Established Liposome-Coated IMB16-4 Polymeric Nanoparticles (LNPs) for Increasing Cellular Uptake and Anti-Fibrotic Effects In Vitro

As a global health problem, liver fibrosis still does not have approved treatment. It was proved that N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamide) benzamide (IMB16-4) has anti-hepatic fibrosis activity. However, IMB16-4 displays poor water solubility and poor bioavailability. We are devoted to developing biodegraded liposome-coated polymeric nanoparticles (LNPs) as IMB16-4 delivery systems for improving aqueous solubility, cellular uptake, and anti-fibrotic effects. The physical states of IMB16-4−LNPs were analyzed using a transmission electron microscope (TEM), high-performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and differential scanning calorimeter (DSC). The results show that IMB16-4−LNPs increased the drug loading compared to liposomes and enhanced cellular uptake behavior compared with IMB16-4−NPs. In addition, IMB16-4−LNPs could repress the expression of hepatic fibrogenesis-associated proteins, indicating that IMB16-4−LNPs exhibited evident anti-fibrotic effects.     

Nano-Structured Ridged Micro-Filaments (≥100 µm Diameter) Produced Using a Single Step Strategy for Improved Bone Cell Adhesion and Proliferation in Textile Scaffolds

Textile scaffolds that are either 2D or 3D with tunable shapes and pore sizes can be made through textile processing (weaving, knitting, braiding, nonwovens) using microfilaments. However, these filaments lack nano-topographical features to improve bone cell adhesion and proliferation. Moreover, the diameter of such filaments should be higher than that used for classical textiles (10–30 µm) to enable adhesion and the efficient spreading of the osteoblast cell (>30 µm diameter). We report, for the first time, the fabrication of biodegradable nanostructured cylindrical PLLA (poly-L-Lactic acid) microfilaments of diameters 100 µm and 230 µm, using a single step melt-spinning process for straightforward integration of nano-scale ridge-like structures oriented in the fiber length direction. Appropriate drawing speed and temperature used during the filament spinning allowed for the creation of instabilities giving rise to nanofibrillar ridges, as observed by AFM (Atomic Force Microscopy). These micro-filaments were hydrophobic, and had reduced crystallinity and mechanical strength, but could still be processed into 2D/3D textile scaffolds of various shapes. Biological tests carried out on the woven scaffolds made from these nano-structured micro filaments showed excellent human bone cell MG 63 adhesion and proliferation, better than on smooth 30 µm- diameter fibers. Elongated filopodia of the osteoblast, intimately anchored to the nano-structured filaments, was observed. The filaments also induced in vitro osteogenic expression, as shown by the expression of osteocalcin and bone sialoprotein after 21 days of culture. This work deals with the fabrication of a new generation of nano-structured micro-filament for use as scaffolds of different shapes suited for bone cell engineering.     

Synthesis and Anti-Neuroinflammatory Activity of 1,7-diphenyl-1,4-heptadien-3-ones in LPS-Stimulated BV2 Microglia Via Inhibiting NF-κB/MAPK Signaling Pathways

A series of 1,7-diphenyl-1,4-heptadien-3-ones with various substituents (HO-, CH₃O-, CH₃-, Cl-) on the phenyl rings were synthesized and evaluated for anti-neuroinflammatory effects in LPS-stimulated BV2 microglia. The pharmacological results showed that the target compounds bearing methoxy groups greatly inhibited LPS-induced NO release, and that the active compounds CU-19 and CU-21 reduced the level of NO, TNF-α, IL-6 and PGE-2, downregulated the expression of COX-2 and iNOS in LPS-stimulated BV2 cells. A study of the mechanism of action revealed that CU-19 and CU-21 inhibited the nuclear translocation of NF-κB and phosphorylation of MAPKs (ERK, JNK, and p38). A preliminary pharmacokinetic study in rats revealed that the pharmacokinetic properties of CU-19 and CU-21 were dramatically ameliorated in comparison with the pharmacokinetic properties of curcumin.     

Synthesis of Cobalt Bis(Dicarbollide)—Curcumin Conjugates for Potential Use in Boron Neutron Capture Therapy

A series of novel cobalt bis(dicarbollide)—curcumin conjugates were synthesized. Two conjugates were obtained through the nucleophilic ring-opening reaction of the 1,4-dioxane and tetrahydropyran derivatives of cobalt bis(dicarbollide) with the OH group of curcumin, and using two equiv. of the oxonium derivatives, two other conjugates containing two cobalt bis(dicarbollide) units per molecule were obtained. In contrast to curcumin, the conjugates obtained were found to be non-cytotoxic against both tumor and normal cell lines. The analysis of the intracellular accumulation of the conjugates by flow cytometry showed that all cobalt bis(dicarbollide)—curcumin conjugates entered HCT116 colorectal carcinoma cells in a time-dependent manner. New non-cytotoxic conjugates contain a large amount of boron atoms in the biomolecule and can potentially be used for further biological research into boron neutron capture therapy (BNCT).     

Antioxidant Activity of Ruthenium Cyclopentadienyl Complexes Bearing Succinimidato and Phthalimidato Ligands

In these studies, we investigated the antioxidant activity of three ruthenium cyclopentadienyl complexes bearing different imidato ligands: (η⁵-cyclopentadienyl)Ru(CO)₂-N-methoxysuccinimidato (1), (η⁵-cyclopentadienyl)Ru(CO)₂-N-ethoxysuccinimidato (2), and (η⁵-cyclopentadienyl)Ru(CO)₂-N-phthalimidato (3). We studied the effects of ruthenium complexes 1–3 at a low concentration of 50 µM on the viability and the cell cycle of peripheral blood mononuclear cells (PBMCs) and HL-60 leukemic cells exposed to oxidative stress induced by hydrogen peroxide (H₂O₂). Moreover, we examined the influence of these complexes on DNA oxidative damage, the level of reactive oxygen species (ROS), and superoxide dismutase (SOD) activity. We have observed that ruthenium complexes 1–3 increase the viability of both normal and cancer cells decreased by H₂O₂ and also alter the HL-60 cell cycle arrested by H₂O₂ in the sub-G1 phase. In addition, we have shown that ruthenium complexes reduce the levels of ROS and oxidative DNA damage in both cell types. They also restore SOD activity reduced by H₂O₂. Our results indicate that ruthenium complexes 1–3 bearing succinimidato and phthalimidato ligands have antioxidant activity without cytotoxic effect at low concentrations. For this reason, the ruthenium complexes studied by us should be considered interesting molecules with clinical potential that require further detailed research.     

Increase in the Intracellular Bulk Water Content in the Early Phase of Cell Death of Keratinocytes,Corneoptosis, as Revealed by 65 GHz Near-Field CMOS Dielectric Sensor

While bulk water and hydration water coexist in cells to support the expression of biological macromolecules, how the dynamics of water molecules, which have long been only a minor role in molecular biology research, relate to changes in cellular states such as cell death has hardly been explored so far due to the lack of evaluation techniques. In this study, we developed a high-precision measurement system that can discriminate bulk water content changes of ±0.02% (0.2 mg/cm³) with single-cell-level spatial resolution based on a near-field CMOS dielectric sensor operating at 65 GHz. We applied this system to evaluate the temporal changes in the bulk water content during the cell death process of keratinocytes, called corneoptosis, using isolated SG1 (first layer of stratum granulosum) cells in vitro. A significant irreversible increase in the bulk water content was observed approximately 1 h before membrane disruption during corneoptosis, which starts with cytoplasmic high Ca²⁺ signal. These findings suggest that the calcium flux may have a role in triggering the increase in the bulk water content in SG1 cells. Thus, our near-field CMOS dielectric sensor provides a valuable tool to dissect the involvement of water molecules in the various events that occur in the cell.     

Wafer thickness optimization for silicon solar cells of heterogeneous material quality

In this Letter, we introduce a method of calculating the optimal wafer thickness for silicon solar cells with multicrystalline bulk material. The optimal thickness depends on the relation of bulk recombination to surface recombination and the light trapping. For multicrystalline silicon bulk recombination strongly varies laterally and with injection level, which complicates the calculations. A thickness optimization using the “Efficiency Limiting Bulk Recombination Analysis” (ELBA) takes all these effects correctly into account. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Synthesis and characterization of polythiophene block copolymer and fullerene derivative capable of “three‐point” complementary hydrogen bonding interactions and their application in bulk‐heterojunction solar cells

We report the synthesis and characterization of a polythiophene block copolymer (P4) selectively functionalized with diaminopyrimidine moieties and a thymine tethered fullerene derivative (F1). Self‐assembly between P4 and F1 through “three‐point” complementary hydrogen bonding is studied by ¹H NMR spectroscopy and differential scanning calorimetry. A large Stern‐Volmer constant (K_SV) of 1.2 × 10⁵ M^?1 is observed from fluorescence quenching experiments, revealing strong complexation between these two components. Solar cells employing P4 and F1 at different weight ratios as active layers are fabricated and tested; corresponding thin film morphologies are studied in detail by optical imaging and atomic force microscopy. Correlations between polymer complex structures, film morphologies, and device performance are discussed. Thermal stability of benchmark poly(3‐hexylthiophene) bulk heterojunction solar cells is found to be improved by the addition of a few weight percent of P4/F1 complexes as compatibilizers. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 3339–3350     

Multivalency as a Chemical Organization and Action Principle

Multivalent interactions can be applied universally for a targeted strengthening of an interaction between different interfaces or molecules. The binding partners form cooperative, multiple receptor–ligand interactions that are based on individually weak, noncovalent bonds and are thus generally reversible. Hence, multi‐ and polyvalent interactions play a decisive role in biological systems for recognition, adhesion, and signal processes. The scientific and practical realization of this principle will be demonstrated by the development of simple artificial and theoretical models, from natural systems to functional, application‐oriented systems. In a systematic review of scaffold architectures, the underlying effects and control options will be demonstrated, and suggestions will be given for designing effective multivalent binding systems, as well as for polyvalent therapeutics.     

Hydrophobic Vitamin B12. X. Steric Effect in Electrochemical Carbon-Skeleton Rearrangement Catalyzed by Hydrophobic Vitamin B12 in Nonaqueous Media

Abstract

A steric effect in the carbon-skeleton rearrangement catalyzed by heptamethyl cobyrinate perchlorate, [Cob(II)7C₁ester]C10₄, was investigated under electrochemical conditions. The controlled-potential electrolyses of alkyl halides having two carboxylic ester groups of different bulkiness on the same carbon atom, such as 2,2-bis(ethoxycarbonyl)-l-bromopropane, l-bromo-2-tert-butoxycarbonyl-2-ethoxy-carbonylpropane, l-bromo-2-cyclohexyloxycarbonyl-2-ethoxycarbonylpropane, and l-bromo-2-ethoxy-carbonyl-2-phenoxycarbonylpropane, were carried out in N,N-dimethylformamide, as catalyzed by [Cob(II)7C₁ester]CIO₄, to give the corresponding ester-migrated products in the dark at—1.5 V vs SCE in the presence of acetic acid and at—2.0 V vs SCE without acetic acid. As regards a correlation between bulkiness of an ester group and a migration aptitude, a smaller ester group tends to migrate to the adjacent carbon atom more readily than a larger one. The origin of such a steric effect is discussed with attention to the rate-determining step.