Functionalized halloysite nanotube-based carrier for intracellular delivery of antisense oligonucleotides

Halloysites are cheap, abundantly available, and natural with high mechanical strength and biocompatibility. In this paper, a novel halloysite nanotube [HNT]-based gene delivery system was explored for loading and intracellular delivery of antisense oligodeoxynucleotides [ASODNs], in which functionalized HNTs [f-HNTs] were used as carriers and ASODNs as a therapeutic gene for targeting survivin. HNTs were firstly surface-modified with γ-aminopropyltriethoxysilane in order to facilitate further biofunctionalization. The f-HNTs and the assembled f-HNT-ASODN complexes were characterized by transmission electron microscopy [TEM], dynamic light scattering, UV-visible spectroscopy, and fluorescence spectrophotometry. The intracellular uptake and delivery efficiency of the complexes were effectively investigated by TEM, confocal microscopy, and flow cytometry. In vitro cytotoxicity studies of the complexes using MTT assay exhibited a significant enhancement in the cytotoxic capability. The results exhibited that f-HNT complexes could efficiently improve intracellular delivery and enhance antitumor activity of ASODNs by the nanotube carrier and could be used as novel promising vectors for gene therapy applications, which is attributed to their advantages over structures and features including a unique tubular structure, large aspect ratio, natural availability, rich functionality, good biocompatibility, and high mechanical strength

Cancer type-specific modulation of mitochondrial haplogroups in breast, colorectal and thyroid cancer

<p>Abstract</p> <p>Background</p> <p>Mitochondrial DNA (mtDNA) haplogroups and single nucleotide polymorphisms (mtSNP) have been shown to play a role in various human conditions including aging and some neurodegenerative diseases, metabolic diseases and cancer.</p> <p>Methods</p> <p>To investigate whether mtDNA haplogroups contribute to the occurrence of cancer in a specific Chinese population, we have carried out a comprehensive case-control study of mtDNA from large cohorts of patients with three common cancer types, namely, colorectal cancer (n = 108), thyroid cancer (n = 100) and breast cancer (n = 104), in Wenzhou, a southern Chinese city in the Zhejiang Province.</p> <p>Results</p> <p>We found that patients with mtDNA haplogroup M exhibited an increased risk of breast cancer occurrence [OR = 1.77; 95% CI (1.03-3.07); P = 0.040], and that this risk was even more pronounced in a sub-haplogroup of M, D5 [OR = 3.11; 95%CI (1.07-9.06); p = 0.030]. In spite of this, in patients with breast cancer, haplogroup M was decreased in the metastatic group. On the other hand, our results also showed that haplogroup D4a was associated with an increased risk of thyroid cancer [OR = 3.00; 95%CI (1.09-8.29); p = 0.028]. However, no significant correlation has been detected between any mtDNA haplogroups and colorectal cancer occurrence.</p> <p>Conclusion</p> <p>Our investigation indicates that mitochondrial haplogroups could have a tissue-specific, population-specific and stage-specific role in modulating cancer development.</p

MicroRNA-483 amelioration of experimental pulmonary hypertension.

Endothelial dysfunction is critically involved in the pathogenesis of pulmonary arterial hypertension (PAH) and that exogenously administered microRNA may be of therapeutic benefit. Lower levels of miR-483 were found in serum from patients with idiopathic pulmonary arterial hypertension (IPAH), particularly those with more severe disease. RNA-seq and bioinformatics analyses showed that miR-483 targets several PAH-related genes, including transforming growth factor-β (TGF-β), TGF-β receptor 2 (TGFBR2), β-catenin, connective tissue growth factor (CTGF), interleukin-1β (IL-1β), and endothelin-1 (ET-1). Overexpression of miR-483 in ECs inhibited inflammatory and fibrogenic responses, revealed by the decreased expression of TGF-β, TGFBR2, β-catenin, CTGF, IL-1β, and ET-1. In contrast, inhibition of miR-483 increased these genes in ECs. Rats with EC-specific miR-483 overexpression exhibited ameliorated pulmonary hypertension (PH) and reduced right ventricular hypertrophy on challenge with monocrotaline (MCT) or Sugen + hypoxia. A reversal effect was observed in rats that received MCT with inhaled lentivirus overexpressing miR-483. These results indicate that PAH is associated with a reduced level of miR-483 and that miR-483 might reduce experimental PH by inhibition of multiple adverse responses

The adaptors Grb10 and Grb14 are calmodulin-binding proteins

We identified the Grb7 family members, Grb10 and Grb14, as Ca2+-dependent CaM-binding proteins using Ca2+-dependent CaM-affinity chromatography as we previously did with Grb7. The potential CaM-binding sites were identified and experimentally tested using fluorescent-labeled peptides corresponding to these sites. The apparent affinity constant of these peptides for CaM, and the minimum number of calcium ions bound to CaM that are required for effective binding to these peptides were also determined. We prepared deletion mutants of the three adaptor proteins lacking the identified sites and determined that they lost or strongly diminished their CaM-binding capacity following the sequence Grb7 > > Grb14 > Grb10. More than one CaM-binding site and/or accessory CaM-binding sites appear to exist in Grb10 and Grb14, as compared to a single one present in Grb7.Secretaría de Estado de Investigación, Desarrollo e Innovación SAF2011-23494, SAF2014-52048-

Strain-based tunable optical microresonator with an in-fiber rectangular air bubble

We demonstrate a strain-based fully tunable, near-lossless, whispering gallery mode (WGM) resonator made of an in-fiber rectangular air bubble, which is fabricated by splicing two segments of standard single-mode fibers. Such a resonator, with a 39 μm order radius and 1 μm order wall thickness, contributes to a high quality factor exceeding 106. The tuning in resonant wavelength is achieved by applying tensile strain to the resonator, and the voltage-tuning rate of the WGM resonance peaks is about 31.96 pm/V (strain-tuning rate ∼14.12 pm∕με), and the corresponding tuning accuracy is better than 0.03 pm. Since the tensile strain applied on the resonator can reach 1000 με, the achievable total tunable bandwidth of ∼14.12 nm is more than two times that of its azimuthal free spectral range

Effect of evaporator/condenser elevations on a loop heat pipe with non-condensable gas

The coupling effect of evaporator/condenser elevations and non-condensable gas (NCG) on the performance of a loop heat pipe (LHP) operating in gravitational field was investigated experimentally. Ammonia and nitrogen were selected as the working fluid of LHP and the simulated gas of NCG, respectively. The experiments were conducted at three kinds of evaporator/condenser elevations, namely zero elevation, adverse elevation and positive elevation. Experimental results show that NCG will cause an increase in operating temperature, but the trends varies at different evaporator/condenser elevation elevations. The temperature rises caused by NCG at the zero and adverse elevations are negatively correlated with heat load, and the maximum temperature increments are both at the minimum heat load of 15 W, but the influence of NCG is less at adverse elevation. On the other hand, at favorable elevation, the temperature rise exhibits different characteristics in different LHP operation modes, i.e., positively correlated with heat load in gravity driven mode and negatively in capillarity-gravity co-driven mode, and the transition heat load is 60 W. For an LHP that has already contained a certain amount of NCG, functioning at favorable elevation could eliminate the adverse effects of NCG on operating temperature and heat transfer performance to some extent. Furthermore, it is found that the presence of NCG and adverse elevation appears to inhibit the backflow during startup and improve startup stability. These results might have reference significance for the design and installation of the LHP for terrestrial applications