Search

Breast cancer treatment has been a global puzzle, and apoptosis strategies based on mitochondrial Ca2+ overload have attracted extensive attention. However, various limitations of current Ca2+ nanogenerators make it difficult to maintain effective Ca2+ overload concentrations. Here, we constructed a multimodal Ca2+ nano-modulator that, for the first time, combined photothermal therapy (PTT) and mitochondrial Ca2+ overload strategies to inhibit tumor development. By crosslinking sodium alginate (SA) on the surface of calcium carbonate (CaCO3) nanoparticles encapsulating with Cur and ICG, we prepared a synergistic Ca2+ nano-regulator SA/Cur@CaCO3-ICG (SCCI). In vitro studies have shown that SCCI further enhanced photostability while preserving the optical properties of ICG. After uptake by tumor cells, SCCI can reduce mitochondrial membrane potential and down-regulate ATP production by producing large amounts of Ca2+ at low pH. Near-infrared light radiation (NIR) laser irradiation made the tumor cells heat up sharply, which not only accelerated the decomposition of CaCO3, but also produced large amounts of reactive oxygen species (ROS) followed by cell apoptosis. In vivo studies have revealed that the Ca2+ nano-regulators had excellent targeting, biocompatibility, and anti-tumor effects, which can significantly inhibit the proliferation of tumor cells and play a direct killing effect. These findings indicated that therapeutic strategies based on ionic interference and PTT had great therapeutic potential, providing new insights into antitumor therapy. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine whether synchrotron radiation (SR)-based X-ray in-line phase-contrast imaging (IL-PCI) can be used to investigate the morphological characteristics of tumor neovascularization in a liver xenograft animal model.Methods: A human hepatocellular carcinoma HCCLM3 xenograft model was established in nude mice. Xenografts were sampled each week for 4 weeks and fixed to analyze tissue characteristics and neovascularization using SR-based X-ray in-line phase contrast computed tomography (IL-XPCT) without any contrast agent.Results: The effect of the energy level and object-to-detector distance on phase-contrast difference was in good agreement with the theory of IL-PCI. Boundaries between the tumor and adjacent normal tissues at week 1 were clearly observed in two-dimensional phase contrast projection imaging. A quantitative contrast difference was observed from weeks 1 to 4. Moreover, 3D image reconstruction of hepatocellular carcinoma (HCC) samples showed blood vessels inside the tumor were abnormal. The smallest blood vessels measured approximately 20 μm in diameter. The tumor vascular density initially increased and then decreased gradually over time. The maximum tumor vascular density was 4.29% at week 2.Conclusion: IL-XPCT successfully acquired images of neovascularization in HCC xenografts in nude mice. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine whether synchrotron radiation (SR)-based X-ray in-line phase-contrast imaging (IL-PCI) can be used to investigate the morphological characteristics of tumor neovascularization in a liver xenograft animal model., Methods: A human hepatocellular carcinoma HCCLM3 xenograft model was established in nude mice. Xenografts were sampled each week for 4 weeks and fixed to analyze tissue characteristics and neovascularization using SR-based X-ray in-line phase contrast computed tomography (IL-XPCT) without any contrast agent., Results: The effect of the energy level and object-to-detector distance on phase-contrast difference was in good agreement with the theory of IL-PCI. Boundaries between the tumor and adjacent normal tissues at week 1 were clearly observed in two-dimensional phase contrast projection imaging. A quantitative contrast difference was observed from weeks 1 to 4. Moreover, 3D image reconstruction of hepatocellular carcinoma (HCC) samples showed blood vessels inside the tumor were abnormal. The smallest blood vessels measured approximately 20 μm in diameter. The tumor vascular density initially increased and then decreased gradually over time. The maximum tumor vascular density was 4.29% at week 2., Conclusion: IL-XPCT successfully acquired images of neovascularization in HCC xenografts in nude mice.

Background: Concerted hormone secretion is essential for glucose homeostasis and growth. The oocyte testis gene 1 (Otg1) has limited information in mammals before. Human OTG1 has been identified as an antigen associated with cutaneous T cell lymphoma, while worm Otg1 is recently reported to be a vesicle trafficking regulator in neurons. To understand the physiological role of Otg1 and its potential relation to hormone secretion, we characterized a mutation caused by the piggyBac transposon (PB) insertion in mice., Results: Oocyte testis gene 1 encodes a Golgi localized protein that is expressed with a broad tissue distribution in mice. The PB insertion effectively blocks Otg1 expression, which results in postnatal lethality, growth retardation, hypoglycemia and improved insulin sensitivity in mice. Otg1 mutants exhibit decreased levels of insulin, leptin and growth hormone in the circulation and reduced hepatic IGF-1 expression. Decreased expression of Otg1 in pituitary GH3 cells causes reduced grow hormone expression and secretion, as well as the traffic of the VSVG protein marker., Conclusions: Our data support the hypothesis that Otg1 impacts hormone secretion by regulating vesicle trafficking. These results revealed a previously unknown and important role of Otg1 in hormone secretion and glucose homeostasis in mammals.

Background: Construction of electrochemical impedance sensors by the self-assembly technique has become a promising strategy for the 'label-free' detection of protein-ligand interactions. However, previous impedance sensors are devoid of an inherent electrochemical signal, which limits the standardization of the sensors for protein recognition in a reproducible manner., Results: We designed and synthesized an anthraquinonyl glycoside (AG) where the anthraquinone (AQ) moiety can bind to the surface of a graphene-based working electrode while the glycoside serving as a ligand for lectin. By measuring the inherent voltammetric signal of AQ, the glycosides decorated on the working electrode could be simply quantified to obtain electrodes with a unified signal window. Subsequently, impedance analysis showed that the 'standardized' electrodes gave a reproducible electrochemical response to a selective lectin with no signal variation in the presence of unselective proteins., Conclusion: Anthraquinone-modified ligands could be used to facilitate the standardization of electrochemical impedance sensors for the reproducible, selective analysis of ligand-protein interactions.