Search

Platelets buoy up cancer metastasis via arresting cancer cells, enhancing their adhesion, and facilitating their extravasation through the vasculature. When deprived of intracellular and granular contents, platelet decoys could prevent metastatic tumor formation. Inspired by these, we developed nanoplatesomes by fusing platelet membranes with lipid membranes (P-Lipo) to restrain metastatic tumor formation more efficiently. It was shown nanoplateletsomes bound with circulating tumor cells (CTC) efficiently, interfered with CTC arrest by vessel endothelial cells, CTC extravasation through endothelial layers, and epithelial-mesenchymal transition of tumor cells as nanodecoys. More importantly, in the mouse breast tumor metastasis model, nanoplateletsomes could decrease CTC survival in the blood and counteract metastatic tumor growth efficiently by inhibiting the inflammation and suppressing CTC escape. Therefore, nanoplatelesomes might usher in a new avenue to suppress lung metastasis. Nanoplateletsomes were inaugurated to restrain metastatic tumor formation efficiently through decoy and active targeting, serving as a platform to orchestrate the inhibition of circulating tumor cell survival and metastasis. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: To develop an apparatus for simultaneous monitoring of heart and respiratory rates using photoplethysmography (PPG) and Fast Fourier Transform algorithm (FFT), the PPG waveform was measured at the radial artery with an original based on diffuse reflectance mode photoplethysmographic device. An FFT algorithm was used to extract heart and respiratory information from the PPG waveform. The results good agree with conventional method. The correlation coefficient of heart rate and respiratory rate obtained using PPG waveform and conventional method is 0.988 and 0.976, respectively. The PPG waveform and FFT algorithm can contribute to quicker and more accurate measurement of human heart rate and respiration rate. A portable watch-like device can be made via this method and be utilized to monitor heart and respiratory rates in hospitals or daily life care. [Copyright &y& Elsevier]

Antiangiogenesis therapy has been served as a potent cancer treatment strategy for decades, yet disrupting neovasculature would provoke tumor cells into invasive growth and result in distal metastasis. The basic cause of cancer metastasis can be traced down to the presence of circulating tumor cells (CTCs) which detach from primary tumor site and act as ‘seeds’. Epithelial cell adhesion molecule (EpCAM) is a potential biomarker for selective capture of epithelium-derived CTCs. Here, we integrated tumor neovessles-targetable ligands K237 peptide with Ep23 aptamer against EpCAM into a single drug-loaded nanoplatform using paclitaxel (PTX) as the model drug, aiming at damaging the primary tumor and neutralizing CTCs simultaneously to achieve a synergistic anti-tumor therapeutic effect. Enhanced cellular uptake, cell apoptosis-induction and cell-viability inhibition efficiency of the peptide and aptamer dual-functionalized nanoparticles (dTNP) were observed in both human umbilical vein endothelial cells (HUVEC) and 4T1 cells in vitro . Using cone-and-plate viscometer to create venous flow velocity, dTNP was also found to be able to capture CTCs under shear stress. The CTC-targeting and neutralization effect of dTNP in bloodstream and 4T1-GFP cell-derived lung metastasis mice model was confirmed via in vivo flow cytometry (IVFC), intravital imaging and confocal microscopy analysis. As a result, the orthotropic breast tumor-bearing mice administrated with PTX-loaded dTNP exhibited the optimal therapeutic effect. Taken together, the findings here provided direct evidence that the tumor neovasculature and CTCs dual-targeting drug delivery system could provide a novel modality for the treatment of highly-invasive breast cancer. [ABSTRACT FROM AUTHOR]

NADH shuttles, including malate-aspartate shuttle (MAS) and glycerol-3-phosphate shuttle, can shuttle the reducing equivalents of cytosolic NADH into mitochondria. It is widely accepted that the major function of NADH shuttles is to increase mitochondrial energy production. Our study tested the hypothesis that the novel major function of NADH shuttles in cancer cells is to maintain glycolysis by decreasing cytosolic NADH/NAD(+) ratios. We found that AOAA, a widely used MAS inhibitor, led to decreased intracellular ATP levels, altered cell cycle and increased apoptosis and necrosis of C6 glioma cells, without affecting the survival of primary astrocyte cultures. AOAA also decreased the glycolytic rate and the levels of extracellular lactate and pyruvate, without affecting the mitochondrial membrane potential of C6 cells. Moreover, the toxic effects of AOAA were completely prevented by pyruvate treatment. Collectively, our study has suggested that AOAA may be used to selectively decrease glioma cell survival, and the major function of MAS in cancer cells may be profoundly different from its major function in normal cells: The major function of MAS in cancer cells is to maintain glycolysis, instead of increasing mitochondrial energy metabolism. [ABSTRACT FROM AUTHOR]

Highlights: [•] NAD+ treatment can decrease rotenone-induced early-stage and late-stage apoptosis of PC12 cells. [•] NAD+ treatment can decrease rotenone-induced necrosis of PC12 cells. [•] NAD+ treatment can restore the intracellular NAD+ levels of rotenone-treated PC12 cells. [•] NAD+ treatment can prevent rotenone-induced mitochondrial depolarization of PC12 cells. [Copyright &y& Elsevier]

Highlights: [•] The SIRT2 inhibitor AGK2 can induce both late-stage apoptosis and necrosis of microglial BV2 cells. [•] The SIRT2 inhibitor AGK2 can induce a decrease in the intracellular ATP levels of microglial BV2 cells. [•] Poly(ADP-ribose) polymerase activation mediates both the cell death and the ATP decline of AGK2-treated microglial BV2 cells. [ABSTRACT FROM AUTHOR]

Abstract: Confocal fluorescence imaging and fluorescence resonance energy transfer (FRET) technology have been widely used to study protein–protein interactions in living cells. However, it is very difficult to quantitatively analyze FRET efficiency due to the excitation spectral crosstalk and emission spectral crosstalk between donor and acceptor. In this study, we developed a novel method to quantitatively obtain the FRET efficiency by fitting the emission spectra (FES) of donor–acceptor pair, and this method is free from both excitation and emission spectral crosstalk. We used the FES method to quantitatively monitor the FRET efficiency of SCAT3, a caspase-3 indicator based on FRET, inside living cells stably expressing SCAT3 during STS-induced apoptosis. At 0, 6 and 12h after STS treatment, the FRET efficiency of SCAT3 obtained by FES are consistent with that by two-photon excitation (TPE) fluorescence lifetime imaging microscopy (FLIM) in living cells stably expressing SCAT3. In this study, the FES was also used to analyze the caspase-3 activation in living cells during anti-cancer drug such as taxol, Artesunate (ART) or Dihydroartemisinin (DHA) treatment. Our results showed that ART or DHA induced apoptosis by a caspase-3-dependent manner, while caspase-3 was not involved in taxol-induced cell death. [Copyright &y& Elsevier]

Cancer severely threatens human health currently, promoting the rapid development of cancer treatment strategies. In addition to cancer therapy, assessment of cancer prognosis, which can evaluate the success with treatment and chances of recovery as well as assist to make subsequent therapeutic schedule, is also remarkably indispensable and important. Conventional technologies can't provide rapid and highly-sensitive assessment of cancer prognosis at cytological level. Herein, an effective nitrogen doped carbon dots with intrinsic nucleolus-targeting capability and high fluorescence quantum yield are synthesized, characterized and employed for fluorescence imaging of nucleolus, which is closely related to the biological alteration of cancer cell. The cancer prognosis thus can be accurately (limit of detection: 50 nM) and rapidly (5 min) assessed at subcellular organelle level from nucleolar characteristics, which are visualized and analyzed by the captured fluorescence images. Outstanding assessment performance endows the proposed technology with great potential for future clinical research. [Display omitted] • Nitrogen doped carbon dots are synthesized for fluorescence imaging of nucleolus related to the biological alteration of cancer cell. • The cancer prognosis can be assessed at subcellular organelle level, which is not achievable using conventional technologies. • The proposed assessment method for cancer prognosis shows faster and more sensitive features as compared with AgNOR method. [ABSTRACT FROM AUTHOR]