The Fight against Cancer by Microgravity: The Multicellular Spheroid as a Metastasis Model

Cancer is a disease exhibiting uncontrollable cell growth and spreading to other parts of the organism. It is a heavy, worldwide burden for mankind with high morbidity and mortality. Therefore, groundbreaking research and innovations are necessary. Research in space under microgravity (µg) conditions is a novel approach with the potential to fight cancer and develop future cancer therapies. Space travel is accompanied by adverse effects on our health, and there is a need to counteract these health problems. On the cellular level, studies have shown that real (r-) and simulated (s-) µg impact survival, apoptosis, proliferation, migration, and adhesion as well as the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors in cancer cells. Moreover, the µg-environment induces in vitro 3D tumor models (multicellular spheroids and organoids) with a high potential for preclinical drug targeting, cancer drug development, and studying the processes of cancer progression and metastasis on a molecular level. This review focuses on the effects of r- and s-µg on different types of cells deriving from thyroid, breast, lung, skin, and prostate cancer, as well as tumors of the gastrointestinal tract. In addition, we summarize the current knowledge of the impact of µg on cancerous stem cells. The information demonstrates that µg has become an important new technology for increasing current knowledge of cancer biology.     

Prostaglandins suppress an outward potassium current in embryonic rat sensory neurons

One of the challenges in understanding ciliary and flagellar motility is determining the mechanisms that locally regulate dynein-driven microtubule sliding. Our recent studies demonstrated that microtubule sliding, in Chlamydomonas flagella, is regulated by phosphorylation. However, the regulatory proteins remain unknown. Here we identify the 138-kD intermediate chain of inner arm dynein I1 as the critical phosphoprotein required for regulation of motility. This conclusion is founded on the results of three different experimental approaches. First, genetic analysis and functional assays revealed that regulation of microtubule sliding, by phosphorylation, requires inner arm dynein I1. Second, in vitro phosphorylation indicated the 138-kD intermediate chain of I1 is the only phosphorylated subunit. Third, in vitro reconstitution demonstrated that phosphorylation and dephosphorylation of the 138-kD intermediate chain inhibits and restores wild-type microtubule sliding, respectively. We conclude that change in phosphorylation of the 138-kD intermediate chain of I1 regulates dynein-driven microtubule sliding. Moreover, based on these and other data, we predict that regulation of I1 activity is involved in modulation of flagellar waveform.     

Effect of natural oils on the thermal stability and degradation kinetics of recycled polypropylene wood flour composites

Recycled polypropylene was reinforced with wood fibers that were non‐treated and treated with different natural oils (hexanoic, octanoic, decanoic and dodecanoic acids). The thermal properties, morphology, kinetics and thermodynamic parameters were investigated. The use of natural oils as coupling agents clearly improved the interfacial adhesion with the matrix and increased the thermal stability of the composites. Octanoic acid improved the thermal stability of the composite the most compared with the other evaluated natural oils. The improvement caused by this natural oil is similar to that promoted by the addition of PPgMA. The thermal stability of the composite was affected by the boiling temperature and the chain length of the acid used. POLYM. COMPOS., 35:1935–1942, 2014. © 2014 Society of Plastics Engineers     

The combined influence of Mg and Ca on microstructural evolution of alumina

The solubility limits of Ca and Mg co-doped in alumina at 1600°C were determined by equilibrating alumina saturated with Ca and Mg. This resulted in the formation of MgAl₂O₄ (Mg spinel), CaO·6Al₂O₃ (CA6), Ca₂Mg₂Al₂₈O₄₆ (CAM-II), and alumina grains saturated with Mg and Ca. Under these conditions, the amount of Ca and Mg in the alumina grains represents the solubility limits. The solubility limits were measured using a fully standardized wavelength dispersive spectrometer mounted on a scanning electron microscope. In the co-doped state, the solubility limit of Ca in alumina was 32 ± 13 ppm, and the solubility limit of Mg in alumina was 210 ± 43 ppm. The presence of Ca results in an increase of the solubility limit of Mg in alumina from 132 to 210 ppm, suggesting that the increased Mg in solution results in more Mg excess at the alumina grain boundaries, thus contributing to a decreased grain-boundary mobility by solute-drag.     

Anticoagulant, Antioxidant and Antitumor Activities of Heterofucans from the Seaweed Dictyopteris delicatula

In the present study, six families of sulfated polysaccharides were obtained from seaweed Dictyopteris delicatula by proteolytic digestion, followed by acetone fractionation and molecular sieving on Sephadex G-100. Chemical analyses demonstrated that all polysaccharides contain heterofucans composed mainly of fucose, xylose, glucose, galactose, uronic acid, and sulfate. The fucans F0.5v and F0.7v at 1.0 mg/mL showed high ferric chelating activity (～45%), whereas fucans F1.3v (0.5 mg/mL) showed considerable reducing power, about 53.2% of the activity of vitamin C. The fucan F1.5v presented the most prominent anticoagulant activity. The best antiproliferative activity was found with fucans F1.3v and F0.7v. However, F1.3v activity was much higher than F0.7v inhibiting almost 100% of HeLa cell proliferation. These fucans have been selected for further studies on structural characterization as well as in vivo experiments, which are already in progress.     

Myo-InositolTrisPyroPhosphate treatment leads to HIF-1α suppression and eradication of early hepatoma tumors in rats

Myo-inositol trispyrophosphate (ITPP), a synthetic allosteric effector of hemoglobin, increases the regulated oxygen-releasing capacity of red blood cells (RBCs), leading to suppression of hypoxia-inducible factor 1α (HIF-1α) and to down-regulation of hypoxia-inducible genes such as vascular endothelial growth factor (VEGF). As a consequence, tumor growth is markedly affected. The effect of weekly intravenous injection of ITPP on an orthotopic, syngenic rat hepatocellular carcinoma (HCC) model was compared to that for untreated animals and animals subjected to conventional Doxorubicin chemotherapy. The longitudinal examination of HCC was performed by microCT imaging, and the cellular and molecular changes were evaluated by histology and Western blotting analysis of HIF-1α, VEGF, and caspase-3 gene expression in the tumor and in the surrounding liver. Hematologic impact was evaluated by blood cell-count measurement and determination of P50 (oxygen partial pressure for a 50 % oxygen saturation of hemoglobin). The HCC evaluation by microCT revealed a high potency of ITPP for tumor growth inhibition, thus allowing long-term survival and even cure of almost all the treated animals. The P50 value of hemoglobin in RBCs underwent a shift of 30 % following ITPP injection. Under these conditions, HIF-1α activity was strongly decreased, VEGF expression was down-regulated, and apoptosis was induced in HCC and surrounding liver cells, as indicated by Caspase-3 expression. ITPP did not affect hematologic parameters during treatment. The observations of in vivo tumor eradication suggest a significant clinical potential for ITPP in cancer therapy.     

Hydrothermal degradation of adsorbed sulfur mustard on activated carbon

Thermal and hydrothermal degradations of adsorbed sulfur mustard (HD) on activated carbon particles from a chemical protective over-garment were studied. Carbon loaded with 5 wt.% HD was heated in a closed reactor at temperatures up to 160 °C for 0.5–6 h and analyzed by solid-state ¹³C MAS NMR. On dry carbon at room temperature, HD was stable for months. On a thoroughly pre-wetted carbon, adsorbed HD partially degraded to thiodiglycol (TDG) and TDG-sulfoxide (TDG-SO) within 2–3 months. Heating dry HD-loaded carbon to 160 °C caused partial degradation within 4 h to 1,4-thioxane, along with 1,4-dithiane and vinyl sulfides. Complete degradation within 2.5 h to the same products occurred upon hydrothermal treatment of the HD-loaded carbon, using a water/carbon ratio of 0.3:1. With higher water/carbon ratios of 0.6:1–5:1 at temperatures of 120 °C and above, adsorbed HD hydrolyzed rapidly within 0.5 h. The latter reaction led to the formation of TDG concurrent with either thioxane (at 160 °C) or TDG-SO and TDG-dimer (at 120 °C). The mechanisms of the observed degradation processes are discussed.     

Chemoenzymatic Total Synthesis of Sorbicatechol Structural Analogues and Evaluation of Their Antiviral Potential

Sorbicillinoids are fungal polyketides characterized by highly complex and diverse molecular structures, with considerable stereochemical intricacy combined with a high degree of oxygenation. Many sorbicillinoids possess promising biological activities. An interesting member of this natural product family is sorbicatechol A, which is reported to have antiviral activity, particularly against influenza A virus (H1N1). Through a straightforward, one-pot chemoenzymatic approach with recently developed oxidoreductase SorbC, the characteristic bicyclo[2.2.2]octane core of sorbicatechol is structurally diversified by variation of its natural 2-methoxyphenol substituent. This facilitates the preparation of a focused library of structural analogues bearing substituted aromatic systems, alkanes, heterocycles, and ethers. Fast access to this structural diversity provides an opportunity to explore the antiviral potential of the sorbicatechol family.     

Induction of Systemic Acquired Resistance in Cotton Foliage Does Not Adversely Affect the Performance of an Entomopathogen

Baculoviral efficacy against lepidopteran larvae is substantially impacted by the host plant. Here, we characterized how baculoviral pathogenicity to cotton-fed Heliothis virescens larvae is affected by induction of systemic acquired resistance (SAR). Numerous studies have shown that SAR induced by the plant elicitor benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) can protect against plant pathogens, but reports on the impacts of SAR on chewing herbivores or on natural enemies of herbivores are few. We found that BTH application significantly increased foliar peroxidase activity, condensed tannin levels, and total phenolic levels but did not alter dihydroxyphenolic levels. Consumption of BTH-treated foliage did not influence H. virescens pupal weight or larval mortality by the microbial control agent Autographa californica multiple nucleopolyhedrovirus any more than did consumption of untreated foliage. Thus, activation of SAR, although it did not protect the plant against a chewing herbivore, also did not reduce the effect of a natural enemy on a herbivore, indicating that SAR and microbial control agents may be compatible components of integrated pest management.     

Fracture behavior of solid electrolyte LATP material based on micro-pillar splitting method

The NASICON type solid electrolyte LATP is a promising candidate for all-solid-state Li-ion batteries considering energy density and safety aspects. To ensure the performance and reliability of batteries, crack initiation and propagation within the electrolyte need to be suppressed, which requires knowledge of the fracture characteristics. In the current work, micro-pillar splitting was applied to determine the fracture toughness of LATP material for different grain orientations. The results are compared with data obtained using a conventional Vickers indentation fracture (VIF) approach. The fracture toughness obtained via micro-pillar splitting test is 0.89 ± 0.13 MPa?m^1/2, which is comparable to the VIF result, and grain orientation has no significant effect on the intrinsic fracture toughness. Being a brittle ceramic material, the effect of pre-existing defects on the toughness needs to be considered.