The preparation and characterization of ferrocene containing hexacatenar metallomesogens 4a-h based on alkoxy terminal groups with hexyloxy (4a), octyloxy (4b), decyloxy (4c), dodecyloxy (4d), tetradecyloxy (4e), hexadecyloxy (4f), octadecyloxy (4g) and eicosyloxy (4h) chains are described. The introduction of alkyl chains of different lengths induces a rich variety of self-assembled liquid crystalline structures. In the crystalline state, the ferrocene containing hexacatenar metallomesogens 4a-h organize into a microphase-separated monolayer lamellar structure. In contrast, a dramatic phase change after crystalline melting of the metallomesogens is observed with variation of the chain length. The ferrocene containing hexacatenar metallomesogens 4b and c display a bicontinuous cubic mesophase with Ia3d symmetry, while the ferrocene containing hexacatenar metallomesogens 4d-g exhibit a hexagonal columnar mesophase. Further increasing the length of the alkyl chain as in the case of 4h suppresses liquid crystallinity and induces only a crystalline phase. This unique behavior in the ferrocene containing metallomesogenic molecules can be understood to originate from the anisotropic aggregation of ferrocene containing aromatic segments and consequent entropic penalties associated with chain stretching.
Gene therapy using RNA interference can be directed against tumors through various strategies, but has been hindered owing to the inefficiency of non-viral delivery. To evaluate the antitumor effects of adenine nucleotide translocase-2 (ANT2) short hairpin RNA (shRNA) by intraperitoneal injection using the polyethylenimine (PEI) and an ultrasound gene delivery method, human breast carcinoma MDA-MB-231 cells were injected subcutaneously into NOG (NOD/Shi-scid/IL-2Rγ(null)) mice. The results showed greater tumor regression (*P<0.05) as well as an increased survival rate in the group receiving ANT2 shRNA+two types of enhancer relative to the groups receiving ANT2 shRNA without enhancer. These findings demonstrate that the introduction of PEI and ultrasound with SonoVue exerted enhanced antitumor effects in vivo. Although the combination of jet-PEI and ultrasound provided the best results with respect to tumor regression, the antitumor effects from the individual enhancers were approximately equivalent. In addition, we confirmed that there was no toxicity on aspartate aminotransferase and alanine aminotransferase levels in the liver and albumin, blood urea nitrogen or creatine kinase levels in the kidney following the various gene delivery methods.
This study evaluated the possible clinical application of low-intensity ultrasound (LIUS) stimulation for preventing osteoporotic bone fracture. Eight virgin 14-week-old ICR mice (weight 24.0 +/- 0.7 g) were ovariectomized to induce osteoporosis. The right hind limbs (US limbs) were stimulated with LIUS, whereas the left hind limbs (CON limbs) were not stimulated. LIUS was applied for 20 min a day, 5 days a week over a 6-week period using the following parameters: 1.5 MHz frequency, 1.0 kHz pulse repetition, 30 mW/cm(2) intensity, and 200 mus pulse length. The effective structural modulus increased significantly (p < 0.05) in the US limbs over time with the increased bone quantity, whereas that in CON limbs remained statistically constant (p > 0.05). In addition, the elastic modulus in the US limbs was generally enhanced by an increased bone quality, compared with the CON limbs. Therefore, LIUS stimulation may effectively reduce the risk of osteoporotic bone fracture by increasing the mechanical characteristics of bone via improvements in both the effective structural and elastic modulus of the osteoporotic bone. In conclusion, LIUS may potentially prove very effective clinically for preventing osteoporotic bone fractures.
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