Emerging Immunotherapy for Acute Myeloid Leukemia

Several immune checkpoint molecules and immune targets in leukemic cells have been investigated. Recent studies have suggested the potential clinical benefits of immuno-oncology (IO) therapy against acute myeloid leukemia (AML), especially targeting CD33, CD123, and CLL-1, as well as immune checkpoint inhibitors (e.g., anti-PD (programmed cell death)-1 and anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) antibodies) with or without conventional chemotherapy. Early-phase clinical trials of chimeric antigen receptor (CAR)-T or natural killer (NK) cells for relapsed/refractory AML showed complete remission (CR) or marked reduction of marrow blasts in a few enrolled patients. Bi-/tri-specific antibodies (e.g., bispecific T-cell engager (BiTE) and dual-affinity retargeting (DART)) exhibited 11–67% CR rates with 13–78% risk of cytokine-releasing syndrome (CRS). Conventional chemotherapy in combination with anti-PD-1/anti-CTLA4 antibody for relapsed/refractory AML showed 10–36% CR rates with 7–24 month-long median survival. The current advantages of IO therapy in the field of AML are summarized herein. However, although cancer vaccination should be included in the concept of IO therapy, it is not mentioned in this review because of the paucity of relevant evidence.     

Biomarkers for colorectal cancer

Colorectal cancer (CRC) is the third most common epithelial malignancy in the world. Since CRC develops slowly from removable precancerous lesions, detection of the lesion at an early stage by regular health examinations can reduce the incidence and mortality of this malignancy. Colonoscopy significantly improves the detection rate of CRC, but the examination is expensive and inconvenient. Therefore, we need novel biomarkers that are non-invasive to enable us to detect CRC quite early. A number of validation studies have been conducted to evaluate genetic, epigenetic or protein markers for identification in the stool and/or serum. Currently, the fecal occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics will lead to the discovery of novel non-invasive biomarkers.     

Control of optical bandgap energy and optical absorption coefficient by geometric parameters in sub-10 nm silicon-nanodisc array structure

A sub-10 nm, high-density, periodic silicon-nanodisc (Si-ND) array has been fabricated using a new top-down process, which involves a 2D array bio-template etching mask made of Listeria-Dps with a 4.5 nm diameter iron oxide core and damage-free neutral-beam etching (Si-ND diameter: 6.4 nm). An Si-ND array with an SiO(2) matrix demonstrated more controllable optical bandgap energy due to the fine tunability of the Si-ND thickness and diameter. Unlike the case of shrinking Si-ND thickness, the case of shrinking Si-ND diameter simultaneously increased the optical absorption coefficient and the optical bandgap energy. The optical absorption coefficient became higher due to the decrease in the center-to-center distance of NDs to enhance wavefunction coupling. This means that our 6 nm diameter Si-ND structure can satisfy the strict requirements of optical bandgap energy control and high absorption coefficient for achieving realistic Si quantum dot solar cells.     

Cancer chemopreventive ability of conjugated linolenic acids

Conjugated fatty acids (CFA) have received increased interest because of their beneficial effects on human health, including preventing cancer development. Conjugated linoleic acids (CLA) are such CFA, and have been reviewed extensively for their multiple biological activities. In contrast to other types of CFAs including CLA that are found at low concentrations (less than 1%) in natural products, conjugated linolenic acids (CLN) are the only CFAs that occur in higher quantities in natural products. Some plant seeds contain a considerably high concentration of CLN (30 to 70 wt% lipid). Our research group has screened CLN from different plant seed oils to determine their cancer chemopreventive ability. This review describes the physiological functions of CLN isomers that occur in certain plant seeds. CLN are able to induce apoptosis through decrease of Bcl-2 protein in certain human cancer cell lines, increase expression of peroxisome proliferator-activated receptor (PPAR)-γ, and up-regulate gene expression of p53. Findings in our preclinical animal studies have indicated that feeding with CLN resulted in inhibition of colorectal tumorigenesis through modulation of apoptosis and expression of PPARγ and p53. In this review, we summarize chemopreventive efficacy of CLN against cancer development, especially colorectal cancer.     

Preparation and characterization of multilayered hydroxyapatite/silk fibroin film

We prepared multilayered films consisting of silk fibroin (SF) and hydroxyapatite (HAp) by alternating lamination using untreated SF and HAp-deposited SF films. Untreated SF films were prepared from a regenerated SF solution by air drying. HAp-deposited SF films were prepared by soaking methanol-treated SF films containing >5 wt% CaCl2 in a simulated body fluid with the ion concentration 1.5-fold higher than that of the standard one. The multilayered HAp/SF films had HAp layers with approximate thicknesses of 3-5 microm and SF layers with thicknesses of 40-70 microm. The bonding strength between the SF and HAp layers was significantly affected by temperature and compression time under the lamination method. The optimal conditions for achieving the maximum T-peel strength and beta-sheet contents were determined to be 130 degrees C for 4 min. The Young's modulus of the multilayered films (133.4 MPa) was higher than that of the films consisting of SF alone (92.5 MPa) under swollen conditions. The biocompatibility of the HAp-deposited SF films was analyzed by culturing of osteoblasts (MC3T3-E1) on a film. The results indicate that HAp-deposited SF films and SF films show similar degrees of cell adhesion and alkaline phosphatase activities.     

Polymer film produced by a marine bacterium

Biojelly is a sort of polymer that is formed on a cellulose acetate membrane immersed in seawater. Interestingly, Biojelly inhibits attachment of marine organisms such as algae and barnacles. We could successfully isolate several marine microorganisms from Biojelly-attached microorganisms. One of these isolates, strain SHY1-1, produced water-insoluble polymeric materials in natural seawater supplemented with yeast extracts and glucose. This strain was assigned to be Alteromonas sp. by the method of the 165 rRNA gene sequencing and phylogenetic analysis. Biojelly and the polymer film produced by Alteromonas sp. SHY1-1 were qualitatively characterized by Fourier transformed infrared (FT-IR) spectroscopy and thin-layer chromatography (TLC). The result indicated that naturally occurring Biojelly and the polymeric materials obtained in this work both were a sort of mucopolysaccharide consisting of amino sugars. In addition, the attachment assay with larvae indicated that both polymer films had similar anti-fouling activity against barnacle (Balanus amphitrite).     

Deposition of bone‐like apatite on modified silk fibroin films from simulated body fluid

Silk fibroin films with various calcium chloride contents were prepared by a cast film method and subsequent MeOH treatment. The conformational changes from α‐helix to β‐sheet structure were analyzed by Fourier transformed infrared attenuated total reflection spectroscopy measurements. The films obtained were soaked in 1.5‐times simulated body fluid (1.5 SBF) and the deposition of hydroxyapatite crystals were observed by scanning electron microscopy. The films with calcium chloride contents lower than 3 wt % relative to the silk fibroin were not mineralized under these conditions, while those with calcium chloride contents more than 5 wt % mineralized after 6 h. The X‐ray diffraction patterns and inductive coupled plasma spectroscopy analyses indicated that the hydroxyapatite crystals were grown by hydrolysis of octacalcium phosphate, as indicated by differences in diffraction intensities and changes in concentrations of calcium and phosphate ions in 1.5 SBF. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006     

Synthesis and Self-Assembly Properties of Bola-Amphiphilic Glycosylated Lipopeptide-Type Supramolecular Hydrogels Showing Colour Changes Along with Gel–Sol Transition

Supramolecular hydrogels formed by self-assembly of low-molecular-weight amphiphiles (hydrogelators) have attracted significant attention, as smart and soft materials. However, most of the observed stimuli-responsive behaviour of these supramolecular hydrogels are limited to gel–sol transitions. In this study, we present bola-amphiphilic glycosylated lipopeptide-type supramolecular hydrogelators that exhibit reversible thermochromism along with a gel–sol transition. The bola-amphiphiles have mono-, di-, tri- or tetra-phenylalanine (F) as a short peptide moiety. We investigate and discuss the effects of the number of F residues on the gelation ability and the morphology of the self-assembled nanostructures.     

Development of a Novel Time-Temperature Integrator/Indicator (TTI) Based on the Maillard Reaction for Visual Thermal Monitoring of the Cooking Process

There is a lack of easy-to-use hardware providing clear indications regarding both current temperature and temperature history during thermal processing. The objective of this study was to use the Maillard reaction to develop a novel time-temperature integrator/indicator (TTI) that would be able to perform these tasks during the cooking process. To this end, we comprehensively tested the Maillard reaction using various conditions to determine those under which the reaction illustrated obvious color change when temperature was held at 75 °C for 1 min, which is the recommendation of the Japanese government regarding safe meat product cooking. After adjusting various parameters related to the reaction, we managed to deduce a reaction system of d-ribose (7.0 mol/kg) and l-lysine (3.0 mol/kg) with dibasic potassium phosphate (0.5 mol/kg) satisfying the color-change criterion. The developed Maillard reaction-based TTI consisted of two transparent plastic poaches connected through a loose half-seal. Breaking the half-seal by pushing with fingers results in the mixing of the solutions and the initiation of the Maillard reaction. The TTI was tested in hamburger cooking and its color clearly changed from colorless to brown in hamburger during the 1-min hold at 75 °C, and also successfully eliminated viable 10⁶ CFU/g Escherichia coli O157:H7 cells. The developed TTI will enable to help ensure microbiological safety.