Cardiovascular-specific PSEN1 deletion leads to abnormalities in calcium homeostasis.

Mutations of PSEN1 have been reported in dilated cardiomyopathy pedigrees. Understanding the effects and mechanisms of PSEN1 in cardiomyocytes might have important implications for treatment of heart diseases. Here, we showed that PSEN1 was downregulated in ischemia-induced failing hearts.

CAR exosomes derived from effector CAR-T cells have potent antitumour effects and low toxicity.

Genetically engineered T cells expressing a chimeric antigen receptor (CAR) are rapidly emerging a promising new treatment for haematological and non-haematological malignancies. CAR-T therapy can induce rapid and durable clinical responses but is associated with unique acute toxicities. Moreover, CAR-T cells are vulnerable to immunosuppressive mechanisms.

Targeting RyR2 with a phosphorylation site-specific nanobody reverses dysfunction of failing cardiomyocytes in rats.

Chronic PKA phosphorylation of ryanodine receptor 2 (RyR2) has been shown to increase diastolic sarcoplasmic reticulum (SR) Ca leakage and lead to cardiac dysfunction. We hypothesize that intracellular gene delivery of an RyR2-targeting phosphorylation site-specific nanobody could preserve the contractility of the failing myocardium. In the present study, we acquired RyR2-specific nanobodies from a phage display library that were variable domains of heavy chain-only antibodies.

EGFR/Notch Antagonists Enhance the Response to Inhibitors of the PI3K-Akt Pathway by Decreasing Tumor-Initiating Cell Frequency.

Purpose: Both EGFR and PI3K-Akt signaling pathways have been used as therapeutically actionable targets, but resistance is frequently reported. In this report, we show that enrichment of the cancer stem cell (CSC) subsets and dysregulation of Notch signaling underlie the challenges to therapy and describe the development of bispecific antibodies targeting both HER and Notch signaling.

Experimental Design: We utilized cell-based models to study Notch signaling in drug-induced CSC expansion.

Tumor Ablation Enhancement by Combining Radiofrequency Ablation and Irreversible Electroporation: An In Vitro 3D Tumor Study.

We hypothesized and demonstrated for the first time that significant tumor ablation enhancement can be achieved by combining radiofrequency ablation (RFA) and irreversible electroporation (IRE) using a 3D cervical cancer cell model. Three RFA (43, 50, and 60 °C for 2 min) and IRE protocols (350, 700, and 1050 V/cm) were used to study the combining effect in the 3D tumor cell model. The in vitro experiment showed that both RFA enhanced IRE and IRE enhanced RFA can lead to a significant increase in the size of the ablation zone compared to IRE and RFA alone.

Development of a statistical model for cervical cancer cell death with irreversible electroporation in vitro.

Purpose: The aim of this study was to develop a statistical model for cell death by irreversible electroporation (IRE) and to show that the statistic model is more accurate than the electric field threshold model in the literature using cervical cancer cells in vitro.

Methods: HeLa cell line was cultured and treated with different IRE protocols in order to obtain data for modeling the statistical relationship between the cell death and pulse-setting parameters. In total, 340 in vitro experiments were performed with a commercial IRE pulse system, including a pulse generator and an electric cuvette.

Cardiac adenovirus-associated viral Presenilin 1 gene delivery protects the left ventricular function of the heart via regulating RyR2 function in post-ischaemic heart failure.

Post-ischaemic heart failure is a major cause of death worldwide. Reperfusion of infarcted heart tissue after myocardial infarction has been an important medical intervention to improve outcomes. However, disturbances in Ca and redox homeostasis at the cellular level caused by ischaemia/reperfusion remain major clinical challenges.

Conditionally targeted deletion of PSEN1 leads to diastolic heart dysfunction.

Recently, PSEN1 has been reported to have mutations in dilated cardiomyopathy pedigrees. However, the function and mechanism of PSEN1 in cardiomyopathy remains unresolved. Here, we established four types of genetically modified mice to determine the function of PSEN1 in cardiac development and pathology.

Antagonism of EGFR and Notch limits resistance to EGFR inhibitors and radiation by decreasing tumor-initiating cell frequency.

Epidermal growth factor receptor (EGFR) blockade and radiation are efficacious in the treatment of cancer, but resistance is commonly reported. Studies have suggested that dysregulation of Notch signaling and enrichment of the cancer stem cell population underlie these treatment challenges. Our data show that dual targeting of EGFR and Notch2/3 receptors with antibody CT16 not only inhibited signaling mediated by these receptors but also showed a strong anti-stem cell effect both in vitro and in vivo.

TRIM14 regulates cell proliferation and invasion in osteosarcoma via promotion of the AKT signaling pathway.

Recent studies have shown that some members of the tripartite motif-containing protein (TRIM) family serve as important regulators of tumorigenesis. However, the biological role of TRIM14 in osteosarcoma remains to be established. In this study, we showed that TRIM14 is upregulated in human osteosarcoma specimens and cell lines, and correlated with osteosarcoma progression and shorter patient survival times.

CoNi@SiO2 @TiO2 and CoNi@Air@TiO2 Microspheres with Strong Wideband Microwave Absorption.

The synthesis of CoNi@SiO2 @TiO2 core-shell and CoNi@Air@TiO2 yolk-shell microspheres is reported for the first time. Owing to the magnetic-dielectric synergistic effect, the obtained CoNi@SiO2 @TiO2 microspheres exhibit outstanding microwave absorption performance with a maximum reflection loss of -58.2 dB and wide bandwidth of 8.

Distribution of graphene oxide and TiO2-graphene oxide composite in A549 cells.

Graphene and its derivatives are increasingly applied in nanoelectronics, biosensing, drug delivery, and biomedical applications. However, the information about its cytotoxicity remains limited. Herein, the distribution and cytotoxicity of graphene oxide (GO) and TiO2-graphene oxide composite (TiO2-GO composite) were evaluated in A549 cells.

Effects of fullerene C₆₀ nanoparticles on A549 cells.

Fullerene C60 nanoparticles (C60 NPs) have been widely applied in many fields due to their excellent physical and chemical properties. As production and applications of C60 NPs expand, public concern about the potential risk to human health has also risen. The toxicity of C60 NPs was evaluated by the CCK-8 assay using the cultured human epithelial cell line A549.

Mesenchymal stem cells with modification of junctional adhesion molecule a induce hair formation.

The junctional adhesion molecule A (JAM-A) has been shown to serve a crucial role in the proliferation, differentiation, and tube-like formation of epithelial cells during angiogenesis. The role of JAM-A in hair follicle (HF) regeneration has not yet been reported. In this study, we used human JAM-A-modified human mesenchymal stem cells (MSCs) to repair HF abnormalities in BALB/c nu/nu mice.

Cytotoxicity of silica nanoparticles on HaCaT cells.

Despite the widespread use of silica nanoparticles (SiO2 NPs) in biological and medical fields, their adverse effects have not been clearly elucidated. In this study, spherical SiO2 NPs with a 50 nm diameter were used to study their interaction with HaCaT cells. SiO2 NPs were found to be readily internalized into HaCaT cells and localized in the cytoplasm, lysosomes and autophagosomes.

Mitochondrial injury induced by nanosized titanium dioxide in A549 cells and rats.

The nanosized titanium dioxide (nano-TiO2) is an important nanoscale compound applied in many different fields because of its superior performance. Here, an anatase nano-TiO2 showed cytotoxicity in a dosage-dependent manner, which was in accordance with changes of A549 cell ultrastructure, A549 cell viability and intracellular ATP level. The lungs of rats treated with single intratracheal instillation of nano-TiO2 were injured, which was demonstrated by changes of alveolar epithelial cell ultrastructure, lung tissue pathology and lung tissue MDA level.

Dexamethasone induces rapid promotion of norepinephrine‑mediated vascular smooth muscle cell contraction.

The aim of the present study was to identify the rapid effect of dexamethasone (Dex) on norepinephrine (NE)‑mediated contraction of vascular smooth muscle cells (VSMCs) and to establish the underlying mechanism(s). Rat VSMCs were preincubated with lipopolysaccharide to simulate acute septic shock. Myosin light chain (MLC20) phosphorylation of VSMCs was detected by western blot analysis to observe the effects of Dex on NE‑mediated contraction.

Maximizing the relaxivity of Gd-complex by synergistic effect of HSA and carboxylfullerene.

Macromolecular magnetic resonance imaging (MRI) contrast agent Gd-DTPA-HSA (DTPA, diethylene triamine pentacetate acid; HSA, human serum albumin) as a model has been successfully conjugated with trimalonic acid modified C60 for contrast enhancement at clinically used magnetic field strength. The Gd-DTPA-HSA-C60 conjugate exhibit maximal relaxivity (r1 = 86 mM(-1) s(-1) at 0.5 T, 300 K) reported so far, which is much superior to that of the control Gd-DTPA-HSA (r1 = 38 mM(-1 )s(-1)) under the same condition and comparable to the theoretical maximum (r1 = 80-120 mM(-1) s(-1), at 20 MHz and 298 K), indicating the synergistic effect of HSA and carboxylfullerene on the increased contrast enhancement.

Multifunctional imaging probe based on gadofulleride nanoplatform.

A FAR over-expressed tumor targeting multifunctional imaging probe has been fabricated based on gadofulleride nanoplatform. The combination of highly efficient MRI contrast enhancement and sensitive fluorescence imaging along with the preferential uptake toward FAR tumor cells suggest that the obtained multifunctional imaging probe possesses complementary capabilities for anatomical resolution and detection sensitivity.

Structural effect and mechanism of C70-carboxyfullerenes as efficient sensitizers against cancer cells.

Carboxyfullerenes with different adduct numbers and cage sizes are tested as photosensitizers for photodynamic therapy (PDT). The photodynamic efficiency of these carboxyfullerenes depends mainly on the cage size, C(60) versus C(70) , and to a lesser extent on the adduct numbers. In particular, malonic acid modified C(70) fullerenes are more efficient than their C(60) counterparts as photosensitizers, and the mechanism of cell death induced by C(70) -carboxyfullerene under light irradiation is investigated in detail.

Noninjection facile synthesis of Gram-scale highly luminescent CdSe multipod nanocrystals.

Nearly all reported approaches for synthesis of high quality CdSe nanocrystals (NCs) involved two steps of preparation of Cd or Se stock solution in advance and then mixing the two reactants via hot-injection in high temperature. In this manuscript, Gram-scale CdSe multipod NCs were facilely synthesized in a noninjection route with the use of CdO and Se powder directly as reactants in paraffin reaction medium containing small amount of oleic acid and trioctylphosphine. The influence of various experimental variables, including reaction temperature, nature and amount of surfactants, Cd-to-Se ratio, and the nature of reactants, on the morphology of the obtained CdSe NCs have been systematically investigated.

Protective effect of oxymatrine on chronic rat heart failure.

Oxymatrine is one of the alkaloids extracted from the Chinese herb Sophora japonica (Sophora flavescens Ait.) with anti-inflammatory, immune reaction inhibiting, antiviral, and hepatocyte and antihepatic fibrosis protective activities. However, the effect of oxymatrine on heart failure is not yet known.