Nuclear p62 condensates stabilize the promyelocytic leukemia nuclear bodies by sequestering their ubiquitin ligase RNF4.

Liquid-liquid phase separation has emerged as a crucial mechanism driving the formation of membraneless biomolecular condensates, which play important roles in numerous cellular processes. These condensates, found both in the nucleus and cytoplasm, are formed through multivalent, low-affinity interactions between various molecules. P62-containing condensates serve, among other functions, as proteolytic hubs for the ubiquitin-proteasome system.

A Magnetically and Electrically Powered Hybrid Micromotor in Conductive Solutions: Synergistic Propulsion Effects and Label-Free Cargo Transport and Sensing.

Electrically powered micro- and nanomotors are promising tools for in vitro single-cell analysis. In particular, single cells can be trapped, transported, and electroporated by a Janus particle (JP) using an externally applied electric field. However, while dielectrophoretic (DEP)-based cargo manipulation can be achieved at high-solution conductivity, electrical propulsion of these micromotors becomes ineffective at solution conductivities exceeding ≈0.

High Expression of G6PD Increases Doxorubicin Resistance in Triple Negative Breast Cancer Cells by Maintaining GSH Level.

Resistance to doxorubicin (DOX) remains a big challenge to breast cancer treatment especially for triple negative breast cancer (TNBC). Our previous study revealed that the antioxidant system plays an important role in conferring metastasis derived DOX resistance. In this study, we used two-dimensional difference gel electrophoresis (2D-DIGE) proteomics to compare the expression profiles of two generations of TNBC cell lines which have increased metastatic ability in nude mice and exhibited resistance to DOX.

How multi-component cascades operate in cells: lessons from the ubiquitin system-containing liquid-separated condensates.

Membraneless condensates have recently caught the attention of biologists as hubs for cellular components required for catalysis of basic processes. Whether they are real has become the center of heated discussion where the main issues are their mechanism of assembly and function. A recent study describing these condensates as hubs for protein degradation by the ubiquitin system may shed a new light on this recent development in cell biology.

Micromotor-based localized electroporation and gene transfection of mammalian cells.

Herein, we studied localized electroporation and gene transfection of mammalian cells using a metallodielectric hybrid micromotor that is magnetically and electrically powered. Much like nanochannel-based, local electroporation of single cells, the presented micromotor was expected to increase reversible electroporation yield, relative to standard electroporation, as only a small portion of the cell's membrane (in contact with the micromotor) is affected. In contrast to methods in which the entire membrane of all cells within the sample are electroporated, the presented micromotor can perform, via magnetic steering, localized, spatially precise electroporation of the target cells that it traps and transports.

Correction: Non-toxic dose of liposomal honokiol suppresses metastasis of hepatocellular carcinoma through destabilizing EGFR and inhibiting the downstream pathways.

[This corrects the article DOI: 10.18632/oncotarget.13687.

Active Particle Based Selective Transport and Release of Cell Organelles and Mechanical Probing of a Single Nucleus.

Self-propelling micromotors are emerging as a promising microscale tool for single-cell analysis. The authors have recently shown that the field gradients necessary to manipulate matter via dielectrophoresis can be induced at the surface of a polarizable active ("self-propelling") metallo-dielectric Janus particle (JP) under an externally applied electric field, acting essentially as a mobile floating microelectrode. Here, the application of the mobile floating microelectrode to trap and transport cell organelles in a selective and releasable manner is successfully extended.

Active particles as mobile microelectrodes for selective bacteria electroporation and transport.

Self-propelling micromotors are emerging as a promising micro- and nanoscale tool for single-cell analysis. We have recently shown that the field gradients necessary to manipulate matter via dielectrophoresis can be induced at the surface of a polarizable active ("self-propelling") metallodielectric Janus particle (JP) under an externally applied electric field, acting essentially as a mobile floating microelectrode. Here, we successfully demonstrated that the application of an external electric field can singularly trap and transport bacteria and can selectively electroporate the trapped bacteria.

Graphene quantum dot based charge-reversal nanomaterial for nucleus-targeted drug delivery and efficiency controllable photodynamic therapy.

Graphene quantum dots (GQDs), the new zero-dimensional carbon nanomaterial, have been demonstrated as a promising material for biomedical applications due to its good biocompatibility and low toxicity. However, the integration of multiple therapeutic approaches into a nanosized platform based on the GQD has not been explored yet to our best knowledge. In this report, we regulate the generation of reactive oxygen species (ROS) when using the GQD as a photosensitizer by varying the doping amount of nitrogen atoms to achieve efficiency controllable photodynamic therapy.

MnSOD mediates shear stress-promoted tumor cell migration and adhesion.

Circulation of cancer cells in the bloodstream is a vital step for distant metastasis, during which cancer cells are exposed to hemodynamic shear stress (SS). The actions of SS on tumor cells are complicated and not fully understood. We previously reported that fluidic SS was able to promote migration of breast cancer cells by elevating the cellular ROS level.

Rapid identification of antimicrometastases drugs using integrated model systems with two dimensional monolayer, three dimensional spheroids, and zebrafish xenotransplantation tumors.

Treating systemic metastases at the micrometastatic stage is a potential strategy to inhibit cancer metastasis. This study aims to establish an apoptosis sensor-based platform for rapid, effective, and noninvasive identification of drugs that can inhibit the proliferation of micrometastatic cancer cells. We stably transfected the plasmid DNA encoding the fluorescence resonance energy transfer-based caspase-3 sensor into highly metastatic melanoma B16F10 cells.

Extracellular Vesicle Directed Exogenous Ion Channel Transport for Precise Manipulation of Biological Events.

A larger number of human diseases are related to dysregulation or loss of cellular functions. Effective restoration of the missing or defective cellular functions is highly desirable for fundamental research and therapeutic applications. Inspired by the fantastic feature of cell-derived extracellular vesicles (EVs) that can transport various bioactive molecules between cells, herein, we developed a simple and efficient strategy based on EVs for transferring ion channels to recipient cells, thereby conferring specific biological function to the target cells and regulating the biological events.

High Shear Stresses under Exercise Condition Destroy Circulating Tumor Cells in a Microfluidic System.

Circulating tumor cells (CTCs) are the primary targets of cancer treatment as they cause distal metastasis. However, how CTCs response to exercise-induced high shear stress is largely unknown. To study the effects of hemodynamic microenvironment on CTCs, we designed a microfluidic circulatory system that produces exercise relevant shear stresses.

Hemodynamic shear stress stimulates migration and extravasation of tumor cells by elevating cellular oxidative level.

Cancer cells are shed into the blood stream and are exposed to hemodynamic shear stress during metastasis. It has been shown that shear stress can destroy circulating tumor cells (CTCs) both in vitro and in vivo. However, it remains unclear whether shear stress can modulate the properties and functions of tumor cells in a manner that might help CTCs to exit circulation.

Non-toxic dose of liposomal honokiol suppresses metastasis of hepatocellular carcinoma through destabilizing EGFR and inhibiting the downstream pathways.

At present, there is no specific anti-metastasis drug in HCC treatment. Drugs used for primary HCC tumors and tumor metastasis are very similar, among which cytotoxic drugs are prevalent, such as cisplatin, doxorubicin and 5-FU. The EGFR pathway plays an important role in promoting hepatocellular carcinoma (HCC) metastasis.

High expression of MnSOD promotes survival of circulating breast cancer cells and increases their resistance to doxorubicin.

Understanding the survival mechanism of metastatic cancer cells in circulation will provide new perspectives on metastasis prevention and also shed new light on metastasis-derived drug resistance. In this study, we made it feasible to detect apoptosis of circulating tumor cells (CTCs) in real-time by integrating a fluorescence resonance energy transfer (FRET)-based caspase sensor into one in vitro microfluidic circulatory system, and two in vivo models: zebrafish circulation and mouse lung metastatic model. Our study demonstrated that fluid shear stresses triggered apoptosis of breast cancer cells in circulation by elevating the mitochondrial production of the primary free radical, superoxide anion.

Physical supports from liver cancer cells are essential for differentiation and remodeling of endothelial cells in a HepG2-HUVEC co-culture model.

Blood vessel remodeling is crucial in tumor growth. Growth factors released by tumor cells and endothelium-extracellular matrix interactions are highlighted in tumor angiogenesis, however the physical tumor-endothelium interactions are highly neglected. Here, we report that the physical supports from hepatocellular carcinoma, HepG2 cells, are essential for the differentiation and remodeling of endothelial cells.

Application of a fluorescence resonance energy transfer (FRET)-based biosensor for detection of drug-induced apoptosis in a 3D breast tumor model.

Two-dimensional (2D) cultures are commonly used for testing drug effects largely because of their easy maintenance. But they do not represent the spatial interactions of the cells within a tumor. Three-dimensional (3D) cultures can overcome those limitations thus mimicking the architecture of solid tumor.

Tracking mesenchymal stem cell tumor-homing using fluorescent silica nanoparticles.

Stem cell tracking can reveal the underlying biological processes of stem-cell-based therapies such as the migration and biodistribution of human mesenchymal stem cells (hMSCs) in cancer therapy. Nanoparticle-based contrast agents offer unprecedented opportunities for achieving this goal due to their unique and tunable imaging capabilities. However, most nanoparticles are still in the process of development due to challenges such as retention time and safety issues, and are inaccessible to most researchers.

Cytotoxic and apoptotic effects of constituents from Millettia pachycarpa Benth.

The aim of this study is to investigate the cytotoxic and apoptotic effects of constituents from the seeds of Millettia pachycarpa Benth. Fourteen compounds (1-14) including one novel chalcone (10) were isolated as active principles from Chinese herbal medicine M. pachycarpa Benth.

A high-throughput fluorescence resonance energy transfer (FRET)-based endothelial cell apoptosis assay and its application for screening vascular disrupting agents.

In this study, we developed a high-throughput endothelial cell apoptosis assay using a fluorescence resonance energy transfer (FRET)-based biosensor. After exposure to apoptotic inducer UV-irradiation or anticancer drugs such as paclitaxel, the fluorescence of the cells changed from green to blue. We developed this method into a high-throughput assay in 96-well plates by measuring the emission ratio of yellow fluorescent protein (YFP) to cyan fluorescent protein (CFP) to monitor the activation of a key protease, caspase-3, during apoptosis.

5-Formylhonokiol exerts anti-angiogenesis activity via inactivating the ERK signaling pathway.

Our previous report has demonstrated that 5-formylhonokiol (FH), a derivative of honokiol (HK), exerts more potent anti-proliferative activities than honokiol in several tumor cell lines. In present study, we first explored the antiangiogenic activities of 5-formylhonokiol on proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) for the first time in vitro. Then we investigated the in vivo antiangiogenic effect of 5-formylhonokiol on zebrafish angiogenesis model.

Rational design of fluorescent bioimaging probes by controlling the aggregation behavior of squaraines: a special effect of ionic liquid pendants.

We herein present an effective strategy to create water-soluble fluorescent bioimaging dyes by introducing the imidazolium-based ionic liquid (IL) pendants into a fluorescent skeleton. A new type of water-soluble imidazolium-anchored squaraine dye was synthesized accordingly. The relationship between the aggregate of squaraines and their fluorescent cell imaging application was elucidated in detail.

Improved tumor-targeting drug delivery and therapeutic efficacy by cationic liposome modified with truncated bFGF peptide.

Fibroblast growth factor receptors (FGFRs), overexpressed on the surface of a variety of tumor cells and on tumor neovasculature in situ, are potential targets for tumor- and vascular-targeting therapy. This study aimed to develop a FGFR-mediated drug delivery system to target chemotherapeutic agents to FGFR-overexpressed tumor cells and tumor neovasculature endothelial cells in vitro and in vivo. Here we designed a truncated human basic fibroblast growth factor peptide (tbFGF), which was attached to the surface of cationic liposomal doxorubicin (LPs-DOX) and paclitaxel (LPs-PTX) via electrostatic force.