Publications by authors named "Eita Sasaki"

Targeted drug delivery in response to external stimuli is therapeutically desirable, but long-term drug retention at the target site after stimulation is turned off remains a challenge. Herein, we present a targeted-delivery strategy via irreversible aggregation of drug carriers in response to mild external heating. We constructed two types of polymeric micelles, DBCO-TRM and Az-TRM, having a thermo-responsive polymer shell based on N-isopropylacrylamide (NIPAAm) and incorporating alkyne and azide moieties, respectively.

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Although Green Fluorescent Protein (GFP) is useful and most widely used, steric hindrance due to its size and the time required for chromophore formation are complications. However, it is difficult to form chromophores with peptides to reduce the molecular weight. Therefore, we focused on peptides that can become fluorescent by binding to dyes.

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Article Synopsis
  • Twisted intramolecular charge transfer (TICT) occurs when certain fluorescent dyes, upon being excited by light, undergo charge transfer and rotation that typically leads to non-fluorescence.
  • Researchers found that modifying the size of substituents on rhodamine derivatives can adjust the strength of TICT and the resulting intramolecular steric repulsion.
  • They developed a fluorescence probe that leverages this concept to detect nitroreductase (NTR) activity, which initially shows little fluorescence but dramatically increases when the NTR enzyme reacts with the probe, confirming that the intended chemical reactions occur.
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Immunological imprinting by ancestral SARS-CoV-2 strains is thought to impede the robust induction of Omicron-specific humoral responses by Omicron-based booster vaccines. Here, we analyzed the specificity and neutralization activity of memory B (B) cells after repeated BA.5 exposure in individuals previously imprinted by ancestral strain-based mRNA vaccines.

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Fluorescence imaging is a powerful technique for visualizing biological events in living samples with high temporal and spatial resolution. Fluorescent probes emitting far-red to near infrared (NIR) fluorescence are particularly advantageous for imaging due to their high tissue permeability and low autofluorescence, as well as their suitability for multicolor imaging. Among the far-red to NIR fluorophores, Si-rhodamine is one of the most practical fluorophores for the development of tailor-made NIR fluorescent probes because of the relative ease of synthesis of various derivatives, the unique intramolecular spirocyclization behavior, and the relatively high water solubility and high photostability of the probes.

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Various control strategies are available for building fluorogenic probes to visualize biological events in terms of a fluorescence change. Here, we performed the time-dependent density functional theory (TD-DFT) computational analysis of the twisted intramolecular charge transfer (TICT) process in rhodamine dyes. On the basis of the results, we designed and synthesized a series of rhodamine dyes and established a fluorescence quenching strategy that we call steric repulsion-induced TICT (sr-TICT), in which the fluorescence quenching process is greatly accelerated by simple intramolecular twisting.

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D,L-Propargylglycine (PAG) has been widely used as a selective inhibitor to investigate the biological functions of cystathionine γ-lyase (CSE), which catalyzes the formation of reactive sulfur species (RSS). However, PAG also inhibits other PLP (pyridoxal-5'-phosphate)-dependent enzymes such as methionine γ-lyase (MGL) and L-alanine transaminase (ALT), so highly selective CSE inhibitors are still required. Here, we performed high-throughput screening (HTS) of a large chemical library and identified oxamic hydrazide 1 as a potent inhibitor of CSE (IC = 13 ± 1 μM (mean ± S.

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The stimulation of local immunity by vaccination is desirable for controlling virus replication in the respiratory tract. However, the local immune stimulatory effects of adjuvanted vaccines administered through the non-mucosal route are poorly understood. Here, we clarify the mechanisms by which non-mucosal inoculation of adjuvants stimulates the plasmacytoid dendritic cell (pDC)-dependent immunoglobulin (Ig)A response in the lungs.

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Article Synopsis
  • Aluminum salt adjuvants (Als) are commonly used in vaccines and can enhance immune response, but they may also cause chronic pain and other serious side effects in rare cases.
  • A study on guinea pigs showed varying degrees of muscle damage from different Al-containing vaccines, with the human papillomavirus vaccine causing the most severe inflammation and damage.
  • Despite this, the muscle injury observed was found to be repairable within a month, and the extent of damage seemed more related to the type of vaccine or aluminum salts used rather than the amount of aluminum.
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Fluorogenic probes for bioimaging have become essential tools for life science and medicine, and the key to their development is a precise understanding of the mechanisms available for fluorescence off/on control, such as photoinduced electron transfer (PeT) and Förster resonance energy transfer (FRET). Here we establish a new molecular design strategy to rationally develop activatable fluorescent probes, which exhibit a fluorescence off/on change in response to target biomolecules, by controlling the twisted intramolecular charge transfer (TICT) process. This approach was developed on the basis of a thorough investigation of the fluorescence quenching mechanism of -phenyl rhodamine dyes (commercially available as the QSY series) by means of time-dependent density functional theory (TD-DFT) calculations and photophysical evaluation of their derivatives.

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Monitoring the activities of proteases is an important requirement in biological and medical research. Near-infrared (NIR) fluorescent probes are particularly useful for fluorescence imaging, due to the high penetration of NIR and the low autofluorescence in tissue for this wavelength region, but most current NIR fluorescent probes for proteases are targeted to endopeptidase. Here, we describe a new molecular design for NIR fluorescent probes that target exopeptidase by utilizing the >110 nm blueshift of unsymmetrical Si-rhodamines upon amidation of the N atom of their xanthene moiety.

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Hydrogen sulfide and its oxidation products are involved in many biological processes, and sulfane sulfur compounds, which contain sulfur atoms bonded to other sulfur atom(s), as found in hydropersulfides (R-S-SH), polysulfides (R-S-S-S-R), hydrogen polysulfides (HS), etc., have attracted increasing interest. To characterize their physiological and pathophysiological roles, selective detection techniques are required.

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  • Alveolar macrophages play a crucial role in the immune response by releasing interleukin (IL)-1α when stimulated by fine particles, but the impact of isolation methods on their function is uncertain.
  • This study investigated how the volume of injection buffer used during bronchoalveolar lavage fluid (BALF) collection affects the viability and IL-1α release of primary mouse alveolar macrophages (mAM) in response to particle exposure.
  • Results showed that using a larger injection volume (1.0 ml) led to better cell viability and IL-1α release compared to smaller volumes (0.55 or 0.75 ml), indicating that the buffer volume can influence the functional responses of isolated macrophages.
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Aluminum hydroxide salts (alum) have been added to inactivated vaccines as safe and effective adjuvants to increase the effectiveness of vaccination. However, the exact cell types and immunological factors that initiate mucosal immune responses to alum adjuvants are unclear. In this study, the mechanism of action of alum adjuvant in nasal vaccination was investigated.

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Human T cell leukemia virus type 1 (HTLV-1) is mainly transmitted vertically through breast milk. The rate of mother-to-child transmission (MTCT) through formula feeding, although significantly lower than through breastfeeding, is approximately 2.4%-3.

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The efficacy of vaccine adjuvants depends on their ability to appropriately enhance the immunogenicity of vaccine antigens, which is often insufficient in non-adjuvanted vaccines. Genomic analyses of immune responses elicited by vaccine adjuvants provide information that is critical for the rational design of adjuvant vaccination strategies. In this study, biomarker genes from the genomic analyses of lungs after priming were used to predict the efficacy and toxicity of vaccine adjuvants.

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Article Synopsis
  • The structure of lincomycin A features a unique eight-carbon thiosugar core called methyllincosamide (MTL), with an added -methylprolinyl group.
  • Previous research indicated GDP-ᴅ-α-ᴅ-octose and GDP-ᴅ-α-ᴅ-lincosamide as key intermediates in the MTL biosynthesis pathway, but the specific enzyme reactions for converting GDP-ᴅ-α-ᴅ-octose to GDP-ᴅ-α-ᴅ-lincosamide were unclear until now.
  • This study describes a new biosynthetic subpathway with four enzymes (LmbM, LmbL, CcbZ, C
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Introduction: A novel adjuvant evaluation system for safety and immunogenicity is needed. Vaccination is important for infection prevention, for example, from influenza viruses. Adjuvants are considered critical for improving the effectiveness of influenza vaccines.

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The safety evaluation of vaccines is critical to avoid the development of side effects in humans. To increase the sensitivity of detection for toxicity tests, it is important to capture not only pathological changes but also physiological changes. H nuclear magnetic resonance (NMR) spectroscopy analysis of biofluids produces profiles that show characteristic responses to changes in physiological status.

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The enzyme lumazine synthase (LS) has been engineered to self-assemble into hollow-shell structures that encapsulate unnatural cargo proteins through complementary electrostatic interactions. Herein, we show that a negatively supercharged LS variant can also form organic-inorganic hybrids with gold nanomaterials. Simple mixing of LS pentamers with positively charged gold nanocrystals in aqueous buffer spontaneously affords protein-shelled gold cores.

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Proteins are excellent materials for constructing nano- to micro-meter sized compartments. For example, in nature, hollow spherical shells made of proteins, called protein cages, are widespread. Prominent examples include viruses, ferritins, carboxysomes, and others.

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Vaccines effectively prevent infectious diseases. Many types of vaccines against various pathogens that threaten humans are currently in widespread use. Recently, adjuvant adaptation has been attempted to activate innate immunity to enhance the effectiveness of vaccines.

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Article Synopsis
  • Influenza is a yearly epidemic, and maintaining the safety and potency of vaccines through quality control is crucial for public trust.
  • Clinical trials and animal safety tests help ensure these vaccines are consistent and safe by evaluating biological responses such as body weight and white blood cell count.
  • Recent advancements in cDNA microarray technology have identified 17 marker genes that correlate with biological changes in vaccinated animals, potentially providing a new method for rapid safety assessment of influenza vaccines.
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Recently, many vaccine adjuvants have been developed; however, most of the newly developed adjuvants have been dropped out of preclinical and clinical trials owing to their unexpected toxicity. Thus, the development of highly quantitative and comparable screening methods for evaluating adjuvant safety is needed. In a previous study, we identified specific biomarkers for evaluating the safety of an intranasal influenza vaccine with CpG K3 adjuvant by comparing biomarker expression.

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Article Synopsis
  • - The study focuses on the importance of safety evaluations for human vaccines to prevent unexpected adverse reactions, highlighting a lack of preclinical systems to assess these reactions.
  • - Researchers aimed to create a novel humanized mouse model that preserves human immune cells to test the safety of influenza vaccines by using previously identified biomarker genes for evaluation.
  • - Results show that a short-term humanized mouse model retained specific human immune cells and demonstrated a more pronounced response to a toxic reference vaccine compared to a long-term model, making it a better tool for vaccine safety assessments.
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