52 research outputs found
The aggregation of an alkyl-C<sub>60</sub> derivative as a function of concentration, temperature and solvent type
Contrast-variation SANS, SAXS, NMR and ITC measurements show that molecule1associates into micelles with tunable size based on the solution parameters.</p
Living Unimodal Growth of Polyion Complex Vesicles via Two-Dimensional Supramolecular Polymerization
Understanding the dynamic behavior of molecular self-assemblies
with higher-dimensional structures remains a key challenge to obtaining
well-controlled and monodispersed structures. Nonetheless, there exist
few systems capable of realizing the mechanism of supramolecular polymerization
at higher dimensions. Herein, we report the unique self-assembling
behavior of polyion complexes (PICs) consisting of poly(ethylene glycol)-polyelectrolyte
block copolymer as an example of two-dimensional supramolecular living
polymerization. Monodispersed and submicrometer unilamellar PIC vesicles
(nano-PICsomes) displayed time-dependent growth while maintaining
a narrow size distribution and a unilamellar structure. Detailed analysis
of the system revealed that vesicle growth proceeded through the consumption
of unit PICs (uPICs) composed of a single polycation/polyanion pair
and was able to restart upon the further addition of isolated uPICs.
Interestingly, the resulting vesicles underwent dissociation into
uPICs in response to mechanical stress. These results clearly frame
the growth as a two-dimensional supramolecular living polymerization
of uPICs
Fc-Binding Antibody-Recruiting Molecules for Cancer Therapy: Exploiting Endogenous IgG Without antigen–Fab Interactions
Small molecules emulating the effector functions of antibodies have potential clinical benefits because of their low immunogenicity. Antibody-recruiting molecules (ARMs) are bispecific molecules designed to redirect endogenous antibodies to targets. However, endogenous antibodies show intra/inter-patient differences regarding their concentrations and affinities, limiting the potential of ARMs. We sought to address this issue using a Fc-binding peptide instead of an antigen for antibody redirection. Fc-binding ARM (Fc-ARM) targeting folate receptor-α (FR-α) expressed on cancer cells, formed a ternary complex of Fc-ARM, FR-α, and antibody on cancer cells. The ability of this ternary complex to activate natural killer cells was positively correlated with its Fc affinity, and did not require the Fab region. Fc-ARM hitchhiked on pooled human IgG to enhance its blood retention, and suppressed tumor growth in a mouse xenograft model of human cancer. Thus, Fc-ARM has the potential to be employed as a less immunogenic alternative to therapeutic antibodies.</div
Ligand Design for Specific MHC Class I Molecules on the Cell Surface
We have validated
that ligand peptides designed from antigen peptides could be used for targeting
specific major histocompatibility complex class I (MHC-I) molecules on
cell surface. To design the ligand peptides, we used reported antigen peptides for
each MHC-I molecule with high binding affinity. From the crystal structure of
the peptide/MHC-I complexes, we determined a modifiable residue in the antigen
peptides and replaced this residue with a lysine with an ε-amine group modified with functional molecules. The
designed ligand peptides successfully bound to cells expressing the
corresponding MHC-I molecules via exchange of peptides bound to the MHC-I. We
demonstrated that the peptide ligands could be used to transport a protein or a
liposome to cells expressing the corresponding MHC-I. The present strategy may
be useful for targeted delivery to cells overexpressing MHC-I, which have been
observed autoimmune diseases.</p
Dietary Problems Are Associated with Frailty Status in Older People with Fewer Teeth in Japan
This study aimed to investigate the association between dietary problems and frailty according to tooth loss in older Japanese people. This cross-sectional study included 160 older people (mean age 82.6 years) from Japan. Frailty status was assessed using the Study of Osteoporotic Fractures (SOF) criteria, which consists of (i) weight loss > 5% in the past year, (ii) inability to perform five chair stands, and (iii) self-perceived reduced energy level. Frailty was defined as the presence of ≥2 items of SOF criteria. Multivariate logistic regression analyses were performed with frailty as the dependent variable and dietary problems as the independent variable, stratified according to having <20 teeth. Low appetite and no enjoyment of eating were associated with frailty after adjusting for covariates in participants with <20 teeth. Dietary problems, including low appetite, eating alone, and negative attitudes toward enjoyment of eating were associated with a self-perceived reduced energy level in participants with <20 teeth. However, this association was not observed in participants with ≥20 teeth. In older people with fewer teeth, dietary problems have been suggested to be associated with frailty. Therefore, it may be necessary to pay attention to dietary problems, especially in older people with tooth loss
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