Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy accompanied by impaired differentiation and autonomous proliferation of hematopoietic stem cells. Standard induction therapy ...results in first complete remission among 70% of patients with AML; however, approximately half of these patients relapse and become refractory. Allogeneic hematopoietic cell transplantation is a useful treatment for relapsed and refractory cases. However, transplantation-related mortality is approximately 20%, which is not a low value, and quality of life after transplantation decreases. Therefore, there is a need to stratify the prognosis of each patient and implement this treatment appropriately. Owing to recent advances in genome analysis technology, many gene mutations involved in onset and recurrence of AML have been discovered. These abnormalities and mutations not only have clinical application as prognostic factors and minimal residual disease markers, but they may also contribute to novel molecular targeted drug development. Many new drugs such as first-generation FMS-like tyrosine kinase 3 (FLT3), isocitrate dehydrogenase 1 and 2 (IDH1/2), and B cell lymphoma 2 (BCL2) inhibitors have been developed in the West. In addition, the second-generation FLT3 inhibitors gilteritinib and quizartinib were developed in Japan, and treatment outcomes for patients with AML have improved. However, there is still a large disparity in drug availability between the West, and Japan. As a result, treatment guidelines in the West cannot be applied in the clinical setting in Japan. In this study, we assessed the molecular target drug treatment by gene diagnosis for treatment of AML patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Our understanding of allergic contact dermatitis mechanisms has progressed over the past decade. Innate immune cells that are involved in the pathogenesis of allergic contact dermatitis include ...Langerhans cells, dermal dendritic cells, macrophages, mast cells, innate lymphoid cells (ILCs), neutrophils, eosinophils, and basophils. ILCs can be subcategorized as group 1 (natural killer cells; ILC1) in association with Th1, group 2 (ILC2) in association with Th2, and group 3 (lymphoid tissue-inducer cells; ILC3) in association with Th17. Pattern recognition receptors (PRRs) including toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) in innate immune cells recognize damage-associated molecular patterns (DAMPs) and cascade the signal to produce several cytokines and chemokines including tumor necrosis factor (TNF)-α, interferon (IFN)-α, IFN-γ, interleukin (IL)-1β, IL-4, IL-6, IL-12, IL-13, IL-17, IL-18, and IL-23. Here we discuss the recent findings showing the roles of the innate immune system in allergic contact dermatitis during the sensitization and elicitation phases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment loss, respectively. In AA, ...inflammatory cell infiltrates are in the deep reticular dermis close to the hair bulb (swarm of bees), whereas in vitiligo the inflammatory infiltrates are in the epidermis and papillary dermis. Immune privilege collapse has been extensively investigated in AA pathogenesis, including the suppression of immunomodulatory factors (e.g., transforming growth factor-β (TGF-β), programmed death-ligand 1 (PDL1), interleukin-10 (IL-10), α-melanocyte-stimulating hormone (α-MSH), and macrophage migration inhibitory factor (MIF)) and enhanced expression of the major histocompatibility complex (MHC) throughout hair follicles. However, immune privilege collapse in vitiligo remains less explored. Both AA and vitiligo are autoimmune diseases that share commonalities in pathogenesis, including the involvement of plasmacytoid dendritic cells (and interferon-α (IFN- α) signaling pathways) and cytotoxic CD8+ T lymphocytes (and activated IFN-γ signaling pathways). Blood chemokine C-X-C motif ligand 9 (CXCL9) and CXCL10 are elevated in both diseases. Common factors that contribute to AA and vitiligo include oxidative stress, autophagy, type 2 cytokines, and the Wnt/β-catenin pathway (e.g., dickkopf 1 (DKK1)). Here, we summarize the commonalities and differences between AA and vitiligo, focusing on their pathogenesis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This paper demonstrates how the shape and size of gold nanoparticles (AuNPs) affect immunological responses in vivo and in vitro for the production of antibodies for West Nile virus (WNV). We ...prepared spherical (20 and 40 nm in diameter), rod (40 × 10 nm), and cubic (40 × 40 × 40 nm) AuNPs as adjuvants and coated them with WNV envelope (E) protein. We measured anti-WNVE antibodies after inoculation of these WNVE-coated AuNPs (AuNP-Es) into mice. The 40 nm spherical AuNP-Es (Sphere40-Es) induced the highest level of WNVE-specific antibodies, while rod AuNP-Es (Rod-Es) induced only 50% of that of Sphere40-E. To examine the mechanisms of the shape-dependent WNVE antibody production, we next measured the efficiency of cellular uptake of AuNP-Es into RAW264.7 macrophage cells and bone-marrow-derived dendritic cells (BMDCs) and the subsequent cytokine secretion from BMDCs. The uptake of Rod-Es into the cells proceeded more efficiently than those of Sphere-Es or cubic WNVE-coated AuNPs (Cube-Es), suggesting that antibody production was not dependent on the uptake efficiency of the different AuNP-Es. Cytokine production from BMDCs treated with the AuNP-Es revealed that only Rod-E-treated cells produced significant levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18), indicating that Rod-Es activated inflammasome-dependent cytokine secretion. Meanwhile, Sphere40-Es and Cube-Es both significantly induced inflammatory cytokine production, including tumor necrosis factor-α (TNF-α), IL-6, IL-12, and granulocyte macrophage colony-stimulating factor (GM-CSF). These results suggested that AuNPs are effective vaccine adjuvants and enhance the immune response via different cytokine pathways depending on their sizes and shapes.
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IJS, KILJ, NUK, PNG, UL, UM
Yezo virus is a novel virus transmitted by tick bites that causes fever with thrombocytopenia. To date, two reports have been published on patients with Yezo virus infection. However, the clinical ...characteristics of Yezo virus infection remain unclear. A patient who presented with fever, fatigue, headaches, and muscle pain and was admitted to our hospital. The patient had thrombocytopenia, leukopenia, and elevated liver enzyme and serum ferritin levels. The patient was diagnosed with Yezo virus and Borrelia miyamotoi coinfection based on the detection of Yezo virus in a blood sample by PCR and the detection of elevated serum antibody titers to Yezo virus and Borrelia miyamotoi.
The curing process of poly(dimethylsiloxane) (PDMS) was microscopically investigated by the single-molecule tracking method based on the diffusion motion of fluorescent dye molecules adding to the ...PDMS layer stored at a temperature of 308K. The PDMS layer was completely cured at 900 min after adding a curing agent. We compared the time- and ensemble-averaged mean square displacements (MSDs) of the tracked molecules at 90, 510, and 900 min after adding the curing agent into the PDMS layer. The discrepancies were observed between the time- and ensemble-averaged MSDs, indicating weak ergodicity breaking. The spatially averaged diffusion coefficient exhibited a two-step decrease: first step was rapid decrease suggesting the extent of crosslinking, and second step was slow one suggesting the increase of crosslink density. The single-molecule trajectory scale analysis revealed the heterogeneous distribution of the diffusion coefficient. By calculating the heat map from the slope of moment scaling spectrum (MSS) of each single-molecule trajectory, cluster structures were recognized. The spatial correlation of the slope of MSS decreased with the time elapsed. These results suggested the existence of the heterogeneous structure in the PDMS layer during the curing process.
•The curing process of poly(dimethylsiloxene) (PDMS) was microscopically investigated by the single-molecule tracking (SMT) method.•The weak ergodicity breaking was observed.•Both normal and confined diffusions were observed in the PDMS layer during the curing process.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Total reflection X‐ray fluorescence (TXRF) is widely used for trace elemental analysis, wherein a thin monochromatic X‐ray beam is typically applied at glancing angles. The actual volume of ...the sample measured by the instrument (analysis volume) depends on the dimensions of the X‐ray beam and glancing angle, and it is a key feature in sample preparation for TXRF analysis. Herein, the analysis volume, including the analysis region and analysis height, was experimentally evaluated. A thin Au layer approximately 5 nm thick and 1 mm in diameter was prepared at a specific position on a flat glass substrate using a vacuum evaporation device. The position of this Au layer was controlled by manipulating a mask plate with a small hole. Nine samples were prepared at different Au layer positions and analyzed at 8 azimuth angles using a tabletop TXRF instrument. Finally, the Au XRF intensity distribution was visualized on a glass substrate. It was found that the XRF emitted over a diameter of approximately 5 mm was effectively detected using the tabletop TXRF instrument. The analysis height was experimentally evaluated using a thin Au layer deposited on a polyimide film 5 mm in diameter and 5 nm thick. The Au layer height was adjusted by inserting polyimide thin films between the Au layer and the glass substrate. The Au XRF intensity drastically decreased with increasing Au layer height, suggesting that the XRF emitted from the sample is effectively detected at heights of <10 μm by using the described setup.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Caenorhabditis elegans contains two pathways for propionate metabolism, the vitamin B12-dependent and shunt pathways, which are similar to those in humans. In this study, we monitored the changes in ...propionate metabolism in the whole body of C. elegans using novel 13CO2 gas analysis. We measured the increase in 13CO2 excreted in the air after administering 1-13C-labeled propionate (13Cpropionate) to the worms. The 13CO2 generated from 13Cpropionate in C. elegans increased in a dose-dependent manner, reaching a maximum at 48 h. Enhanced expression of propionate metabolism-related genes was observed after administration of propionate. Knockdown of mmcm-1, which encodes the rate-limiting enzyme of the propionate metabolism, using RNAi reduced 13CO2 excretion. Thus, 13CO2 gas analysis could be confirmed 13CO2 excretion associated with changes in the metabolism of 13Cpropionate in nematodes. This analysis can contribute to further understanding of the physiological effects of short-chain fatty acids.
A variety of insect species induce galls on host plants. Several studies have implicated phytohormones in insect-induced gall formation. However, it has not been determined whether insects can ...synthesize phytohormones. It has also never been established that phytohormones function in gall tissues.
Liquid chromatography and tandem mass spectrometry (LC/MS/MS) were used to analyse concentrations of endogenous cytokinins and the active auxin IAA in the gall-inducing sawfly (Pontania sp.) and its host plant, Salix japonica. Feeding experiments demonstrated the ability of sawfly larvae to synthesize IAA from tryptophan. Gene expression analysis was used to characterize hormonal signalling in galls.
Sawfly larvae contain high concentrations of IAA and t-zeatin, and produce IAA from tryptophan. The glands of adult sawflies, the contents of which are injected into leaves upon oviposition and are involved in the initial stages of gall formation, contain an extraordinarily high concentration of t-zeatin riboside. Transcript levels of some auxin-and cytokinin-responsive genes are significantly higher in gall tissue than in leaves.
The abnormally high concentration of t-zeatin riboside in the glands strongly suggests that the sawfly can synthesize cytokinins as well as IAA. Gene expression profiles indicate high levels of auxin and cytokinin activities in growing galls.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
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