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1.
J Exp Clin Cancer Res ; 42(1): 272, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37858248

RESUMO

BACKGROUND: Immunotherapy has significantly advanced cancer treatments, but many patients do not respond to it, partly due to immunosuppressive mechanisms used by tumor cells. These cells employ immunosuppressive ligands to evade detection and elimination by the immune system. Therefore, the discovery and characterization of novel immunosuppressive ligands that facilitate immune evasion are crucial for developing more potent anti-cancer therapies. METHODS: We conducted gain-of-function screens using a CRISPRa (CRISPR activation) library that covered the entire human transmembrane sub-genome to identify surface molecules capable of hindering NK-mediated cytotoxicity. The immunosuppressive role and mechanism of MUC21 were validated using NK and T cell mediated cytotoxicity assays. Bioinformatics tools were employed to assess the clinical implications of mucin-21 (MUC21) in cancer cell immunity. RESULTS: Our genetic screens revealed that MUC21 expression on cancer cell surfaces inhibits both the cytotoxic activity of NK cells and antibody-dependent cellular cytotoxicity, but not affecting complement-dependent cytotoxicity. Additionally, MUC21 expression hinders T cell activation by impeding antigen recognition, thereby diminishing the effectiveness of the immune checkpoint inhibitor, anti-PD-L1. Moreover, MUC21 expression suppress the antitumor function of both CAR-T cells and CAR-NK cells. Mechanistically, MUC21 facilitates immune evasion by creating steric hindrance, preventing interactions between cancer and immune cells. Bioinformatics analysis revealed elevated MUC21 expression in lung cancer, which correlated with reduced infiltration and activation of cytotoxic immune cells. Intriguingly, MUC21 expression was higher in non-small cell lung cancer (NSCLC) tumors that were non-responsive to anti-PD-(L)1 treatment compared to responsive tumors. CONCLUSIONS: These findings indicate that surface MUC21 serves as a potent immunosuppressive ligand, shielding cancer cells from NK and CD8+T cell attacks. This suggests that inhibiting MUC21 could be a promising strategy to improve cancer immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Imunidade Celular , Células Matadoras Naturais , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo
2.
Environ Res ; 228: 115873, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37062482

RESUMO

Nitrate sources in surface water have been identified using dual-isotope compositions of nitrate with various tools to efficiently manage the water quality at the local scale. Correlation between Cl and NO3 has also been used to identify NO3. In this study, we assess the reliability of the dual-isotope approach and Cl in terms of nitrate source apportionment. To this end, we collected stream water samples throughout South Korea to estimate nitrate sources in streams and determine whether the land-use pattern was closely related to nitrate sources. The δ15N-NO3 ranging from -1.3 to 14.8‰ showed a spatial distribution that was lower in mountain ranges (<7‰) than plain areas (>8‰). The Cl concentration in this national-scale distribution was also assessed. The relationship between the proportion of Cl and δ15N-NO3 classifies nitrate sources into areas characterized by three land-use patterns: (1) agricultural and business areas, (2) forests in highlands, and (3) lowland forests, of which (1) had proportions of Cl >50%, while (2) and (3) were <50%. The samples in (3) showed δ15N-NO3 values > 6‰, similar to those of (1). Deuterium excess of samples was negatively correlated (R2 = 0.53) with δ15N-NO3, accounting for the fact that δ15N-NO3 reflected land-use patterns. Samples were dominantly affected by agriculture-derived sources and domestic sewage showed NO3/Cl of <0.4 and δ15N-NO3 of >6‰. These results suggest that nitrate source apportionment should be comprehensively evaluated considering the dual-isotope approach, land-use patterns, and Cl proportions.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Nitratos/análise , Rios , Isótopos de Nitrogênio/análise , Cloretos , Poluentes Químicos da Água/análise , Reprodutibilidade dos Testes , Monitoramento Ambiental/métodos , China
3.
Sci Total Environ ; 880: 163353, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37023824

RESUMO

Both the smelter and acid mine drainage (AMD) in uppermost streams impact water geochemistry and deteriorate water quality. Efficient water quality management requires identifying the contribution of each source to stream water geochemistry. In this study, we aimed to determine the natural and anthropogenic sources (AMD and smelting) affecting water geochemistry by considering seasonality. Water samples were collected, from May 2020 to April 2021, in a main channel (Nakdong River) and tributaries in a small watershed including mines and smelters. The watershed is characterized by a carbonate-rich area in the upper-middle reaches and silicate-rich area in the middle-lower reaches. On the plots of Ca/Na vs. Mg/Na and 2(Ca + Mg) vs. HCO3 + 2SO4, the water geochemistry was predominantly explained by the carbonate and silicate weathering associated with sulfuric and carbonic acids. According to typical δ15N values for sources, nitrate contribution from soil-N mainly impacted water geochemistry, regardless of seasonality; the contribution from agricultural activity and sewage was negligible. Water geochemistry in the main channel samples was discriminated before and after passing through the smelter. The effects of the smelter were evident in elevated SO4, Zn, and Tl concentrations and in δ66Zn values; this was further supported by the relationships between Cl/HCO3 and SO4/HCO3 and between δ66Zn and Zn. These results were pronounced during winter, when the flush-out effect was absent. Our results suggest that multi-isotopes and chemical composition analyses can trace multiple sources influencing the water geochemistry in watersheds containing AMD and smelters.

4.
Blood ; 141(18): 2224-2238, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-36724450

RESUMO

The gut microbiome influences cancer development and the efficacy and safety of chemotherapy but little is known about its effects on lymphoma. We obtained stool samples from treatment-naive, newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) (n = 189). We first performed 16S ribosomal RNA gene sequencing (n = 158) and then conducted whole-genome shotgun sequencing on additional samples (n = 106). We compared the microbiome data from these patients with data from healthy controls and assessed whether microbiome characteristics were associated with treatment outcomes. The alpha diversity was significantly lower in patients with DLBCL than in healthy controls (P < .001), and the microbial composition differed significantly between the groups (P < .001). The abundance of the Enterobacteriaceae family belonging to the Proteobacteria phylum was markedly higher in patients than in healthy controls. Functional analysis of the microbiome revealed an association with opportunistic pathogenesis through type 1 pili, biofilm formation, and antibiotics resistance. Enterobacteriaceae members were significantly enriched in patients who experienced febrile neutropenia and in those who experienced relapse or progression (P < .001). Interestingly, greater abundance of Enterobacteriaceae correlated with shorter progression-free survival (P = .007). The cytokine profiles of patients whose microbiome was enriched with Enterobacteriaceae were significantly associated with interleukin 6 (P = .035) and interferon gamma (P = .045) levels. In summary, patients with DLBCL exhibited gut microbial dysbiosis. The abundance of Enterobacteriaceae correlated with treatment outcomes and febrile neutropenia. Further study is required to elucidate the origin and role of gut dysbiosis in DLBCL.


Assuntos
Neutropenia Febril , Microbioma Gastrointestinal , Linfoma Difuso de Grandes Células B , Humanos , Disbiose/complicações , Recidiva Local de Neoplasia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/complicações , RNA Ribossômico 16S/análise , RNA Ribossômico 16S/genética , Fezes/microbiologia
5.
Bioeng Transl Med ; 8(1): e10362, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36684086

RESUMO

Adoptive cell therapy (ACT) with antigen-specific T cells is a promising treatment approach for solid cancers. Interleukin-2 (IL-2) has been utilized in boosting the efficacy of ACT. However, the clinical applications of IL-2 in combination with ACT is greatly limited by short exposure and high toxicities. Herein, a complex coacervate was designed to intratumorally deliver IL-2 in a sustained manner and protect against proteolysis. The complex coacervate consisted of fucoidan, a specific IL-2 binding glycosaminoglycan, and poly-l-lysine, a cationic counterpart (FPC2). IL-2-laden FPC2 exhibited a preferential bioactivity in ex vivo expansion of CD8+T cells over Treg cells. Additionally, FPC2 was embedded in pH modulating injectable gel (FPC2-IG) to endure the acidic tumor microenvironment. A single intratumoral administration of FPC2-IG-IL-2 increased expansion of tumor-infiltrating cytotoxic lymphocytes and reduced frequencies of myeloid populations. Notably, the activation and persistency of tumor-reactive T cells were observed only in the tumor site, not in the spleen, confirming a localized effect of FPC2-IG-IL-2. The immune-favorable tumor microenvironment induced by FPC2-IG-IL-2 enabled adoptively transferred TCR-engineered T cells to effectively eradicate tumors. FPC2-IG delivery system is a promising strategy for T-cell-based immunotherapies.

6.
Front Plant Sci ; 14: 1337926, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38264017

RESUMO

The demand for high-quality strawberries continues to grow, emphasizing the need for innovative agricultural practices to enhance both yield and fruit quality. In this context, the utilization of natural products, such as biostimulants, has emerged as a promising avenue for improving strawberry production while aligning with sustainable and eco-friendly agricultural approaches. This study explores the influence of a bacterial filtrate (BF), a vegetal-derived protein hydrolysate (PH), and a standard synthetic auxin (SA) on strawberry, investigating their effects on yield, fruit quality, mineral composition and metabolomics of leaves and fruits. Agronomic trial revealed that SA and BF significantly enhanced early fruit yield due to their positive influence on flowering and fruit set, while PH treatment favored a gradual and prolonged fruit set, associated with an increased shoot biomass and sustained production. Fruit quality analysis showed that PH-treated fruits exhibited an increase of firmness and soluble solids content, whereas SA-treated fruits displayed lower firmness and soluble solids content. The ionomic analysis of leaves and fruits indicated that all treatments provided sufficient nutrients, with heavy metals within regulatory limits. Metabolomics indicated that PH stimulated primary metabolites, while SA and BF directly affected flavonoid and anthocyanin biosynthesis, and PH increased fruit quality through enhanced production of beneficial metabolites. This research offers valuable insights for optimizing strawberry production and fruit quality by harnessing the potential of natural biostimulants as viable alternative to synthetic compounds.

7.
Food Sci Biotechnol ; 31(5): 561-570, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35529684

RESUMO

The effects of concentration, temperature, and time on infusion of fluorescein into corn and waxy rice starches and their controlled release pattern were investigated. At low fluorescein concentration (1 µM), temperature significantly affected infusion efficiency. At high fluorescein concentration (50-150 µM), temperature showed little effect; fluorescein concentration significantly affected infusion efficiency. Corn starch showed relatively higher infusion efficiency than waxy rice starch at high concentration. During controlled release, 50% and 81% of infused fluorescein were released from corn and waxy rice starches, respectively, after bacterial α-amylase treatment. However, 61% and 68% of infused fluorescein were released from corn and waxy rice starches, respectively, after pancreatic α-amylase treatment. The dextrose equivalent (DE) value revealed similar patterns, suggesting that degradation of starch by different α-amylases is a major factor affecting release of fluorescein from starch granules. Moreover, granule size of starch greatly affected enzymatic hydrolysis and controlled release in this system. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01059-2.

8.
Mol Ther ; 30(8): 2800-2816, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35526096

RESUMO

Several preclinical studies demonstrate that antitumor efficacy of programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade can be improved by combination with other checkpoint inhibitors. Lymphocyte-activation gene 3 (LAG-3) is an inhibitory checkpoint receptor involved in T cell exhaustion and tumor immune escape. Here, we describe ABL501, a bispecific antibody targeting LAG-3 and PD-L1 in modulating immune cell responses against tumors. ABL501 that efficiently inhibits both LAG-3 and PD-L1 pathways enhances the activation of effector CD4+ and CD8+ T cells with a higher degree than a combination of single anti-LAG-3 and anti-PD-L1. The augmented effector T cell responses by ABL501 resulted in mitigating regulatory-T-cell-mediated immunosuppression. Mechanistically, the simultaneous binding of ABL501 to LAG-3 and PD-L1 promotes dendritic cell (DC) activation and tumor cell conjugation with T cells that subsequently mounts effective CD8+ T cell responses. ABL501 demonstrates its potent in vivo antitumor efficacy in a humanized xenograft model and with knockin mice expressing human orthologs. The immune profiling analysis of peripheral blood reveals an increased abundance of LAG-3hiPD-1hi memory CD4+ T cell subset in relapsed cholangiocarcinoma patients after gemcitabine plus cisplatin therapy, which are more responsive to ABL501. This study supports the clinical evaluation of ABL501 as a novel cancer immunotherapeutic, and a first-in-human trial has started (NCT05101109).


Assuntos
Anticorpos Biespecíficos , Antígenos CD , Antígeno B7-H1 , Neoplasias , Animais , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos , Células Dendríticas , Camundongos , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1 , Evasão Tumoral , Proteína do Gene 3 de Ativação de Linfócitos
9.
J Shoulder Elbow Surg ; 31(7): 1488-1498, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35041969

RESUMO

BACKGROUND: The application of patient-specific instrumentation (PSI) for reverse total shoulder replacement has been rapidly increasing, which could reduce errors in implant positioning. Although PSI theoretically holds promise, evidence of the accuracy and reliability of PSI in shoulder replacement surgery is limited. METHODS: Thirty-nine shoulders that underwent reverse total shoulder arthroplasty were included in this study and categorized into two groups: the conventional (n = 20) and PSI (n = 19) groups. Screw (length and angle) and baseplate (version, inclination, translation, and rotation) positioning were calculated based on postoperative computed tomography images using a three-dimensional measurement tool. The difference between the values of the preoperative target and postoperative measurement was calculated to evaluate the reproducibility of preoperative planning. Screw involvement in the suprascapular and spinoglenoid notches was assessed. Thus, the correlation between the position of the baseplate and the screws was assessed. RESULTS: The mean differences between the planned length and angle (anteroposterior and superoinferior angles) and postoperative measurement in the PSI group were significantly smaller than those in the conventional group. Similarly, the mean difference in baseplate rotation between the planned and postoperative measurements in the PSI group was significantly lower than that in the conventional group (4.5° vs 10.6°; P < .001). The spinoglenoid notch was involved in 10 cases in the conventional group and 2 cases in the PSI group, and this difference was significant (P = .014). Overall, the mean difference between the preoperative and postoperative version, inferior inclination, and rotation values for the baseplate position was significantly correlated with the values for screw position (length and angle). CONCLUSIONS: PSI improves the reproducibility of preoperative planning for baseplate and screw positioning and reduces the risk of neurovascular injury in reverse total shoulder arthroplasty.


Assuntos
Artroplastia do Ombro , Artroplastia de Substituição , Articulação do Ombro , Artroplastia de Substituição/métodos , Artroplastia do Ombro/métodos , Humanos , Imageamento Tridimensional , Reprodutibilidade dos Testes , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia
10.
Food Sci Biotechnol ; 30(10): 1313-1319, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34721926

RESUMO

Food authenticity is one of the largest concerns in recent days. As kimchi has been a global food, its production origin has been important issue, particularly due to the large import from China. Among the potential methods, electronic nose which can measure volatile compounds in foods is considered to be a powerful device for identifying country of production. This study is to classify 69 kinds of kimchi produced in South Korea (39) and China (30) by analyzing volatile compounds in kimchi using electronic nose-mass spectrometry. Two widely used multivariate analyses, discriminant function analysis and principal component analysis, were used. Results showed that both multivariate analyses can completely separate Korean and Chinese kimchi using 10 kinds of molecular weights among 10-160 amu. The results indicate that the volatile compounds in kimchi are a suitable target to determine the geographical origin of kimchi.

11.
Food Sci Biotechnol ; 30(10): 1339-1346, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34721929

RESUMO

Fluorescein isothiocyanate-dextrans (FDs) of different molecular weights were infused into corn, waxy rice, tapioca, and potato starches under atmospheric and high hydrostatic pressures (HHP). FD4, FD10, FD20, and FD40 (Mw 4000, 10,000, 20,000, and 40,000, respectively) were used as infusion materials. Confocal laser scanning microscopy confirmed that all FDs except FD40 infused into corn, waxy rice, and tapioca starches. However, no FDs infused into potato starch. Corn starch had the highest amounts of infused FDs. As molar mass increased, the amount of infused FD decreased in all starches. The infused amounts of FDs in corn starch were similar at 200-300 MPa and atmospheric pressure. Infusion of FDs at 400 MPa was reduced due to partial gelatinization. These results confirm that infusion efficiency is inversely proportional to the molecular weight of the infused material and large materials (Mw > 40,000) cannot be infused into starch granules under atmospheric pressure or HHP. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00972-2.

12.
Pharmaceuticals (Basel) ; 14(10)2021 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-34681277

RESUMO

The mucin (MUC) family is a group of highly glycosylated macromolecules that are abundantly expressed in mammalian epithelial cells. MUC proteins contribute to the formation of the mucus barrier and thus have protective functions against infection. Interestingly, some MUC proteins are aberrantly expressed in cancer cells and are involved in cancer development and progression, including cell growth, proliferation, the inhibition of apoptosis, chemoresistance, metabolic reprogramming, and immune evasion. With their unique biological and structural features, MUC proteins have been considered promising therapeutic targets and also biomarkers for human cancer. In this review, we discuss the biological roles of the transmembrane mucins MUC1 and MUC16 in the context of hallmarks of cancer and current efforts to develop MUC1- and MUC16-targeted therapies.

13.
PLoS One ; 16(8): e0256404, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34415968

RESUMO

Dietary homogenization has progressed worldwide due to westernization and the globalization of food production systems. We investigated dietary heterogeneity in South Korea by examining the spatial distribution of carbon (C), nitrogen (N), and sulfur (S) isotope ratios using 264 human hair samples. Overall, variation in isotope values was small, indicating low dietary heterogeneity. We detected differences in δ13C, δ15N, and δ34S values between administrative provinces and metropolitan cities; inter-regional differences were typically < 1 ‰. Values of δ34S were significantly lower in hair samples from inland regions relative to those from coastal locations, and a similar pattern was observed in δ15N values. Understanding geographic variation in δ34S and δ15N values in human hair is useful for provenancing humans in South Korea.


Assuntos
Isótopos de Carbono , Isótopos de Nitrogênio , Isótopos de Enxofre , Humanos , República da Coreia
14.
Food Chem ; 356: 129705, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33836361

RESUMO

We developed and validated a method for the simultaneous quantitative analysis of food dyes in two food matrices, i.e., chewing gum and soft drinks. Furthermore, we evaluated the stability of food dyes in these matrices with respect to the pH and acid content. The optimized and validated method is based on high-performance liquid chromatography-photodiode array (HPLC-PDA) and liquid chromatography-tandem spectroscopy; the proposed method could identify and quantify 12 dyes in the two matrices. The recoveries of the food dyes identified by HPLC-PDA analysis ranged from 98.61% to 118.42%, with relative standard deviations of 0.06-4.90%. In addition, the expanded uncertainties of the measurements ranged from 0.57 to 3.12%. Finally, the food dyes were found to be stable in the matrices over 30 days. Thus, we believe that the proposed analytical method is suitable for the identification and quantification of food dyes in chewing gum and soft drink samples.


Assuntos
Bebidas Gaseificadas/análise , Goma de Mascar/análise , Corantes/análise , Análise de Alimentos/métodos , Cromatografia Líquida de Alta Pressão , Concentração de Íons de Hidrogênio , Limite de Detecção , Espectrometria de Massas em Tandem , Incerteza
15.
J Breast Cancer ; 24(2): 235-240, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33818018

RESUMO

Tumor localization in patients receiving neoadjuvant chemotherapy (NACT) is challenging because substantial therapeutic remission of the original tumor after NACT is often noted. Currently, there is no guidance device that allows for an accurate estimation of the resection range in breast-conserving surgery after NACT. To increase the accuracy of tumor resection, we used a 3-dimensional-printed breast surgical guide based on magnetic resonance imaging (MRI) in the supine position for a breast cancer patient who underwent breast-conserving surgery after NACT. Using this device, the breast tumor with apparent therapeutic changes after NACT on imaging was successfully removed with clear resection margins by identifying the original tumor site in the affected breast. Irrespective of whether the residual tumor area after NACT is well defined, it is possible to confirm and target the tumor area on pre-NACT MRI using this device.

16.
Neurospine ; 18(4): 871-879, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35000343

RESUMO

OBJECTIVE: The aims of this study were to describe the unilateral biportal endoscopic (UBE) technique for decompression of extraforaminal stenosis at L5-S1 and evaluate 1-year clinical outcomes. Especially, we evaluated compression factors of extraforaminal stenosis at L5-S1 and described the surgical technique for decompression in detail. METHODS: Thirty-five patients who underwent UBE decompression for extraforaminal stenosis at L5-S1 between March 2018 and February 2019 were enrolled. Clinical results were analyzed using the MacNab criteria, the visual analogue scale (VAS) for back and leg pain, and the Oswestry Disability Index (ODI). Compression factors evaluated pseudoarthrosis within the transverse process of L5 and ala of sacrum, disc bulging with or without osteophytes, and the thickened lumbosacral and extraforaminal ligament. RESULTS: The mean back VAS was 3.7 ± 1.8 before surgery, which dropped to 2.3 ± 0.8 at 1-year postoperative follow-up (p < 0.001). There was a significant drop in postoperative mean VAS for leg pain from 7.2 ± 1.1 to 2.3 ± 1.2 at 1 year (p < 0.001). The ODI was 61.5 before surgery and 28.6 (p < 0.001). Pseudoarthrosis between the transverse process and the ala was noted in all cases (35 of 35, 100%). Pure disc bulging was seen in 12 patients (34.3%), and disc bulging with osteophytes was demonstrated in 23 patients. The thickened lumbosacral and extraforaminal ligament were identified in 19 cases (51.4%). No complications occurred in any of the patients. CONCLUSION: In the current study, good surgical outcomes without complications were achieved after UBE decompression for extraforaminal stenosis at L5-S1.

17.
Bone Marrow Transplant ; 56(5): 1159-1170, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33279940

RESUMO

In patients with acute myeloid leukemia (AML) consolidation treatment options are between allogeneic hematopoietic stem cell transplantation (HCT) and chemotherapy, based on disease risk at the time of initial presentation and age. Measurable residual disease (MRD) following induction chemotherapy could be incorporated as a useful parameter for treatment decisions. The present study evaluated treatment outcomes according to the next-generation sequencing (NGS)-based MRD status and the type of consolidation therapy in patients with normal karyotype (NK)-AML. By sequencing 278 paired samples collected at diagnosis and first remission (CR1), we identified 361 mutations in 124 patients at diagnosis and tracked these at CR1. After excluding mutations associated with age-related clonal hematopoiesis, 82 mutations in 50 of the 124 patients (40.3%) were detected at CR1. Survival benefit was observed in favor of allogeneic HCT over chemotherapy consolidation in the MRDpos subgroup with respect to overall survival (HR 0.294, p = 0.003), relapse-free survival (HR 0.376, p = 0.015) and cumulative incidence of relapse (HR 0.279, p = 0.004) in multivariate analysis, but not in the MRDneg subgroup. In summary, these data support allogeneic HCT in NK-AML patients with detectable MRD by NGS in CR1. Randomized clinical trials will be required to confirm this observation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Neoplasia Residual , Prognóstico , Recidiva , Indução de Remissão , Transplante Homólogo
18.
Geriatr Orthop Surg Rehabil ; 11: 2151459320956958, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224551

RESUMO

INTRODUCTION: Importance of inferomedial supporting screws in preventing varus collapse has been investigated for the proximal humerus fracture. However, few studies reported the results of osteoporotic complex fracture. This study aimed to demonstrate the stress distribution pattern, particularly in osteoporotic 3-part proximal humerus fractures involving greater tuberosity (GT) with different screw configurations. MATERIALS AND METHODS: Using the computed tomography (CT) images of 2 patients, who had osteoporosis and the other had normal bone density, 3-part fractures involving the GT, without medial support were reconstructed. To reflect the osteoporosis or real bone density, Hounsfield unit of CT scans were utilized. A force of 200 N was applied in 30° varus direction. The proximal screws were set in 2 ways: 6 screws without inferomedial supporting screws and 9 screws with inferomedial supporting screws. Qualitative and quantitative analysis of internal stress distribution were performed. RESULTS: The most proximal part area near humeral head vertex and near the 1st screw's passage and tip had more stress concentrated in osteoporotic 3-part fractures. The stress distribution around the proximal screws was found near the GT fracture line and its lateral side, where the local max values located. Inferomedial supporting screws decreased these effects by changing the points to medial side from the GT. The ratio in osteoporotic bone model decreased to that in normal bone model when inferomedial supporting screws were applied (normal bone, 2.97%-1.30%; osteoporosis bone, 4.76%-1.71%). CONCLUSIONS: In osteoporotic 3-part proximal humerus fracture, the stress distribution was concentrated on the area near the humeral vertex, 1st row screw tips, and lateral side region from the GT fracture line. Moreover, inferomedial supporting screws ensured that the stress distribution is similar to that in normal bone setting, particularly in osteoporotic condition.

19.
Foods ; 9(6)2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32604920

RESUMO

The purpose of this study was to compare the nutritional components and antioxidant activities of two different cultivars of Brassica juncea (Dolsan, Yeosu, Korea (BJD) and (Jeongseon, Gangwon, Korea (BJJ)). We investigated the proximate composition (moisture, crude ash, crude protein and crude lipid), antioxidant activities (2,2-Diphenyl-2-picrylhydrazil (DPPH) scavenging activity and ferric reducing antioxidant power (FRAP)), total phenol content, total flavonoid content and sinigrin content by high-performance liquid chromatography analysis. Our results show that the proximate compositions of BJD and BJJ were not significantly different. However, both the DPPH radical scavenging and FRAP activities of the BJJ extracts were higher than those of the BJD extracts. The total phenol contents of the BJD and BJJ extracts were 6.56 and 9.80 mg gallic acid equivalent/g, respectively. The total flavonoids content of the BJD and BJJ extracts were 20.92 and 34.81 mg rutin equivalent/g, respectively, whereas the sinigrin contents, one of the major compounds in BJD and BJJ extracts, were 16.16 mg/g and 11.73 mg/g, respectively. In this study, we confirmed that, by comparing BJJ and BJD, the sinigrin content of BJD was higher than that of BJJ, but the antioxidant activity and phenol content of BJD were superior to that of BJJ.

20.
Sci Rep ; 10(1): 5392, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-32214155

RESUMO

Breast cancer is one of the major female health problems worldwide. Although there is growing evidence indicating that air pollution increases the risk of breast cancer, there is still inconsistency among previous studies. Unlike the previous studies those had case-control or cohort study designs, we performed a nationwide, whole-population census study. In all 252 administrative districts in South Korea, the associations between ambient NO2 and particulate matter 10 (PM10) concentration, and age-adjusted breast cancer mortality rate in females (from 2005 to 2016, Nmortality = 23,565), and incidence rate (from 2004 to 2013, Nincidence = 133,373) were investigated via multivariable beta regression. Population density, altitude, rate of higher education, smoking rate, obesity rate, parity, unemployment rate, breastfeeding rate, oral contraceptive usage rate, and Gross Regional Domestic Product per capita were considered as potential confounders. Ambient air pollutant concentrations were positively and significantly associated with the breast cancer incidence rate: per 100 ppb CO increase, Odds Ratio OR = 1.08 (95% Confidence Interval CI = 1.06-1.10), per 10 ppb NO2, OR = 1.14 (95% CI = 1.12-1.16), per 1 ppb SO2, OR = 1.04 (95% CI = 1.02-1.05), per 10 µg/m3 PM10, OR = 1.13 (95% CI = 1.09-1.17). However, no significant association between the air pollutants and the breast cancer mortality rate was observed except for PM10: per 10 µg/m3 PM10, OR = 1.05 (95% CI = 1.01-1.09).


Assuntos
Poluição do Ar/efeitos adversos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/mortalidade , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Variação Biológica da População/fisiologia , Neoplasias da Mama/etiologia , Exposição Ambiental/análise , Feminino , Humanos , Incidência , Dióxido de Nitrogênio/efeitos adversos , Dióxido de Nitrogênio/análise , Material Particulado/análise , Vigilância da População/métodos , República da Coreia/epidemiologia , Estações do Ano
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