Focus on Extracellular Vesicles: Development of Extracellular Vesicle-Based Therapeutic Systems

Many types of cells release phospholipid membrane vesicles thought to play key roles in cell-cell communication, antigen presentation, and the spread of infectious agents. Extracellular vesicles (EVs) carry various proteins, messenger RNAs (mRNAs), and microRNAs (miRNAs), like a “message in a bottle” to cells in remote locations. The encapsulated molecules are protected from multiple types of degradative enzymes in body fluids, making EVs ideal for delivering drugs. This review presents an overview of the potential roles of EVs as natural drugs and novel drug-delivery systems.     

Synthesis of anatase TiO_2 with exposed {001} and {101} facets and photocatalytic activity

Anatase titanium(Ⅳ) oxide(TiO_2) particles with exposed {001} and {101} facets were prepared by hydrothermal treatment of amorphous TiO_2 with H_2O_2-NH_3 solution. Crystal phase, shape, and size of TiO_2 particles are found to be greatly dependent on the ratio of H_2O_2-NH_3 solution. The prepared TiO_2 particles with specific exposed crystal faces show higher photocatalytic activity for acetaldehyde decomposition than commercial spherical TiO_2 particles. This result implies that recombination is prevented by spatial separation of redox sites in the particles because of selective migration of electrons and positive holes to specific exposed crystal faces and/or different reactivity of electrons and positive holes on the specific exposed crystal face.     

The roles of the Trommsdorff–Norrish effect in phase separation of binary polymer mixtures induced by photopolymerization

Influence of the Trommsdorff–Norrish (T–N) effect on the phase separation of methyl methacrylate (MMA)/poly(ethyl acrylate) (PEA) mixtures undergoing photo-polymerization was examined by a combination of several experimental techniques. By FT-IR spectroscopy, it was found that the polymerization conversion explosively increases at the onset of this T–N effect. The characteristic irradiation time τ at which this effect occurs, strongly depends on the light intensity and gradually shifts to early time as the irradiation intensity increases. The shrinkage of the mixture observed in situ by laser-scanning confocal microscopy exhibits a transition at a particular irradiation time which is slightly longer than the characteristic time τ. By gel permeation chromatography (GPC), it was found that the molecular weight of the resulting PMMA was almost unchanged before τ and suddenly increases about an order of magnitude after the onset of the auto-acceleration effect. Finally, the characteristic length scales of the morphology also quickly increase with irradiation time and are eventually frozen by this T–N effect. These experimental results indicate that the Trommsdorff–Norrish effect plays an important role in the kinetic processes of polymerization-induced phase separation, suggesting an efficient tool to control the morphology of the polymerizing mixture.     

Chain stiffness and chain conformation of poly(α-methylene-γ-butyrolactone) in dilute solutions

The chain stiffness and local chain conformation of atactic poly(α-methylene-γ-butyrolactone) (PMBL), which is a side chain cyclic structural analog of poly(methyl methacrylate) (PMMA), with a weight-average molecular weight (M_w) ranging from 2.8 × 10³ to 2.6 × 10⁶ in N,N-dimethylformamide (DMF) and γ-butyrolactone (GBL) were characterized by size exclusion chromatography with a multi-angle light-scattering detector (SEC-MALS) and synchrotron radiation small-angle X-ray scattering (SAXS). Based on the Kratky-Porod worm-like chain model, the scattering functions and the M_w dependence of z-average root-mean-square radius of gyration <S²>_z^1/2 yielded the Kuhn segment lengths λ⁻¹, the diameter of the PMBL chains d, and the excluded-volume strengths in DMF and GBL. The local conformation of atactic PMBL in DMF and GBL were slightly larger than those of atactic PMMA, due to the presence of the conformationally rigid lactone ring structure.     

Molecular Hydrogen Enhances Proliferation of Cancer Cells That Exhibit Potent Mitochondrial Unfolded Protein Response

Molecular hydrogen ameliorates pathological states in a variety of human diseases, animal models, and cell models, but the effects of hydrogen on cancer have been rarely reported. In addition, the molecular mechanisms underlying the effects of hydrogen remain mostly unelucidated. We found that hydrogen enhances proliferation of four out of seven human cancer cell lines (the responders). The proliferation-promoting effects were not correlated with basal levels of cellular reactive oxygen species. Expression profiling of the seven cells showed that the responders have higher gene expression of mitochondrial electron transport chain (ETC) molecules than the non-responders. In addition, the responders have higher mitochondrial mass, higher mitochondrial superoxide, higher mitochondrial membrane potential, and higher mitochondrial spare respiratory capacity than the non-responders. In the responders, hydrogen provoked mitochondrial unfolded protein response (mtUPR). Suppression of cell proliferation by rotenone, an inhibitor of mitochondrial ETC complex I, was rescued by hydrogen in the responders. Hydrogen triggers mtUPR and induces cell proliferation in cancer cells that have high basal and spare mitochondrial ETC activities.     

Mutation Analysis of Radioresistant Early-Stage Cervical Cancer

Radiotherapy is a definitive treatment for early-stage cervical cancer; however, a subset of this disease recurs locally, necessitating establishment of predictive biomarkers and treatment strategies. To address this issue, we performed gene panel-based sequencing of 18 stage IB cervical cancers treated with definitive radiotherapy, including two cases of local recurrence, followed by in vitro and in silico analyses. Simultaneous mutations in KRAS and SMAD4 (KRAS^mt/SMAD4^mt) were detected only in a local recurrence case, indicating potential association of this mutation signature with radioresistance. In isogenic cell-based experiments, a combination of activating KRAS mutation and SMAD4 deficiency led to X-ray resistance, whereas either of these factors alone did not. Analysis of genomic data from 55,308 cancers showed a significant trend toward co-occurrence of mutations in KRAS and SMAD4. Gene Set Enrichment Analysis of the Cancer Cell Line Encyclopedia dataset suggested upregulation of the pathways involved in epithelial mesenchymal transition and inflammatory responses in KRAS^mt/SMAD4^mt cancer cells. Notably, irradiation with therapeutic carbon ions led to robust killing of X-ray-resistant KRAS^mt/SMAD4^mt cancer cells. These data indicate that the KRAS^mt/SMAD4^mt signature is a potential predictor of radioresistance, and that carbon ion radiotherapy is a potential option to treat early-stage cervical cancers with the KRAS^mt/SMAD4^mt signature.     

Interactive visualization of three-dimensional magnetic fields

In order to observe the physical values (magnetic flux density and eddy current) in 3D magnetic field analysis, an interactive and highly manipulative visualization system depicting stereo images is intalled in a graphics workstation with high functional graphic processors. The system has the following characteristics:

• 1 An interactive and highly manipulative menu window with many functions: it enables visualization of complex phenomena in a 3D field through observation of various combinations of physical values from various viewpoints.
• 2 Simultaneous display of both magnetic flux density and eddy current by using the appropriate use of two colour display methods for stream lines and distribution maps of density: this function facilitates observation of the mutual relations between two physical values in a 3D field.
• 3 Animations and stereo displays: since they give extremely distinct images, observers can easily understand even highly complex 3D phenomena.

In this paper, the calculation method of density vectors, their display methods, and interactive functions are described. Some examples are also illustrated.     

Steam Reforming of Methanol on Copper Catalysts Supported on Large-Surface-Area ZnAl2O3

Steam reforming of methanol on various supported Cu catalysts was examined. Supports strongly affected catalyst activity and, among the catalysts tested, Cu catalyst supported on large-surface-area ZnAl₂O₄ showed the highest activity, which, to the best of our knowledge, was higher than those for the supported catalysts reported so far. For supported Cu catalysts, two species were observed. One was a dispersed Cu species having strong interaction between Cu and support, and the other was an isolated Cu species. The activity of the former species strongly depended on supports.     

Chain matching between hydrocarbon and fatty acid as interfacial phenomena

According to the investigations of Cameron and his coworkers^1–5 into the chain-matching phenomena between normal paraffin as a solvent and straight-chain fatty acid as an additive, the optimum condition in boundary lubrication is attained when the chain lengths of the additive and solvent are equal. A series of experiments has been conducted over the past ten years on the role of the chain-matching effect, not only on boundary lubrication but also widely on relevant interfacial phenomena. The results of the investigations are discussed.     

Investigation of radiation-induced surface activation effect in austenitic stainless steel under ultraviolet and γ-ray irradiations

The radiation-induced surface activation (RISA) effect will be applied to the core design in supercritical light water reactor (SCWR) in order to achieve a high performance with excellent economy and safety. The purpose of the present study is to investigate the RISA effect in the candidate fuel cladding materials in SCWR such as PNC1520. The change of weldability due to RISA effect and the related microstructure analysis were performed in oxidized PNC1520 and 304 stainless steel with various oxidization periods. The phases contained in the surface oxide layer of the present specimen were identified as Fe₂CrO₄, γ-Fe₂O₃, and Fe₂O₃. The lifetime of 13.8 days for wettability improving factor was confirmed in the ultraviolet (UV) irradiation. Meanwhile, the long life of 13.8 days and short life of 0.8 days for wettability improving factors were identified in the γ-ray irradiation. Based on the fact that the band gap energies of Fe₂CrO₄, γ-Fe₂O₃, and Fe₂O₃ were, respectively, 2.1, 2.0, and 2.2 eV, and the photo energies of UV and γ-ray irradiation were 4.48 eV and 13.3 MeV, it is therefore clarified that the hydrophilization on the oxide layer is ascribed to the RISA effect.