Animal heat activated cancer therapy by a traditional catalyst TiO2-Pd/graphene composites.

Cancer therapy is one of the most important challenges in clinical medicine. So far different methods have been developed for cancer therapy, such as radiation therapy, surgery, chemotherapy and photodynamic therapy. Here we propose a new concept for cancer therapy, i.e., killing the cancer cells simply via reactive oxygen species (ROS) generated by TiO2-Pd/graphene composites. Activated by animal heat of 37 °C, the electrons in the valence band can be excited to the conduction band of TiO2 via the energy levels of Pd species and graphene, generating ROS without light irradiation or electric excitation. The tumors in BALB/c mice are successfully regressed at animal heat without any other external conditions, such as radiation, UV, visible and IR irradiation. Our results suggest that the design of animal heat activated cancer therapy is a feasible concept for practical applications of cancer treatments.

Spatiotemporal Characteristics of Intercellular Calcium Wave Communication in Micropatterned Assemblies of Single Cells.

Micropatterned substrates offer a unique possibility to define and control spatial organization of biological cells at the microscale, which greatly facilitates investigations of the cell-to-cell communication in vitro. Here, we developed a simple micropatterning strategy to resolve various spatiotemporal characteristics of intercellular calcium wave (ICW) communication among isolated BV-2 microglial cells. By using a single-ring assembly, we found that the direction of the initial transmitter secretion was strongly correlated with the site of the cell at which the mechanical stimulus triggering the ICWs was imposed. By using multiring assemblies, we observed that the response ratio of the same outmost cells 160 µm away from the center increased from 0% in the single-ring assembly to 9.6% in the four-ring assembly. This revealed that cells located in the interring acted as regenerative amplifiers for the ICWs generated by the central cell. By using a special oval-type micropattern, we found that calcium mobilization in lamellipodia of a fusiform BV-2 microglia cell occurred 2.9 times faster than that in the middle part of the cell, demonstrating a higher region-specific sensitivity of lamellipodia to the transmitter. Taken together, our micropatterning strategy opened up new experimental prospects to study ICWs and revealed novel spatiotemporal characteristics of ICW communication including stimulation site-dependent secretion, regenerative propagation, and region-specific cell sensitivity.

Nucleotide transmitters ATP and ADP mediate intercellular calcium wave communication via P2Y12/13 receptors among BV-2 microglia.

Nerve injury is accompanied by a liberation of diverse nucleotides, some of which act as 'find/eat-me' signals in mediating neuron-glial interplay. Intercellular Ca2+ wave (ICW) communication is the main approach by which glial cells interact and coordinate with each other to execute immune defense. However, the detailed mechanisms on how these nucleotides participate in ICW communication remain largely unclear. In the present work, we employed a mechanical stimulus to an individual BV-2 microglia to simulate localized injury. Remarkable ICW propagation was observed no matter whether calcium was in the environment or not. Apyrase (ATP/ADP-hydrolyzing enzyme), suramin (broad-spectrum P2 receptor antagonist), 2-APB (IP3 receptor blocker) and thapsigargin (endoplasmic reticulum calcium pump inhibitor) potently inhibited these ICWs, respectively, indicating the dependence of nucleotide signals and P2Y receptors. Then, we detected the involvement of five naturally occurring nucleotides (ATP, ADP, UTP, UDP and UDP-glucose) by desensitizing receptors. Results showed that desensitization with ATP and ADP could block ICW propagation in a dose-dependent manner, whereas other nucleotides had little effect. Meanwhile, the expression of P2Y receptors in BV-2 microglia was identified and their contributions were analyzed, from which we suggested P2Y12/13 receptors activation mostly contributed to ICWs. Besides, we estimated that extracellular ATP and ADP concentration sensed by BV-2 microglia was about 0.3 µM during ICWs by analyzing calcium dynamic characteristics. Taken together, these results demonstrated that the nucleotides ATP and ADP were predominant signal transmitters in mechanical stimulation-induced ICW communication through acting on P2Y12/13 receptors in BV-2 microglia.

Protection of the biconcave profile of human erythrocytes against osmotic damage by ultraviolet-A irradiation through membrane-cytoskeleton enhancement.

To perform various physiological functions, erythrocytes possess a unique biconcave shape provided by a special architecture of the membrane-skeleton system. In the present work, we use a simple irradiation method to treat human erythrocytes with 365 nm ultraviolet-A (UVA) light at the single-cell level in vitro. Depending on the irradiation dose, UVA show protection of the biconcave profile against the detrimental action of distilled water. This protective effect can also be confirmed for saponin that damages the membrane-skeleton by vesiculation and pore formation. Interestingly, at two irradiation doses of UVA pretreatment, erythrocytes still seem to exhibit cell viability as tested by trypan blue assay even if distilled water or saponin is added. The oxidants hydrogen peroxide and cumene hydroperoxide partly simulate the protective effects. Taken together, these results demonstrate that 365 nm UVA irradiation can protect the biconcave profile of human erythrocytes through membrane-skeleton enhancement associated with a production of oxidants.

Cell-cell communication induces random spikes of spontaneous calcium oscillations in multi-BV-2 microglial cells.

As the first and main form of active immune defense in the central nervous system, microglial cells usually exhibit complicated intracellular calcium (Ca²âº) activity that can regulate the downstream components of signaling cascades. In the present work, spontaneous oscillations of the cytosolic calcium concentration ([Ca²âº]c) in multi-BV-2 microglial cells were observed by video microscopy. These cells exhibited random spikes of Ca²âº oscillations. Cross-correlation analysis of the temporal dependence of the oscillations indicated the existence of cell-cell communication mediated by extracellular messengers. Numerical simulations based on a simple mathematical model suggested that these communications could induce random spikes of spontaneous Ca oscillations in the multi-cell system. Short-time imaging analysis of random spikes in different regions of a single cell showed that spontaneous Ca²âº oscillations resulted from Ca²âº wave generated by other cells as well as from calcium elevation inside the cell. Taken together, our data demonstrate that cell-cell communication existed between the BV-2 microglial cells in vitro and further resulted in the random spikes of spontaneous Ca²âº oscillations.