Microencapsulation of Lefty-secreting engineered cells for pulmonary fibrosis therapy in mice.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that causes unremitting deposition of extracellular matrix proteins, thus resulting in distortion of the pulmonary architecture and impaired gas exchange. Associated with high morbidity and mortality, IPF is generally refractory to current pharmacological therapies. Lefty A, a potent inhibitor of transforming growth factor-ß signaling, has been shown to have promising antifibrotic ability in vitro for the treatment of renal fibrosis and other potential organ fibroses. Here, we determined whether Lefty A can attenuate bleomycin (BLM)-induced pulmonary fibrosis in vivo based on a novel therapeutic strategy where human embryonic kidney 293 (HEK293) cells are genetically engineered with the Lefty A-associated GFP gene. The engineered HEK293 cells were encapsulated in alginate microcapsules and then subcutaneously implanted in ICR mice that had 1 wk earlier been intratracheally administered BLM to induce pulmonary fibrosis. The severity of fibrosis in lung tissue was assessed using pathological morphology and collagen expression to examine the effect of Lefty A released from the microencapsulated cells. The engineered HEK293 cells with Lefty A significantly reduced the expression of connective tissue growth factor and collagen type I mRNA, lessened the morphological fibrotic effects induced by BLM, and increased the expression of matrix metalloproteinase-9. This illustrates that engineered HEK293 cells with Lefty A can attenuate pulmonary fibrosis in vivo, thus providing a novel method to treat human pulmonary fibrotic disease and other organ fibroses.

Saponins from the Sea Cucumber Promote the Osteoblast Differentiation in MC3T3-E1 Cells through the Activation of the BMP2/ Smads Pathway.

BACKGROUND: Several studies have shown that plant saponins promoted osteoblast differentiation and improved osteoporosis. In the current study, Sea Cucumber Saponin (SCS) with a purity of 80% was extracted from Filipino sea cucumber, with a similar structure to plant saponins. OBJECTIVE: This study aims to investigate the effects of SCS on bone formation in vitro and ex vivo. RESULTS: SCS significantly promoted osteogenic differentiation and mineralization of MC3T3-E1 cells, as well as new osteoid formation in neonatal mouse calvarias ex vivo. qRT-PCR results indicated that SCS markedly down-regulated the expression of C/EBPα* and PPARγ at the levels of transcription, which demonstrate that SCS inhibits the trans-differentiation of MC3T3-E1 cells to an adipocytic phenotype. Moreover, further studies revealed that SCS increased the expression levels of Runx2 and OSX. The mechanism revealed that SCS induced the expression of BMP2 and p-Smad1/5, which indicated that SCS facilitated osteogenesis via activating the BMP2/Smads signaling pathway. CONCLUSION: SCS promoted osteogenic differentiation of pre-osteoblasts by activating the BMP2/ Smads molecular pathway, providing a theoretical basis for the development of sea cucumber saponins for the treatment to bone loss diseases such as osteoporosis.

Evaluation of perfusion MRI value for tumor progression assessment after glioma radiotherapy: A systematic review and meta-analysis.

OBJECTIVES: This study aimed to evaluate the diagnostic performance of magnetic resonance perfusion-weighted imaging (PWI) as a noninvasive method to assess post-treatment radiation effect and tumor progression in patients with glioma. METHODS: A systematic literature search was performed in the PubMed, Cochrane Library, and Embase databases up to March 2020. The quality of the included studies was assessed by the quality assessment of diagnostic accuracy studies 2. Data were extracted to calculate sensitivity, specificity, and diagnostic odds ratio (DOR), 95% Confidence interval (CI) and analyze the heterogeneity of the studies (Spearman correlation coefficient, I2 test). We performed meta-regression and subgroup analyses to identify the impact of study heterogeneity. RESULTS: Twenty studies were included, with available data for analysis on 939 patients and 968 lesions. All included studies used dynamic susceptibility contrast (DSC) PWI, four also used dynamic contrast-enhanced PWI, and three also used arterial spin marker imaging PWI. When DSC was considered, the pooled sensitivity and specificity were 0.83 (95% CI, 0.79 to 0.86) and 0.83 (95% CI, 0.78 to 0.87), respectively; pooled DOR, 21.31 (95% CI, 13.07 to 34.73); area under the curve (AUC), 0.887; Q∗, 0.8176. In studies using dynamic contrast-enhanced, the pooled sensitivity and specificity were 0.73 (95% CI, 0.66 to 0.80) and 0.80 (95% CI, 0.69 to 0.88), respectively; pooled DOR, 10.83 (95% CI, 2.01 to 58.43); AUC, 0.9416; Q∗, 0.8795. In studies using arterial spin labeling, the pooled sensitivity and specificity were 0.79 (95% CI, 0.69 to 0.87) and 0.78 (95% CI, 0.67 to 0.87), respectively; pooled DOR, 15.63 (95% CI, 4.61 to 53.02); AUC, 0.8786; Q∗, 0.809. CONCLUSIONS: Perfusion magnetic resonance imaging displays moderate overall accuracy in identifying post-treatment radiation effect and tumor progression in patients with glioma. Based on the current evidence, DSC-PWI is a relatively reliable option for assessing tumor progression after glioma radiotherapy.

Deep Fano resonance with strong polarization dependence in gold nanoplate-nanosphere heterodimers.

Plasmonic Fano resonance arises from the destructive interference between a superradiant and a subradiant plasmon mode that overlap spectrally with each other. Because of its importance in revealing many physical phenomena and its applications in sensing, metamaterials, photoswitching and spectroscopy, a variety of metal nanostructures have been fabricated to generate Fano resonance. However, few metal nanostructures can support deep Fano resonance with strong polarization dependence. Herein, we report on the observation of deep Fano resonance with strong polarization dependence in Au nanoplate-nanosphere heterodimers. Experiments and simulations reveal that the presence of a nanosphere at one side edge or one vertex of the nanoplate causes distinct Fano resonance. With increasing nanosphere sizes, the shape of the scattering spectrum becomes more asymmetric, with the Fano dip getting deeper correspondingly. When the nanosphere diameter reaches 68 nm, the Fano dip almost reaches the spectral background. Moreover, the heterodimers with the nanosphere attached to one vertex of the nanoplate exhibit Fano resonance with strong polarization dependence. Such heterodimers are very attractive for constructing polarization-controlled plasmonic Fano switches.

miRNA-214 Inhibits Cellular Proliferation and Migration in Glioma Cells Targeting Caspase 1 Involved in Pyroptosis.

Pyroptosis is a type of proinflammatory programmed cell death mediated by caspase 1 activity and occurs in several types of eukaryotic tumor cells, including gliomas. MicroRNAs (miRNAs), small endogenous noncoding RNAs, have been demonstrated to be advantageous in glioma therapy. However, the question of whether miRNAs regulate pyroptosis in glioma remains unknown. The current study found that caspase 1 expression was substantially increased in both glioma tissues and glioma cell lines, U87 and T98G, while miR-214 expression was significantly downregulated. Luciferase reporter assay recognized caspase 1 as a target gene of miR-214. These findings demonstrate that miR-214 could inhibit cell proliferation and migration through the regulation of pyroptosis intermediated by caspase 1 in glioma U87 and T98G cells and may suggest a novel therapeutic for the intervention of glioma.

Role of shape in substrate-induced plasmonic shift and mode uncovering on gold nanocrystals.

A number of plasmonic devices and applications, such as chemical and biological sensors, plasmon-enhanced solar cells, optical nanoantennas, metamaterials and metasurfaces, require the deposition of plasmonic metal nanocrystals on various substrates. Because the localized plasmon resonance modes, energies and strengths are strongly dependent on the dielectric function of the surrounding environment, the substrate is expected to largely affect the plasmonic properties of supported metal nanocrystals. Therefore, understanding the effects of the substrate on the plasmonic properties of metal nanocrystals and the roles of the involved factors will be crucial for designing various plasmonic devices that are made of metal nanocrystals deposited on different substrates. Herein we report on our study and results of the effects of substrates with distinct dielectric functions on the plasmonic properties of three types of Au nanocrystals. A combination of experiments and numerical simulations shows that the presence of a substrate causes plasmonic shifts as well as the appearance of new plasmon modes. The plasmonic shifts and the emergence of new plasmon modes are found to be dependent on the particle shape of Au nanocrystals and in turn on the fractional particle surface area that is in contact with the supporting substrate. For Au nanospheres and nanorods, plasmonic shifts, less than 100 nm, are observed on the scattering spectra by changing the supporting substrate from indium tin oxide to silicon. In comparison, a giant spectral shift of more than 300 nm is obtained for Au nanoplates. Moreover, silicon substrates induce the emergence of an out-of-plane quadrupolar mode of Au nanoplates, which interacts with an out-of-plane octupolar mode to give rise to a distinct Fano resonance. The Fano resonance is found to become stronger as the thickness of Au nanoplates is decreased. These results are of great importance for understanding the plasmonic properties of noble metal nanocrystals supported on various substrates, and for designing novel plasmonic nanostructures with desired optical properties and functions.