Search

Introduction: Lenvatinib and sorafenib are key therapeutic agents for hepatocellular carcinoma (HCC). However, there are no useful biomarkers for selecting molecular-targeted agents (MTAs). Skeletal muscle volume is associated with the clinical outcomes in these patients. We investigated the effects of lenvatinib and sorafenib on the skeletal muscles of patients with HCC., Methods: We evaluated the impact of skeletal muscle changes over a 3-month period for each MTA (n = 117; lenvatinib/sorafenib, 45/72). The skeletal muscle mass index (SMI) was measured at the third lumbar vertebra. Furthermore, we evaluated the direct effect of each MTA on primary human skeletal muscle cells by estimating muscle protein synthesis using western blot analysis., Results: The median change in SMI was -0.7% (p = 0.959) and -5.9% (p < 0.001) for the lenvatinib and sorafenib groups, respectively. Sorafenib had a greater effect on skeletal muscle loss than lenvatinib (p < 0.001). Additionally, SMI significantly decreased in the sorafenib group regardless of initial skeletal muscle volume (p < 0.001), whereas no significant differences were observed in the lenvatinib group. Sorafenib therapy (odds ratio [OR], 2.98; p = 0.023) and non-muscle depletion (OR, 3.31; p = 0.009) were associated with a decreased SMI. In vitro analysis showed that sorafenib negatively affected muscle synthesis compared to lenvatinib., Conclusions: Sorafenib may have a more negative effect on skeletal muscle than lenvatinib., (© 2024 S. Karger AG, Basel.)

A catalyst in the form of a capsule catalyst was prepared by coating HZSM5 membrane on a preshaped Co/SiO2 catalyst pellet. The capsule catalyst with HZSM5 membrane exhibited excellent selectivity for light hydrocarbon synthesis, especially for isoparaffin synthesis from syngas (CO + H2). Long-chain hydrocarbon formation was totally suppressed by the zeolite membrane. The modification of membrane and core catalyst significantly improved the catalytic properties of these new kinds of capsule catalysts.

A novel intracellular pH-sensitive polymeric micelle drug carrier that controls the systemic, local, and subcellular distributions of pharmacologically active drugs has been developed in this study. The micelles were prepared from self-assembling amphiphilic block copolymers, poly(ethylene glycol)-poly(aspartate hydrazone adriamycin), in which the anticancer drug, adriamycin, was conjugated to the hydrophobic segments through acid-sensitive hydrazone linkers. By this polymer design, the micelles can stably preserve drugs under physiological conditions (pH 7.4) and selectively release them by sensing the intracellular pH decrease in endosomes and lysosomes (pH 5−6). In vitro and in vivo studies show that the micelles have the characteristic properties, such as an intracellular pH-triggered drug release capability, tumor-infiltrating permeability, and effective antitumor activity with extremely low toxicity. The acquired experimental data clearly elucidate that the optimization of both the functional and structural features of polymeric micelles provides a promising formulation not only for the development of intracellular environment-sensitive supramolecular devices for cancer therapeutic applications but also for the future treatment of intractable cancers with limited vasculature.

An acetal-poly(ethylene glycol)-poly(2-(dimethylamino)ethyl methacrylate) (acetal-PEG-PAMA) block copolymer spontaneously associated with plasmid DNA (pDNA) to form water-soluble complexes (polyion complex micelle:  PIC micelle) in aqueous solution. Physicochemical characteristics and transfection efficiency of the PIC micelles thus prepared were studied here, focusing on the residual molar mixing ratio (N/P ratio) of AMA units in acetal-PEG-PAMA to the phosphate units in pDNA. With the N/P ratio increasing to unity, acetal-PEG-PAMA cooperatively formed complex micelles with pDNA through electrostatic interaction, allowing pDNA to condense effectively. Dynamic light scattering measurements revealed that the PIC micelle at N/P ≥ 3 had a constant size of approximately 90−100 nm. Eventually, acetal-PEG-PAMA/pDNA micelles underwent no precipitation even after long-term storage for more than 1 month at all N/P ratios. The PIC micelles were stable even in the presence of excess polyanions, poly(vinyl sulfate), in contrast to polyplexes based on the PAMA homopolymer, yet this stabilization effect was highly dependent on the N/P ratio to reach a plateau at N/P = 3−4. This character may be attributed to the increased hydrophobicity in the vicinity of the complexed pDNA. Furthermore, the pDNA in the micelle was adequately protected from DNase I attack. The transfection ability of the PIC micelles toward 293 cells was remarkably enhanced with an increasing N/P ratio as high as 25. The ζ-potential of the micelles with a high N/P ratio was an appreciably large positive value, suggesting a noncooperative micelle formation. This deviated micellar composition with an excess cationic nature as well as the presence of free acetal-PEG-PAMA may play a substantial role in the enhanced transfection efficiency of the PIC micelle system in the high N/P ratio (~25) region.

Organically functionalized mesoporous silica films have been prepared by a novel synthetic procedure that involves spin-coating of mesostructured silica films and a vapor infiltration (VI) technique, using organosiloxanes, before the removal of surfactant. The VI-treated mesostructured films were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and a field emission scanning electron microscope (FE-SEM). Nitrogen adsorption/desorption measurements were performed using films attached with a silicon substrate. The XRD and FE-SEM measurements show that the mesochannel wall, densified and modified with organosilyl groups by the VI treatment, hardly contracts under calcination. FE-SEM observations for the films' cross section support the view that organosiloxane vapor is not deposited on the surface of the film. These results show that organosiloxane molecules penetrate the film and are selectively incorporated into the silica wall. Thus, hydrophobic mesoporous silica films can be synthesized without a reduction in pore size, a result that cannot be attained by conventional grafting and co-condensation methods. The excellent high porosity and hydrophobicity of the mesostructured composite films may be of advantage for next-generation low-k dielectric films.

Silicalite-1 coatings were synthesized on spherical Pt/TiO2 particles with a diameter of 0.5 mm from an aqueous solution of fumed silica, tetrapropylammonium hydroxide (TPAOH), and ethanol under hydrothermal conditions. SEM images show that the surface of the Pt/TiO2 particles was fully covered by intergrown silicalite-1 crystals with a crystal size of 5 × 2 × 15 μm. From the cross section of crushed silicalite/Pt/TiO2 particles, the estimated thickness of the silicalite-1 layer was about 40 μm. The compactness of the layer to act as a membrane was demonstrated by catalytic tests of the silicalite-1/Pt/TiO2 particles. The hydrogenation of a mixture of linear 1-hexene (1-Hex) and dibranched 3,3-dimethylbut-1-ene (3,3-DMB) (in a molar ratio of 1-Hex to 3,3-DMB of 1:1.68) was performed using a fixed-bed reactor with a continuous flow system. The composite silicalite-1/Pt/TiO2 catalyst showed 1-Hex/3,3-DMB hydrogenation selectivities of 12−20 at 50 °C and 18−30 at 100 °C due to the selective permeation of 1-Hex into the Pt/TiO2 particles through the silicalite-1 layer. Deactivation of the catalyst was also reduced, probably by protection against poisoning impurities in the feed. This work demonstrates the feasibility of the application of catalyst particles coated with a permselective membrane to achieve reactant selectivities on a particle level.

Cisplatin (CDDP)-incorporated polymeric micelles (CDDP/m) are a macromolecular carrier system possessing a time-modulated decaying property accompanied by sustained release of free drug. The gene expression profiles in nonsmall cell lung cancer PC-14 cells treated with free CDDP and CDDP/m were evaluated by a cDNA expression array for 807 genes. Although the total gene expression profile of the cells treated with CDDP/m approximated that of free CDDP in the hierarchical clustering analysis, a number of genes showed differential expression according to whether the cells had been treated with CDDP or CDDP/m. Ultimately, 50 genes with significant differential expression between cells treated with CDDP and CDDP/m were selected by principal component (PC) analysis and the unpaired t-test. The genes selected, including genes related to cell cycle regulation, apoptosis-related proteins, detoxification, and DNA repair enzymes, were considered to be related to CDDP-induced cytotoxicity. Interestingly, CDDP/m down-regulated the genes encoding integrins and matrix metalloproteinases (MMPs), which play an integral role in tumor invasion, metastasis, and angiogenesis, whereas free CDDP up-regulated them. The results suggest that use of the macromolecular carriers may yield additional therapeutic effects over free drug.

The light-harvesting dendrimer zinc porphyrin [NH2CH2CH2NHCO]32DPZn, a potential photosensitizer in photodynamic therapy, was synthesized and successfully assembled with poly(ethylene glycol)-b-poly(aspartic acid) to form micelles in PBS buffer (10 mM) following the concept of polyion complex micelle. The coupling reaction between the [CO2H]32DPZn and N-trifluoroacetylethylene-1,2-diamine using the DCC/HOBt method afforded the protected dendrimer [CF3CONHCH2CH2NHCO]32DPZn, which was then mildly hydrolyzed to remove all the trifluoroacetyl protecting groups. Light-scattering measurements showed that the [NH2CH2CH2NHCO]32DPZn has the ability to assemble with poly(ethylene glycol)-b-poly(aspartic acid) to form a spherical micelle with a diameter of about 55 nm, having a narrow size polydispersity in PBS. The micelles were stable both in size and composition up to a 0.90 M (NaCl) salt concentration. The high salt stability is associated with a hydrogen-bonding network formed in the micellar core among the amide groups of the dendrimers and those of poly(aspartic acid) moieties, which could be destroyed by urea, a typical hydrogen-bonding cleaver. Furthermore, the pH range for the stable micelles in physiological saline (0.15 M NaCl) is from 6.2 to 7.4, suggesting the potential of the pH-triggered release of the entrapped dendrimers in the acidic pH environment (pH ~ 5.0) of the intracellular endosomal compartment.

Nano-phase transition of an organic−inorganic nanocomposite under vapor infiltration of tetraethoxysilane (TEOS) or tetramethoxysilane (TMOS) was found in mesoporous thin film preparation. The rearrangement into a hexagonal periodic structure implies high mobility of the surfactant−silicate composites in solid phase. The swelling of film thickness and d spacing was observed under vapor infiltration. The nano-phase transition under vapor infiltration contains two competitive processes:  (1) the penetration of TEOS or TMOS into the film and (2) the reaction of the silanol group. Film thickness and d spacing were controlled by changing synthetic temperature, silica sources (TEOS and TMOS), catalysts (HCl and NH3), and the thickness of surfactant films. The films prepared from vapor phase show superior characteristics, such as high structural stability and high resistance to water adsorption. The vapor infiltration method is a simpler process than conventional sol−gel techniques and attractive for mass production of a variety of organic−inorganic composite materials and inorganic porous films.

Photodynamic therapy (PDT) is a promising therapeutic modality for treatment of solid tumors. In this study, third-generation aryl ether dendrimer porphyrins (DPs) with either 32 quaternary ammonium groups (32(+)DPZn) or 32 carboxylic groups (32(−)DPZn) were evaluated as a novel, supramolecular class of photosensitizers for PDT. DPs showed a different cell-association profile depending on the positive or negative charge on the periphery, and both DPs eventually localized in membrane-limited organelles. In contrast, protoporphyrin IX (PIX), which is a hydrophobic and relatively low molecular weight photosensitizer used as a control in this study, diffused through the cytoplasm except the nucleus. Confocal fluorescent imaging using organelle-specific dyes indicated that PIX induced severe photodamage to disrupt membranes and intracellular organelles, including the plasma membrane, mitochondrion, and lysosome. On the other hand, cells treated with DPs kept the characteristic fluorescent pattern of such organelles even after photoirradiation. However, notably 32(+)DPZn achieved remarkably higher ¹O2-induced cytotoxicity against LLC cells than PIX. Furthermore, both dendrimer porphyrins had far lower dark toxicity as compared with PIX, demonstrating their highly selective photosensitizing effect in combination with a reduced systemic toxicity.

A mesoporous silica film was prepared on a silicon substrate using a spin-coating process followed by a tetraethyl orthosilicate (TEOS) vapor treatment. The TEOS-treated mesostructured silica film did not contract during calcination, showing high structural stability. Thermal treatment without TEOS vapor was not effective to enhance the structural stability of mesostructured films. A flat mesoporous silica film about 250 nm thick was grown from the silicon substrate. No silica particle was deposited from TEOS vapor on the surface of the film, suggesting the penetration of TEOS vapor into the film. A periodic porous structure was observed in the FE-SEM image of the cross section of the mesostructured film. This indicates that the channels run predominantly parallel to the surface of the silicon substrate. FTIR studies suggested that the silanol groups in the film significantly decreased after the TEOS treatment. TEOS molecules penetrate into an originally deposited silicate film and react with the silanol groups. The densified silica wall has high structural stability and hardly contracts under a calcination process. The developed TEOS-treated mesoporous silica film is a promising material such as chemical sensors, low-k films, and other optoelectronic devices.

An MCM-48 membrane was prepared on a porous α-alumina support by hydrothermal synthesis. The silylation with trimethylsilane and triethylsilane was used to enhance hydrothermal stability and hydrophobicity of the MCM-48 membrane. The studies of X-ray diffraction, Fourier transform infrared (FTIR), nitrogen adsorption, and water adsorption were carried out using an MCM-48 powder to characterize the pore surface of MCM-48. The FTIR study indicates that the silyl group was substituted for the Si−OH group on the pore surface of MCM-48. The pore sizes of the nonsilylated and the silylated MCM-48 were 2.4 (nonsilylated), 1.9 (trimethylsilylated), and 1.8 nm (triethylsilylated). The water adsorption study showed that the pore surface of MCM-48 significantly changed to hydrophobic by silylation. The nonsilylated and the trimethylsilylated MCM-48 membranes were used for the separation of an ethanol/water mixture. The separation factor was 16 through the silylated membrane, although that of the nonsilylated membrane was 0.3, indicating that the pore of the silylated membrane hardly adsorbed water. Furthermore, the hydrothermal stability of the MCM-48 membrane was improved by the silylation.

A propagation model of cigarette static burn at the cigarette periphery is proposed. Propagation of cigarette static burn is characterized by intermittent burn of the cigarette paper. The burning rate depends on the period of flash burn of the paper and is independent of the burning width. By measuring the local temperature near the front line of the burning propagation, the rate-determining step was identified as the time required to ignite the paper. A mathematical analysis was performed by calculating the heat transfer at the periphery during the paper heating period, and it was revealed that the thermal properties of the cigarette are the dominant factors of cigarette static burn. Modeling results showed good agreement with measured data.

Core−shell type micelles with a hydrodynamic diameter of 52 nm composed of 38 molecules of zinc dendrimer porphyrin with 32 carboxylate groups on the periphery and 39 poly(ethylene glycol)−poly(l-lysine) (PEG−PLys) block copolymers were prepared at a stoichiometric mixing ratio. These micelles showed an unusually high stability against NaCl solutions due to the formation of hydrogen bonds at salt concentrations higher than 200 mM NaCl. In contrast, large aggregates of 250−300 nm diameter of a zinc dendrimer porphyrin were formed with 32 positively charged trimethylammonium groups and poly(ethylene glycol)−poly(aspartic acid) (PEG−PAsp) block copolymer. These aggregates lack the ability to form hydrogen bonds and almost completely dissociate at salt concentrations higher than 200 mM. Both polyion dendrimer micelle systems showed a high stability upon dilution with 150 mM NaCl without a critical association concentration being observed. Both polyion dendrimer micelle complexes have potential to be used as drug delivery systems for light-harvesting ionic zinc dendrimer porphyrin sensitizers.

Abstract: Determination of the phase boundary between ilmenite and perovskite structures in MgSiO3 has been made at pressures between 18 and 24 GPa and temperatures up to 2000 °C by in situ X-ray diffraction measurements using synchrotron radiation and quench experiments. It was difficult to precisely define the phase boundary by the present in situ X-ray observations, because the grain growth of ilmenite hindered the estimation of relative abundances of these phases. Moreover, the slow reaction kinetics between these two phases made it difficult to determine the phase boundary by changing pressure and temperature conditions during in situ X-ray diffraction measurements. Nevertheless, the phase boundary was well constrained by quench method with a pressure calibration based on the spinel-postspinel boundary of Mg2SiO4 determined by in situ X-ray experiments. This yielded the ilmenite-perovskite phase boundary of P (GPa) = 25.0 (±0.2) – 0.003 T (°C) for a temperature range of 1200–1800 °C, which is generally consistent with the results of the present in situ X-ray diffraction measurements within the uncertainty of ∼±0.5 GPa. The phase boundary thus determined between ilmenite and perovskite phases in MgSiO3 is slightly (∼0.5 GPa) lower than that of the spinel-postspinel transformation in Mg2SiO4.

The pervaporation tests for n-hexane, 2-methylpentane (2-MP), and 2,3-dimethylbutane (2,3-DMB) were performed using an MFI-type zeolitic membrane at 303 K. In the unary systems, those fluxes followed the order n-hexane ≫ monobranched hexane (2-MP), > dibranched hexane (2,3-DMB). The ideal selectivities of n-hexane/2-MP and n-hexane/2,3-DMB were 37 and 50, respectively. n-Hexane preferentially permeated in the measurements of a binary mixture of n-hexane/2-MP and n-hexane/2,3-DMB. The feed composition dependence in separating n-hexane/2,3-DMB binary mixtures was studied. The separation factor for the 50/50 n-hexane/2,3-DMB mixture exceeded 120, which was much greater than 54 in the 50/50 n-hexane/2-MP system. When the feed concentration of n-hexane was 10 mol %, the separation factor α(n-hexane/2,3-DMB) at the steady state was as high as 270. n-Hexane effectively inhibited the permeation of 2,3-DMB, even when the concentration of n-hexane was very small.

Block copolymer micelles (polymer−metal complex micelles) containing platinum(II) complexes in the core were prepared through the complexation of cis-dichlorodiammineplatinum(II) (cisplatin, CDDP) with poly(ethylene glycol)−poly(α,β-aspartic acid) block copolymer (PEG−P(Asp)) in an aqueous medium. Dynamic light scattering measurements revealed that CDDP-complexed micelles had diameters of approximately 20 nm with considerably narrow distribution. The critical substitution molar ratio of CDDP to Asp residues in PEG−P(Asp) (CDDP/Asp) to form a stable micelle structure was determined to be 0.5. The CDDP-complexed micelle, which was stable in distilled water at room temperature, started to dissociate in approximately 10 h of the induction period accompanying the sustained release of platinum(II) complex from the micelle in physiological saline (0.15 M NaCl solution) at 37 °C. The release rate of CDDP was inversely correlated with the chain length of P(Asp) segments in the block copolymer. This property of sustained CDDP release with modulated micelle dissociation leads to the potential utility of the CDDP-complexed micelle as a tumor-directed carrier system.

Not Available

Not Available

Rats with or without renal failure, produced by uranyl acetate, were subjected to water-immersion stress for 6 h. The severity of stress-induced gastric ulcers in the renal failure group was significantly higher than that in the control group. The intragastric pH did not significantly differ between the two groups. Transmucosal electrical potential difference, gastric mucosal blood flow, and gastric mucosal hexosamine content in the renal failure group were significantly lower than in the control group. These results suggest that decreases in defensive factors, rather than an increase in an aggressive factor, may be more closely involved in the development of acute gastric ulcers in rats with renal failure.

The ryanodine receptor type 3 (RyR-3) functions as a Ca2+-induced Ca2+ release (CICR) channel and is distributed in a wide variety of cell types including skeletal muscle and smooth muscle cells, neurons, and certain non-excitable cells. However, the physiological roles of RyR-3 are totally unclear. To gain an insight into the function of RyR-3 in vivo, we have generated mice lacking RyR-3 by means of the gene targeting technique. The mutant mice thus obtained showed apparently normal growth and reproduction. Although Ca2+-induced Ca2+ release from intracellular Ca2+ stores of the mutant skeletal muscle differed in Ca2+ sensitivity from that of wild-type muscle, excitation-contraction coupling of the mutant muscle seemed to be normal. Moreover, we could not find any significant disturbance in the smooth muscle and lymphocytes from the mutant mice. On the other hand, the mutant mice showed increased locomotor activity, which was about 2-fold greater than that of the control mice. These results indicate that the loss of RyR-3 causes no gross abnormalities and suggest that the lack of RyR-3-mediated Ca2+ signaling results in abnormalities of certain neurons in the central nervous system.