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Tumor heterogeneity and drug resistance have been invincible features of cancer for its complete cure. Despite the advent of immunotherapy, the expansion and diversification of cancer cells evolved even in the absence or presence of drug treatment discourage additional therapeutic interventions. For the eradication of cancer cells, therefore, an 'all-at-once' strategy is required, which exploits both target-selective chemotherapy and non-selective physicotherapy. Multifactorial microcapsules comprising gold nanoparticles (AuNPs) and a self-assembly protein of α-synuclein (αS) were fabricated, in which hydrophobic and hydrophilic drugs could be separately encapsulated by employing lipid-based inverted micelles (IMs). Their combined physico-chemical therapeutic effects were examined since they also contained both membrane-disrupting IMs and heat-generating AuNPs upon irradiation as physicotherapeutic agents. For the optimal enclosure of IMs containing hydrophilic drugs, a porous inner skeleton made of poly(lactic-co-glycolic acid) was introduced, which would play the roles of not only compartmentalizing the internal space but also enhancing proteolytic disintegration of the microcapsules to discharge and stabilize IMs to the outside. In fact, hydrophobic paclitaxel and hydrophilic doxorubicin showed markedly enhanced drug efficacy when delivered in the IM-containing microcapsules exhibiting the 'quantal' release of both drugs into the cells whose integrity could be also affected by the IMs. In addition, the remnants of αS-AuNP microcapsules produced via proteolysis also caused cell death through photothermal effect. The multifactorial microcapsules are therefore considered as a promising anti-cancer drug carrier capable of performing combinatorial selective and non-selective chemical and physical therapies to overcome tumor heterogeneity and drug resistance.
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Doxorrubicina , Portadores de Fármacos , Ouro , Nanopartículas Metálicas , Neoplasias , Paclitaxel , Ouro/química , Humanos , Portadores de Fármacos/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Doxorrubicina/química , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Nanopartículas Metálicas/química , Nanopartículas Metálicas/administração & dosagem , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , alfa-Sinucleína , Interações Hidrofóbicas e Hidrofílicas , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Micelas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Linhagem Celular Tumoral , CápsulasRESUMO
Non-small cell lung cancer (NSCLC) accounts for 85 % of all lung cancers. In NSCLC, 10-20 % of Caucasian patients and 30-50 % of Asian patients have tumors with activating mutations in the Epidermal Growth Factor Receptor (EGFR). A high percentage of these patients exhibit favorable responses to treatment with tyrosine kinase inhibitors (TKI). Unfortunately, a majority of these patients develop therapeutic resistance with progression free survival lasting 9-18 months. The mechanisms that underlie the tumorigenic effects of EGFR and the ability of NSCLC to develop resistance to TKI therapies, however, are poorly understood. Here we demonstrate that CHI3L1 is produced by EGFR activation of normal epithelial cells, transformed epithelial cells with wild type EGFR and cells with cancer-associated, activating EGFR mutations. We also demonstrate that CHI3L1 auto-induces itself and feeds back to stimulate EGFR and its ligands via a STAT3-dependent mechanism(s). Highly specific antibodies against CHI3L1 (anti-CHI3L1/FRG) and TKI, individually and in combination, abrogated the effects of EGFR activation on CHI3L1 and the ability of CHI3L1 to stimulate the EGFR axis. Anti-CHI3L1 also interacted with osimertinib to reverse TKI therapeutic resistance and induce tumor cell death and inhibit pulmonary metastasis while stimulating tumor suppressor genes including KEAP1. CHI3L1 is a downstream target of EGFR that feeds back to stimulate and activate the EGFR axis. Anti-CHI3L1 is an exciting potential therapeutic for EGFR mutant NSCLC, alone and in combination with osimertinib or other TKIs.
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Determining the genetic diversity and source rookeries of sea turtles collected from feeding grounds can facilitate effective conservation initiatives. To ascertain the genetic composition and source rookery, we examined a partial sequence of the mitochondrial control region (CR, 796 bp) of 40 green turtles (Chelonia mydas) collected from feeding grounds around the Korean Peninsula between 2014 and 2022. We conducted genetic and mixed-stock analyses (MSA) and identified 10 CR haplotypes previously reported in Japanese populations. In the haplotype network, six, three, and one haplotype(s) grouped with the Japan, Indo-Pacific, and Central South Pacific clades, respectively. The primary rookeries of the green turtles were two distantly remote sites, Ogasawara (OGA) and Central Ryukyu Island (CRI), approximately 1,300 km apart from each other. Comparing three parameters (season, maturity, and specific feeding ground), we noted that OGA was mainly associated with summer and the Jeju Sea, whereas CRI was with fall and the East (Japan) Sea ground. The maturity did not show a distinct pattern. Our results indicate that green turtles in the feeding grounds around the Korean Peninsula originate mainly from the Japan MU and have genetic origins in the Japan, Indo-Pacific, and Central South Pacific clades. Our results provide crucial insights into rookeries and MUs, which are the focus of conservation efforts of the Republic of Korea and potential parties to collaborate for green turtle conservation.
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Haplótipos , Tartarugas , Animais , Tartarugas/genética , República da Coreia , Variação Genética/genética , DNA Mitocondrial/genética , Migração Animal , Comportamento Alimentar , Estações do Ano , Conservação dos Recursos NaturaisRESUMO
Verifying habitats, including the foraging and nesting areas for sea turtles, enables an understanding of their spatial ecology and successful planning of their conservation and management strategies. Recently, the observation frequency and bycatch of loggerhead (Caretta caretta) and green (Chelonia mydas) turtles have increased in the northern limit of their distribution range, in the northern part of the East China Sea and East (Japan) Sea. We conducted satellite tracking to investigate the habitat use of seven loggerhead and eight green turtles from June 2016 to August 2022 in this area, where little is known about their spatial ecology. We applied a 50 percent volume contour method to determine their main foraging areas and analyzed 6 environmental variables to characterize their habitats. Loggerhead turtles mainly stayed in and used the East China Sea as a foraging area during the tracking period, while two individuals among them also used the East Sea as a seasonal foraging area. Most green turtles also used the East China Sea as a foraging area, near South Korea and Japan, with one individual among them using the lower area of the East Sea as a seasonal foraging area. Notably, one green turtle traveled to Hainan Island in the South China Sea, a historical nesting area. Our results showed that the two sea turtle species included the East Sea as a seasonal foraging area, possibly owing to the abundance of food sources available, despite its relatively lower sea temperature. Considering that loggerhead and green sea turtles were observed using the northern part of the East China Sea and East Sea more frequently than previously known and that the sea temperature gradually increases due to climate change, conservation and management activities are required for sea turtles in these areas.
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Tartarugas , Humanos , Animais , Oceano Pacífico , Ecossistema , Ecologia , TemperaturaRESUMO
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease resulting in irreversible scarring within the lungs. However, the lack of biomarkers that enable real-time assessment of disease activity remains a challenge in providing efficient clinical decision-making and optimal patient care in IPF. Fibronectin (FN) is highly expressed in fibroblastic foci of the IPF lung where active extracellular matrix (ECM) deposition occurs. Functional upstream domain (FUD) tightly binds the N-terminal 70-kilodalton domain of FN that is crucial for FN assembly. In this study, we first demonstrate the capacity of PEGylated FUD (PEG-FUD) to target FN deposition in human IPF tissue ex vivo. We subsequently radiolabeled PEG-FUD with 64Cu and monitored its spatiotemporal biodistribution via µPET/CT imaging in mice using the bleomycin-induced model of pulmonary injury and fibrosis. We demonstrated [64Cu]Cu-PEG-FUD uptake 3 and 11 days following bleomycin treatment, suggesting that radiolabeled PEG-FUD holds promise as an imaging probe in aiding the assessment of fibrotic lung disease activity.
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Fibrose Pulmonar Idiopática , Humanos , Animais , Camundongos , Distribuição Tecidual , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/metabolismo , Pulmão/diagnóstico por imagem , Pulmão/metabolismo , Peptídeos/metabolismo , BleomicinaRESUMO
The mitogenome of a soft coral, Eleutherobia rubra (Brundin, 1896), was completely sequenced for the first time. The total mitogenome length of E. rubra is 18,724 bp with 14 protein-coding genes, two ribosomal RNA genes, one transfer RNA gene (tRNA-Met), and one non-coding region (NCR). The gene order is also consistent with other Alcyoniidae species. The base composition is 30.1% A, 16.7% C, 19.5% G, and 33.7% T, with a G-C content of 36.2%. This is the first record of the complete mitogenome sequence of the genus Eleutherobia.
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The Korean Triage and Acuity Scale (KTAS) is used to determine emergency patient priority. The purpose of this study was to develop the Competency-Based Triage Education Application (CTEA) using KTAS and evaluate its effectiveness on emergency nurses' triage competency and performance. The developed CTEA mobile application comprised 4 lectures, 12 text-based cases, and 8 video-based triage scenarios. A quasi-experimental pre-post design with a comparison group (CG) was used to evaluate the effectiveness of the CTEA. Thirty-one participants were assigned to an intervention group (IG) and used the application for at least 100 min over one week. Thirty-five participants were assigned to a CG and underwent book-based learning, which covered the same content as the CTEA. Triage competency (t = 2.55, p = 0.013) and performance (t = 2.11, p = 0.039) were significantly improved in the IG. The IG's undertriage error was significantly reduced compared to that of the CG (t = 2.08, p = 0.041). These results indicated that the CTEA was effective in improving the emergency nurses' triage competency and performance. This application will be useful as a program for providing repeated and continuous triage education.
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Anemia is associated with physical, cognitive, and developmental problems. Given that there are limited studies on anemia prevalence among obese Asian adolescents and that past evidence is controversial, this study investigated the relationship between obesity and anemia in a nationally representative sample of South Korean adolescents. Data were obtained from the 2007-2019 Korea National Health and Nutrition Examination Survey. Overall, 10,231 subjects were included in the analysis. Multiple logistic regression was performed to determine the relationship between obesity and anemia. Compared with the non-obesity group, the adjusted odds ratio (OR; 95% confidence interval [CI]) of anemia was 1.00 (0.66-1.50) in the obesity group. However, in the early adolescent subgroup of 10-13 years (adjusted OR, 2.88; 95% CI, 1.20-6.95), the risk of anemia was significantly higher in the obese group than in the non-obese group. Obesity was associated with an increased risk of anemia in early adolescents. Obese adolescents aged 10-13 require special care, especially through regular examination and management for anemia.
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With most sea turtle populations declining, activities to conserve their habitat and nesting grounds and restore their populations are being implemented worldwide. To preserve the Northwestern Pacific populations, the National Marine Biodiversity Institute of Korea has been releasing artificially propagated sea turtles, but whether these individuals join the wild population remains unknown. The present study aimed to determine the movement patterns of artificially propagated juvenile loggerhead (Caretta caretta) and green (Chelonia mydas) turtles fitted with satellite transmitters on their carapaces and released in the waters of Jeju or Yeosu, Republic of Korea, between August 2018 and April 2022. Loggerheads traveled northward to the East Sea, whereas green turtles moved west or southwest. Two 36-month-old and two 48-month-old loggerheads moved toward their potential nursery grounds and toward their feeding grounds, respectively. Three green turtles with a curved carapace length (CCL) of <40 cm moved toward their nursery or feeding grounds, while three individuals (CCL > 45 cm) moved toward their inshore foraging areas. The travel paths were closely related to the direction of local sea currents. Our results implied that releasing artificially propagated sea turtles, considering their age and CCL, can positively contribute to the conservation of Northwestern Pacific populations.
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Recent health care developments have emphasized person-centered care, which highlights individualized treatments rather than focusing solely on the nature of a given disease. Thus, we aim to identify the factors and construct a structural equation model for developing person-centered care competency among senior nursing students based on the social cognitive career theory and a subsequent literature review. We use a hypothetical model to examine the factors influencing person-centered care competency, and using a structured questionnaire, and we collect data on self-awareness, the clinical learning environment, clinical practicum adaptation, nursing professionalism, empathy, and person-centered care competency. The participants include 383 third- and fourth-year senior nursing students who had undergone at least one semester of clinical practice in South Korea. SPSS/WIN 26.0 is used to analyze all obtained data, while AMOS 25.0 is used for structural equation modeling. The final model is confirmed to be suitable for explaining and predicting person-centered care competency among participants. Nursing professionalism, empathy, clinical practicum adaptation, self-awareness, and the clinical learning environment explained 38.8% of the total variance among participants. Strategies and interventions designed to enhance person-centered care competency for senior nursing students should particularly focus on nursing professionalism, empathy, clinical practicum adaptation, self-awareness, and the clinical learning environment.
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Bacharelado em Enfermagem , Estudantes de Enfermagem , Humanos , Assistência Centrada no Paciente , Preceptoria , República da CoreiaRESUMO
BACKGROUND: Mytilus coruscus Gould, 1861 is a mussel species in the family Mytilidae, native to the Northwest Pacific Ocean, ranging from the East China Sea, the Yellow Sea, and as far as the Peter the Great Gulf in the East Sea. In Korea, this species has been heavily exploited for nutrient-rich food resources and experienced severe reduction in their population. OBJECTIVE: The aim of this study was to investigate the genetic diversity and population structure and to provide baseline data to facilitate the conservation and sustainable use of the vulnerable species M. coruscus in South Korea. METHODS: Mitochondrial DNA (mtDNA) cytochrome c oxidase I (COI) sequences of 91 adult individuals from four islands and one coastal localities in South Korea were sequenced. We then compared genetic diversity and haplotype data with previously published Chinese wild populations. RESULTS: Mytilus coruscus populations on Korean coasts were found to exhibit high genetic diversity despite concerns regarding recent population reduction. A total of 42 haplotypes were defined by 56 polymorphic sites. High-level genetic diversity was observed on four Island sites (Hd = 0.906-0.955, π = 0.0068-0.0090). The other seashore site represented relatively lower genetic diversity (Hd = 0.529, π = 0.0011) and was genetically differentiated from the others. In a previous study, wild populations on the East China Sea exhibited similarly high genetic diversity as that observed in our study. Additionally, Chinese M. coruscus populations exhibit a distinct regional haplotype distribution pattern while sharing six haplotypes with Korean populations. CONCLUSIONS: The results of this study provide insights that further the current understanding regarding the evolution of M. coruscus species and provides comprehensive genetic data to facilitate the development of an effective conservation strategy.
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Bivalves/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Mitocôndrias/enzimologia , Mytilus/genética , Animais , Bivalves/enzimologia , DNA Mitocondrial/genética , Variação Genética/genética , Genética Populacional , Haplótipos/genética , Humanos , Repetições de Microssatélites/genética , Mytilus/enzimologia , Filogenia , República da CoreiaRESUMO
In this study, we provide the first report of the complete mitochondrial genomic sequencing of a yellow-bellied sea snake (Hydrophis platurus) that has the broadest distribution range of all Squamata species. The mitogenome length was 18,101 bp and consisted of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and 3 non-coding regions. The sequence presented could be very useful for further phylogenetic and evolutionary studies.
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The complete mitogenome of the Sclreractinia, Montipora efflorescens Bernard, 1897 was sequenced for the first time. It had 17,887 bp, with 13 protein-coding genes, and two rRNA and two tRNA genes. Composition of M. efflorescens mitogenome was identical to that of typical Scleractinians. In conclusion, the complete mitogenome may provide detailed information on coral phylogeny.
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The complete mitochondrial genome of sand-hopper Trinorchestia longiramus was analyzed in this study, which is the first for the genus within the family Talitridae. The mitogenome sequence is 15,401 bp in length containing two ribosomal RNA genes, 22 transfer RNA genes, 13 protein-coding genes, and a control region as found in most amphipods. The gene order showed that T. longiramus has a unique control region location compared to other amphipods. Phylogenetic analysis using the maximum likelihood method positioned T. longiramus within the monophyletic clades of the family Talitridae.
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In this study, we provide the first report of the complete mitochondrial genome of Emydocephalus ijimae. The mitogenome length is 18,259 bp and includes 13 protein-coding genes, two rRNA genes, 22 tRNA genes, and three non-coding regions. The sequence presented could be very useful for further phylogenetic and evolutionary study.
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Here, for the first time, we sequenced the complete mitogenome of Alveopora japonica Eguchi, 1968 (Scleractinia: Acroporidae). Genome size was 17,886 bp with 13 protein-coding, two rRNA, and two tRNA genes. This gene composition was identical to the typical scleractinian pattern. Our results strongly support the recent transfer of this coral species to the family Acroporidae.
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The full-length mitochondrial genome of the triton trumpet Charonia lampas (Linnaeus, 1758) was analyzed by the primer walking method. Its mitogenome is 15,382 bp in length, comprising 13 protein-coding genes, two ribosomal RNA genes, and 22 transfer RNA genes. The gene order of C. lampas is congruent with those previously reported for the infraorder Littorinimorpha. This is the first full-length mitogenome sequence for the genus Charonia. In the phylogenetic tree, C. lampas formed a monophyletic group with the other species of the superfamily Tonnoidea, but did not show the closest phylogenetic relationship to a species from the same family, Ranellidae.
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The mitochondrial genome of the gastropod Auriculastra duplicata was completely sequenced. It was 13,920 bp in length and comprised 37 genes; two rrn genes and 22 trn genes. Phylogenetic analyses based on the concatenated protein-coding genes depicted the polyphyly of all species belonging to the family Ellobiidae; however, monophyly was observed among all species belonging to the subfamily Ellobiinae, in which A. duplicata clustered consistently with Auriculinella bidentata.
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A probiotic is a viable microbial dietary supplement that has beneficial effects such as prevention and treatment of specific gastrointestinal disorders, including counteracting gut barrier dysfunction associated with inflammation and infection. Probiotic Bacillus polyfermenticus, which is commonly called Bispan strain, has been appropriately used for the treatment of long-term intestinal disorders. The use of B. polyfermenticus for immune-related chronic intestinal disease may be appropriate considering that about 80% of the body's immune system is localized in the gastrointestinal tract. The current study aimed to evaluate the effect of probiotic B. polyfermenticus on the immune response of human subjects through the quantification of immune cell population and serum levels of immunoglobulins (Igs). Twenty-five male subjects, 20-35 years of age, were randomly assigned to either a control group (n =12) supplemented with a placebo or the experimental group (n = 13) supplemented with B. polyfermenticus tablets at a dose of 3.1 x 10(8) colony-forming units/day for 8 weeks. Dietary intake analyses from 3-day dietary records from three consecutive days including one weekend day and two weekdays revealed no significant differences in total energy and nutrient intakes between the two groups. The humoral immune response was monitored by the number of total B lymphocytes and serum concentrations of IgG, IgA, and IgM. To investigate the changes in immune cell populations, percentages of total T lymphocytes, CD4+ helper T cells, CD8+ cytotoxic T cells, and CD56+ natural killer (NK) cells were quantified. The concentration of IgG in the experimental group was 12% higher than in the placebo group after 8 weeks of Bispan supplementation. Also, the percentages of CD4+ helper T cells, CD8+cytotoxic T cells, and CD56+ NK cells in the Bispan strain-supplemented group were 32%, 28%, and 35% higher, respectively, compared with the control group. Because of a higher increment of the CD4+ T cell subset than CD8+ T cells, the ratio of CD4+/CD8+ T cells was greater in the experimental group. This study suggests that the supplementation of B. polyfermenticus has a potentially positive effect on immune function by enhancing IgG production as well as by modulating the number of immune cell population such as CD4+ and CD8+ T cells and NK cells.
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Bacillus , Suplementos Nutricionais , Imunoglobulina G/sangue , Células Matadoras Naturais/imunologia , Probióticos/administração & dosagem , Linfócitos T/imunologia , Adulto , Linfócitos B/imunologia , Dieta , Humanos , Imunoglobulina A/sangue , Imunoglobulina M/sangue , Contagem de Linfócitos , Subpopulações de Linfócitos/imunologia , Masculino , Placebos , Linfócitos T Citotóxicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologiaRESUMO
This study focused on the preparation of resveratrol nanocarrier systems and the evaluation of their in vitro antibacterial activities. Gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) for resveratrol nanocarrier systems were synthesized using green synthetic routes. During the synthesis steps, resveratrol was utilized as a reducing agent to chemically reduce gold and silver ions to AuNPs and AgNPs. This system provides green and eco-friendly synthesis routes that do not involve additional chemical reducing agents. Resveratrol nanocarriers with AuNPs (Res-AuNPs) and AgNPs (Res-AgNPs) were observed to be spherical and to exhibit characteristic surface plasmon resonance at 547 nm and at 412-417 nm, respectively. The mean size of the nanoparticles ranged from 8.32 to 21.84 nm, as determined by high-resolution transmission electron microscopy. The face-centered cubic structure of the Res-AuNPs was confirmed by high-resolution X-ray diffraction. Fourier-transform infrared spectra indicated that the hydroxyl groups and C=C in the aromatic ring of resveratrol were involved in the reduction reaction. Res-AuNPs retained excellent colloidal stability during ultracentrifugation and re-dispersion, suggesting that resveratrol also played a role as a capping agent. Zeta potentials of Res-AuNPs and Res-AgNPs were in the range of -20.58 to -48.54 mV. Generally, against Gram-positive and Gram-negative bacteria, the Res-AuNPs and Res-AgNPs exhibited greater antibacterial activity compared to that of resveratrol alone. Among the tested strains, the highest antibacterial activity of the Res-AuNPs was observed against Streptococcus pneumoniae. The addition of sodium dodecyl sulfate during the synthesis of Res-AgNPs slightly increased their antibacterial activity. These results suggest that the newly developed resveratrol nanocarrier systems with metallic nanoparticles show potential for application as nano-antibacterial agents with enhanced activities.