential to be developed as an attractive drug delivery system for effective chemotherapy against FR-overexpressing cells.

Folate-modified, indocyanine green-loaded lipid-polymer hybrid nanoparticles for targeted delivery of cisplatin.

Cisplatin is a potent antitumor drug, which is widely applied in clinical cancer treatment. However, cisplatin can hardly distinguish between healthy tissue and tumor tissue, resulting in serious toxic side effects. Indocyanine green (ICG) is a FDA-approved near-infrared (NIR) fluorescence dye which has been used in photothermal therapy and optically mediated diagnostic, but the application of ICG is limited by its concentration-dependent aggregation, poor aqueous stability in vitro, lack of target specificity and rapid elimination from the body. Herein, to overcome these limitations of cisplatin and ICG, we fabricated folate-modified, cisplatin, ICG-loaded lipid-polymer hybrid nanoparticles (FCINPs) using a single-step sonication method. The FCINPs exhibited well-defined monodispersity, significant stability and excellent NIR penetration ability. The intracellular uptake experiment showed that the targeting efficacy of the FCINPs was more effective in folate receptors (FRs) over-expressing MCF-7 cells than FRs negative A549 cells. In addition, compared with chemo or photothermal treatment alone, the treatment of FCINPs in combination with 808 nm NIR laser irradiation can significantly induce the apoptosis and necrosis of MCF-7 cells. These findings indicated that the FCINPs would be a promising nanosized drug formulation for tumor-targeted therapy in the future.

A strategy for photothermal conversion of polymeric nanoparticles by polyaniline for smart control of targeted drug delivery.

The near-infrared (NIR)-mediated novel strategy to control the drug release from nanocarriers has developed rapidly in recent decades. Polyaniline as a non-cytotoxic and electroactive material for studying cellular proliferation has attracted great attention in recent years. In the present work, polyaniline-mediated polymeric nanoparticles were developed to target the delivery of cisplatin and release it in a controllable way. The prepared polyaniline nanoparticles displayed a size of 90 ± 1.0 nm, a favorable morphology in water, and could be targeted to tumors through the high affinity between trastuzumab and the overexpressed Her2 in tumor cells. In addition, the developed nanoparticles demonstrated exciting photothermal conversion efficiency induced by NIR light and achieved significant cell inhibition efficiency (93.97%) in vitro when exposed to an 808 nm NIR laser with the power of 1.54 W for 5 min. Therefore, the developed external control release delivery system with excellent specificity and high cytotoxicity exhibited great potential in cell research and our research demonstrated that the polyaniline also has potential in the application of photothermal conversion in biomedicine.

Enhanced legumain-recognition and NIR controlled released of cisplatin-indocyanine nanosphere against gastric carcinoma.

Cisplatin-therapy has faced limitations in the gastric cancer therapy. To settle the bottleneck, enhanced specificity and controlled-release property are choosen. We synthesize cisplatin and indocyanine green (ICG) loaded PLGA-(DSPE-PEG2000) nanoparticles, which is abbreviated as CINPs. And we conjugate the Gly-Cys-Gly-Ala-Ala-Asn-Leu (GCGAANL) heptapeptide upon the surface of CINPs, the product is abbreviated as ACINPs. ACINPs with nearly 110nm exhibit good monodispersity and size stability. The EE (efficiency of encapsulation) and LE (loading of encapsulation) of cisplatin loaded into ACINPs are optimized as 29.81% and 3.88%. MGC803 cells overexpressing the legumain and MKN28 cells, which negatively express the legumain as well as the normal stomach cells, are selected. In vitro studies have suggested ACINPs, compared with CINPs, could be recognized by MGC803 cells and efficiently killed the cancer cells, while be harmless to MKN28 cells, which indicates the specificity and safety of ACINPs. Under irradiation of 808nm NIR irradiation, ICG loaded in ACINPs could rapidly transform the light to heat up to 60℃. Nanoparticles compared with non-irraditaion group could be quickly disrupted and release the cisplatin which could enhance the controlled-release ability. Hence, the ACINPs exhibit great potential in avoiding the side effects and enhancing the therapy ability of cisplatin.