Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis preceded by bronchial asthma or allergic sinusitis and accompanied by peripheral blood eosinophilia. Immunosuppressive drugs, such as cyclophosphamide in addition to high-dose glucocorticoids, are recommended for induction of remission in patients with severe EGPA. Although mepolizumab is widely recognized as remission induction therapy in non-fatal/non-organ disabling or relapsed/refractory EGPA, its efficacy and safety in induction of remission for severe cases have been ambiguous.
View Article and Find Full Text PDFMethods Mol Biol
November 2024
A 62-year-old man had bilateral eyelid swelling for 4 months. Two months before admission, he developed fatigue and lost 5 kg of bodyweight. Further examination revealed elevated serum C-reactive protein, normal angiotensin-converting enzyme, elevated proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA), and normal IgG4 concentration.
View Article and Find Full Text PDFAn efficient and versatile glycosylation methodology is crucial for the systematic synthesis of oligosaccharides and glycoconjugates. A direct intermolecular and an indirect intramolecular methodology have been developed, and the former can be applied to the synthesis of medium-to-long-chain glycans like that of nucleotides and peptides. The development of a generally applicable approach for the stereoselective construction of glycosidic bonds remains a major challenge, especially for the synthesis of 1,2- glycosides such as β-mannosides, β-L-rhamnosides, and β-D-arabinofuranosides with equatorial glycosidic bonds as well as α-D-glucosides with axial ones.
View Article and Find Full Text PDFCell surface glycans form various "glycan patterns" consisting of different types of glycan molecules, thus enabling strong and selective cell-to-cell recognition. We previously conjugated different N-glycans to human serum albumin to construct glycoalbumins mimicking natural glycan patterns that could selectively recognize target cells or control excretion pathways in mice. Here, we develop an innovative glycoalbumin capable of undergoing transformation and remodeling of its glycan pattern in vivo, which induces its translocation from the initial target to a second one.
View Article and Find Full Text PDFSince transition-metal-catalyzed reactions are one of the most powerful and direct approaches for the synthesis of organic molecules, translating them to biological systems for biomedical applications is an emerging field. The manipulation of transition metal reactions in biological settings for uncaging prodrugs and synthesizing bioactive drugs has been widely studied. To expand the toolbox of transition-metal-mediated prodrug strategy, this work introduces the 2'-alkynl-biphenylamine precursors for the synthesis of phenanthridine derivatives using a water-compatible gold-catalyzed hydroamination under mild conditions.
View Article and Find Full Text PDFThe capsular polysaccharide (CPS) is a major virulence factor of the pathogenic and a promising target for vaccine development. However, the synthesis of the 1,2--2-amino-2-deoxyglycoside core of CPS remains challenging to date. Here we develop a highly α-selective ZnI-mediated 1,2- 2-azido-2-deoxy chemical glycosylation strategy using 2-azido-2-deoxy glucosyl donors equipped with various 4,6--tethered groups.
View Article and Find Full Text PDFThe aims of this study were as follows: the (a) creation of a pregnant occupant finite element model based on pregnant uterine data from sonography, (b) development of the evaluation method for placental abruption using this model and (c) analysis of the effects of three factors (collision speed, seatbelt position and placental position) on the severity of placental abruption in simulations of vehicle collisions. The 30-week pregnant occupant model was developed with the uterine model including the placenta, uterine-placental interface, fetus, amniotic fluid and surrounding ligaments. A method for evaluating the severity of placental abruption on this pregnant model was established, and the effects of these factors on the severity of the injury were analyzed.
View Article and Find Full Text PDFMethods for producing drugs directly at the cancer site, particularly using bioorthogonal metal catalysts, are being explored to mitigate the side effects of therapy. Albumin-based artificial metalloenzymes (ArMs) catalyze reactions in living mice while protecting the catalyst in the hydrophobic pocket. Here, we describe the in situ preparation and application of biocompatible tumor-targeting ArMs using circulating albumin, which is abundant in the bloodstream.
View Article and Find Full Text PDFGenotyping-by-sequencing of 723 worldwide cucumber genetic resources revealed that cucumbers were dispersed eastward via at least three distinct routes, one to Southeast Asia and two from different directions to East Asia. The cucumber (Cucumis sativus) is an economically important vegetable crop cultivated and consumed worldwide. Despite its popularity, the manner in which cucumbers were dispersed from their origin in South Asia to the rest of the world, particularly to the east, remains a mystery due to the lack of written records.
View Article and Find Full Text PDFCells are covered with a thick layer of sugar molecules known as glycans. Abnormal glycosylation is a hallmark of cancer, and hypersialylation increases tumor metastasis by promoting immune evasion and inducing tumor cell invasion and migration. Inhibiting sialylation is thus a potential anticancer treatment strategy.
View Article and Find Full Text PDFβ-N-Acetylgalactosamine-containing glycans play essential roles in several biological processes, including cell adhesion, signal transduction, and immune responses. β-N-Acetylgalactosaminidases hydrolyze β-N-acetylgalactosamine linkages of various glycoconjugates. However, their biological significance remains ambiguous, primarily because only one type of enzyme, exo-β-N-acetylgalactosaminidases that specifically act on β-N-acetylgalactosamine residues, has been documented to date.
View Article and Find Full Text PDFRare sugars are known for their ability to suppress postprandial blood glucose levels. Therefore, oligosaccharides and disaccharides derived from rare sugars could potentially serve as functional sweeteners. A disaccharide [α-d-allopyranosyl-(1→2)-β-d-psicofuranoside] mimicking sucrose was synthesized from rare monosaccharides D-allose and D-psicose.
View Article and Find Full Text PDFCellulitis, abscess, or both are among the most common skin and soft tissue infections. Typically, cellulitis arises due to bacterial penetration through breaches in the skin's protective barrier. However, in cases of facial cellulitis, it is necessary to consider not only the breakdown of the skin barrier but also to differentiate odontogenic cellulitis.
View Article and Find Full Text PDFCompared with stereoselective glycosylation methods mainly addressed on the preparation of pyranose glycosides, the furanosylation has been more limited, especially for the 1,2- arabinofuranosylation. Herein, we report a novel stereoselective 1,2--arabinofuranosylation strategy using a conformationally restricted 3,5--xylylene-protected arabinofuranosyl donor on activation with B(CF) for desired targets in moderate to excellent yields and β-stereoselectivity. The effectiveness of the 1,2--arabinofuranosylation strategy was demonstrated successfully with various acceptors, including carbohydrate alcohols.
View Article and Find Full Text PDFThis study proposes a new method for radionuclide therapy that involves the use of oligomeric 2,6-diisopropylphenyl azides and a chelator to form stable complexes with metallic radionuclides. The technique works by taking advantage of the endogenous acrolein produced by cancer cells. The azides react with the acrolein to give a diazo derivative that immediately attaches to the nearest organelle, effectively anchoring the radionuclide within the tumor.
View Article and Find Full Text PDFL-Arabinofuranosides with β-linkages are present in several plant molecules, such as arabinogalactan proteins (AGPs), extensin, arabinan, and rhamnogalacturonan-II. We previously characterized a β-L-arabinofuranosidase from Bifidobacterium longum subsp. longum JCM 1217, Bll1HypBA1, which was found to belong to the glycoside hydrolase (GH) family 127.
View Article and Find Full Text PDFp16 overexpression is often used as a surrogate marker for human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma but remains an uncertain diagnostic tool for HPV-related sinonasal squamous cell carcinoma (SNSCC). Our study involved 79 consecutive SNSCC patients who were treated at a tertiary referral university hospital during 2006-2021. We retrospectively examined their clinical characteristics and conducted p16 immunohistochemistry and HPV detection.
View Article and Find Full Text PDFThe direct synthesis of drugs enables drugs to treat diseases without causing side effects in healthy tissues. Transition-metal reactions have been widely explored for uncaging and synthesizing bioactive drugs in biological environments because of their remarkable reactivity. Nonetheless, it is difficult to develop a promising method to achieve drug synthesis because blood cells and metabolites deactivate transition-metal catalysts.
View Article and Find Full Text PDFNumerous genetic resources of major crops have been introduced from around the world and deposited in Japanese National Agriculture and Food Research Organization (NARO) Genebank. Understanding their genetic variation and selecting a representative subset ("core collection") are essential for optimal management and efficient use of genetic resources. In this study, we conducted genotyping-by-sequencing (GBS) to characterize the genetic relationships and population structure in 755 accessions of melon genetic resources.
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