Extracorporeal cardiac shock wave therapy for ischemic heart disease

Prognosis of severe ischemic heart disease with no indication of percutaneous coronary intervention or coronary artery bypass grafting still remains poor. Extracorporeal shock wave therapy was introduced for medical therapy more than 20 years ago to break up kidney stones. We have demonstrated that extracorporeal cardiac shock wave therapy at a low level of ~10% of energy density that used for urinary lithotripsy treatment, effectively induces coronary angiogenesis and improves myocardial ischemia in a porcine model of chronic myocardial ischemia in vivo. On the basis of the promising results in animal studies, we have recently developed a new, non-invasive angiogenic therapy with low-energy shock waves for ischemic heart disease. Our extracorporeal cardiac shock wave therapy improved symptoms and myocardial ischemia in patients with severe coronary artery disease. These beneficial effects of the shock wave therapy persisted for at least 12 months. Importantly, no procedural complications or adverse effects were noted. These results indicate that our extracorporeal cardiac shock wave therapy is an effective and non-invasive treatment for ischemic heart disease. To further confirm the usefulness and safety of our SW therapy, we are currently conducting the second clinical trial in a randomized and placebo-controlled manner.      

Rhenium complex-catalyzed acylative cleavage of ethers with acyl chlorides

It was found that rhenium complex was an efficient catalyst for the acylative cleavage of C-O bond of ethers with acyl chlorides. When acyclic ethers were allowed to react with acyl chlorides in the presence of a catalytic amount of ReBr(CO)₅, acylative cleavage of C-O bond of acyclic ethers smoothly proceeded to give the corresponding esters in moderate to good yields. Similarly, cyclic ethers were acylative cleaved by acyl chlorides to give the corresponding chloro substituted esters in good yields by the use of Re₂O₇ catalyst.     

Image printing on the surface of anti-biofouling zwitterionic polymer brushes by ion beam irradiation

A CMB monomer was polymerized on a glass plate with a surface-confined ATRP initiator containing a 2-bromoisobutyryl group. The glass plate modified with a PCMB brush was highly hydrophilic and showed a strong resistance against non-specific adsorption of proteins and cell adhesion. Upon ion beam irradiation, furthermore, the PCMB brush was ablated and a hollow space with a designed shape could be made to which HEK293 cells (from human embryonic kidney) and Hep G2 (from human hepatoma) cells non-specifically adhered, while no adhesion of these cells to the non-treated area on the brush was observed. The present results clearly indicate the usefulness of ion beam-printed patterns of anti-biofouling zwitterionic polymer brushes in the biomedical field.     

Pattern enrichment analysis for phage selection of stapled peptide ligands

Phage display is the most widely used technique to discover de novo peptides that bind to target proteins. However, it is associated with some challenges such as compositional bias. In this study, to overcome these difficulties, we devised a ‘pattern enrichment analysis.’ In this method, two samples (one obtained by affinity selection, the other simply amplified without selection) are prepared, and the two sequence datasets read on next-generation sequencer are compared to find the three-residue pattern most enriched in the selected sample. This allows us to compare two sequence datasets with high coverage and facilitates the identification of peptide sequences and the key residues for binding. We also demonstrated that this approach in the combination with structured peptide libraries allowed spatial mapping of the enriched sequence patterns. Here, we prepared a phage library displaying chemically stapled helical peptides with the X₁C₂X₃X₄X₅X₆X₇X₈C₉X₁₀ sequence, where X is any amino acid. To validate our method, we performed screening against the HDM2 protein. The results showed that the hydrophobic residues (Phe, Tyr, Trp and Leu) that are key to interactions with HDM2 were clearly identified by the pattern enrichment analysis. We also performed selection targeting the SARS-CoV-2 spike RBD in the same manner. The results showed that similar patterns were enriched among the hit peptides that inhibited the protein–protein interaction.

To effectively identify helical peptide binders from a phage library, we developed “pattern enrichment analysis,” which finds the enriched three-residue patterns by comparison with a control sample.     

Structural study of NO adsorbed on the reconstructed Pt(110)-(1 x 2) surface with X-ray photoelectron diffraction and near-edge X-ray absorption fine structure spectroscopy

The adsorption structure of NO on the reconstructed Pt(110)-(1 x 2) surface was studied with X-ray photoelectron spectroscopy (XPS), X-ray photoelectron diffraction (XPD), low-energy scanned-angle photoelectron diffraction (LESA-PD), and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy. The experiments were performed at 180 K, where no surface lifting from (1 x 2) to (1 x 1) takes place after NO adsorption. XPS indicates that the (1 x 2) unit cell of the Pt(110) surface contains 1.5 NO molecules at the saturated coverage. XPD and LESA-PD analyses allow us to propose a structural model for the NO adlayer, where two-thirds of the NO molecules in the (1 x 2) unit cell are adsorbed on the atop site of the close-packed Pt rows (ridges) along the [10] direction with an inclined geometry and one-third of the NO molecules adsorb on the bridge site between the Pt ridges with an upright configuration. This model is supported by the N K-edge NEXAFS experiments and is consistent with the recently reported model based on the density functional theory (Orita, H.; Nakamura, I.; Fujitani, T. J. Phys. Chem. B 2005, 109, 10312).     

Differences in dual-task performance and prefrontal cortex activation between younger and older adults

Background

The purpose of this study was to examine task-related changes in prefrontal cortex (PFC) activity during a dual-task in both healthy young and older adults and compare patterns of activation between the age groups. We also sought to determine whether brain activation during a dual-task relates to executive/attentional function and how measured factors associated with both of these functions vary between older and younger adults.

Results

Thirty-five healthy volunteers (20 young and 15 elderly) participated in this study. Near-infrared spectroscopy (NIRS) was employed to measure PFC activation during a single-task (performing calculations or stepping) and dual-task (performing both single-tasks at once). Cognitive function was assessed in the older patients with the Trail-making test part B (TMT-B). Major outcomes were task performance, brain activation during task (oxygenated haemoglobin: Oxy-Hb) measured by NIRS, and TMT-B score. Mixed ANOVAs were used to compare task factors and age groups in task performance. Mixed ANOVAs also compared task factors, age group and time factors in task-induced changes in measured Oxy-Hb. Among the older participants, correlations between the TMT-B score and Oxy-Hb values measured in each single-task and in the dual-task were examined using a Pearson correlation coefficient. Oxy-Hb values were significantly increased in both the calculation task and the dual-task within patients in both age groups. However, the Oxy-Hb values associated with there were higher in the older group during the post-task period for the dual-task. Also, there were significant negative correlations between both task-performance accuracy and Oxy-Hb values during the dual-task and participant TMT-B scores.

Conclusions

Older adults demonstrated age-specific PFC activation in response to dual-task challenge. There was also a significant negative correlation between PFC activation during dual-task and executive/attentional function. These findings suggest that the high cognitive load induced by dual-task activity generates increased PFC activity in older adults. However, this relationship appeared to be strongest in participants with better baseline attention and executive functions.     

Halichonic acid,a new rearranged bisabolene-type sesquiterpene from a marine sponge Halichondria sp.

A new compound, halichonic acid (1), was isolated from a marine sponge Halichondria sp., together with (6R,7S)-7-amino-7,8-dihydro-α-bisabolene (2). The structure of 1 was elucidated by spectroscopic analysis and ECD spectrum calculation to be a rearranged bisabolene-type sesquiterpene having a 3-azabicyclo[3.3.1]nonene moiety. Compound 2 was cytotoxic against HeLa cells with an IC₅₀ value of 50?μM, whereas 1 did not show cytotoxicity even at 50?μM. It is possible that 1 is biosynthesized from farnesyl pyrophosphate and glycine, with rearrangement.     

Linear dichroism of Zn(II)-tetrapyridylporphine aggregates formed at the toluene/water interface

The apparent circular dichroism (CD) and the linear dichroism (LD) spectra of the aggregates of achiral zinc(II)-5,10,15,20-tetra(4-pyridyl)-21H,23H-porphine (ZnTPyP), formed at the toluene/water interface in a centrifugal liquid membrane (CLM) cell, were investigated by comparison with the microscopic CD and LD spectra of a single interfacial aggregate of ZnTPyP about 100 mum in length, measured by a microscope-spectropolarimeter. The interfacial ZnTPyP aggregate showed two types of flat trapezoidal shapes, one had a seedlike core at an edge (type I) and another a needlelike core at an edge (type II). The microscopic CD and LD spectra were observed by varying the angle between the parallel axis of the trapezoidal aggregate and the perpendicular axis of a polarized light for LD. The plot of the CD intensity against the LD intensity for a single aggregate, observed at a given wavelength, showed a rotated elliptical shape with a long axis through the origin, when the orientation angle was changed. From these results, it was concluded that the apparent CD spectra observed by the CLM-CD method were mainly due to the large linear dichroism of the aggregate. Both type I and type II structures showed two transition dipole moments, parallel and perpendicular to the long axis of the structure, but suggesting a more developed J-aggregate in type II structure. AFM measurements showed that the interfacial ZnTPyP aggregate had a multilayer structure, in which the unit monolayer thickness was 1.58 +/- 0.23 nm. Finally, the orientation angle of the interfacial aggregate in the CLM cell was estimated as 41 degrees -44 degrees to the rotating axis of the cell.