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The aim of this study was to investigate the utilization of clove bud oil as fat-soluble antioxidants for retarding lipid oxidation in organogels by structuring canola oil with beeswax at 5, 7.5, and 10% concentration under accelerated oxidation condition. Oil binding capacity and viscoelastic properties were increased with beeswax content, but were not nearly affected by the addition of clove bud oil. Organogel loaded with clove bud oil were found to be more effective in retarding lipid oxidation in high beeswax content systems, particularly evident in 10% beeswax samples. The addition of clove bud oil resulted in low levels of hyeoperxide and MDA, and protected against texture and color deterioration during the storage period. Additionally, the Pearson correlation between lipid oxidation indices and parameters of texture and color has been found to exhibit a limited association, with the exception of the a* and b* values, which show a strong correlation.
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This study evaluated the effect of ultrasound using papain and sodium bicarbonate (SC) on meat tenderness to achieve the desired texture for elderly individuals. Meats were immersed in distilled water (DW) or papain (PI), ultrasonically treated with papain (UPI), or ultrasonically treated with papain and SC (UPIS). Response surface methodology was used to optimize the processing conditions with the lowest hardness, and the optimal conditions were determined as follows: 400 U/mL papain, ultrasonic for 30 min, and 4% SC. Hardness, color, and myofibrillar fragmentation index (MFI) were investigated. The hardness followed the order of DW (22.50 N), PI (18.62 N), UPI (12.08 N), and UPIS (7.16 N), and UPIS showed the highest MFI. Papain and SC affected the color of the meat. Overall, ultrasound-assisted treatment using papain and SC resulted in hardness levels of less than 7.8 N, which can be easily compressed by low tongue pressure.
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The sex-specific differences in the growth and population characteristics of the high-commercial-value sand crab Ovalipes punctatus were investigated in Korea. The estimated allometric growth between the sexes showed significant differences in all morphometric measurements. In the classification of growth types, carapace width-chela length exhibited positive and negative allometric growth in males and females, respectively. Carapace width-abdominal width showed positive relative growth in both sexes, and orbital spine width exhibited negative relative growth in both sexes. Consequently, sexual dimorphism was evident in all measured traits. Growth parameters estimated using the ELEFAN function of the FiSAT II program indicated higher values in males compared to females. Asymptotic length (CW∞) for males was estimated at 139.2 mm, whereas for females it was 116.6 mm. Additionally, the growth coefficient (K) was higher in males (0.65) than in females (0.54), suggesting faster growth in males. The winter point (WP) was 1 for males and 0.7 for females, indicating slower growth in males during the colder December and slower growth in females during the spawning period in August. The modified von Bertalanffy growth curves indicated asymptotic growth in all sexes, and the growth performance index (φ') showed higher values in males (4.10) compared to females (3.87), reflecting differences in growth curves. The steady increase in recruitment rates from July to September was associated with the appearance of larvae and their subsequent growth into juveniles, leading to their recruitment into the population during this period. Therefore, O. punctatus exhibited sex-specific differences in growth parameters, suggesting distinct growth strategies between the sexes.
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Caracteres Sexuales , Animales , Femenino , Masculino , República de Corea , Tamaño Corporal , Estaciones del Año , Braquiuros/crecimiento & desarrollo , Braquiuros/anatomía & histología , Braquiuros/fisiologíaRESUMEN
BACKGROUND: The overall survival rates among cancer patients have been improving. However, the increase in survival is not uniform across socioeconomic status. Thus, we investigated income disparities in the 5-year survival rate (5YSR) in cancer patients and the temporal trends. METHODS: This study used a national cancer cohort from 2002 to 2018 that was established by linking the Korea Central Cancer Registry and the National Health Insurance Service (NHIS) claim database to calculate the cancer survival rate by income level in the Republic of Korea. Survival data were available from 2002 onward, and the analysis was based on the actuarial method. We compared the survival of the earliest available 5-year period of 2002-2006 and the latest available 5-year period of 2014-2018, observing until 31 December 2021. Income level was classified into six categories: Medical Aid beneficiaries and five NHIS subtypes according to insurance premium. The slope index of inequality (SII) and relative index of inequality were used to measure absolute and relative differences in 5YSR by income, respectively. RESULTS: The 5YSR between the 2002-2006 and 2014-2018 periods for all cancers improved. A significant improvement in 5-year survival rates (5YSR) over the study period was observed in lung, liver, and stomach cancer. The SII of survival rates for lung (17.5, 95% confidence interval (CI) 7.0-28.1), liver (15.1, 95% CI 10.9-19.2), stomach (13.9, 95% CI 3.2-24.7), colorectal (11.4, 95% CI 0.9-22.0), and prostate (10.7, 95% CI 2.5-18.8) cancer was significantly higher, implying higher survival rates as income levels increased. The SII for lung, liver, and stomach cancer increased, while that of thyroid, breast, cervical, prostate, and colorectal cancer decreased over the study period. CONCLUSIONS: Although substantial improvement in the 5YSR was observed across cancer types and income levels from 2002 to 2018, this increase was not uniformly distributed across income levels. Our study revealed persistent income disparities in the survival of cancer patients, particularly for lung and liver cancer.
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OBJECTIVE: The increasing concern over adolescent suicide necessitates suicide prevention training for school teachers, as students spend a significant portion of their time at school. This study's objective is to develop a suicide prevention program tailored for teachers. METHODS: The program was developed by a multidisciplinary research team, drawing on a review of both domestic and international suicide prevention programs, related scholarly articles, and Korean psychological autopsy interviews of adolescents. This was complemented by a survey of teachers to assess the program's practicality and usability. RESULTS: The developed program comprises three parts, consistent with other versions: Careful Observation, Active Listening, and Risk Evaluation and Expert Referral. Careful Observation focuses on training teachers to recognize verbal, behavioral, and situational warning signs of suicidal ideation in students; Active Listening involves strategies for encouraging students to express their suicidal thoughts and techniques for being an empathetic and attentive listener; Risk Evaluation and Expert Referral provides instruction on how to assess suicide risk and assist students safely. CONCLUSION: It is anticipated that this program will equip teachers with valuable knowledge and skills, contributing to a reduction in adolescents suicide rates.
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Although proteomics is extensively used in immune research, there is currently no publicly accessible spectral assay library for the comprehensive proteome of immune cells. This study generated spectral assay libraries for five human immune cell lines and four primary immune cells: CD4 T, CD8 T, natural killer (NK) cells, and B cells. This was achieved by utilizing data-dependent acquisition (DDA) and employing fractionated samples from over 100 µg of proteins, which was applied to acquire the highest-quality MS/MS spectral data. In addition, Data-indedendent acquisition (DIA) was used to obtain sufficient data points for analyzing proteins from 10,000 primary CD4 T, CD8 T, NK, and B cells. The immune cell spectral assay library generated included 10,544 protein groups and 127,106 peptides. The proteomic profiles of 10,000 primary human immune cells obtained from 15 healthy volunteers analyzed using DIA revealed the highest heterogeneity of B cells among other immune cell types and the similarity between CD4 T and CD8 T cells. All data and spectral library are deposited in ProteomeXchange (PXD047742).
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Linfocitos B , Células Asesinas Naturales , Proteómica , Humanos , Células Asesinas Naturales/inmunología , Linfocitos B/inmunología , Proteoma/análisis , Espectrometría de Masas en Tándem , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunologíaRESUMEN
A significantly enhanced THz radiation generation from femtosecond photoexcited MoS2 layers due to Nb-doping is reported here. Different microscopic mechanisms involved in the THz photocurrent generation vary in their relative contributions in the two cases of photoexcitation, i.e., above and below the electronic bandgap of the layers. For a moderate Nb-doping level of just â¼0.05%, we have observed a multifold enhancement in the THz emission for the case of the above bandgap excitation, which is, though, nearly 1.5 times for the case of the below bandgap excitation of the monolayer MoS2. Alongside the difference in THz generation efficiency, the THz pulse polarity is also reversed at the above bandgap excitation of the Nb-doped layers, consequent to the reversed surface depletion field. Except for a slightly smaller difference in the THz enhancement factor, all the observations are reproducible in the bilayers as well to imply a weaker inversion symmetry and reduced screening of the surface depletion field due to Nb-doping. Furthermore, we employed pristine MoS2 and Nb-doped MoS2 monolayers to fabricate piezoelectric nanogenerator devices. Like enhancement in the ultrafast THz emission, the piezoelectric performance of the nanogenerator, fabricated with the Nb-doped MoS2 monolayer is also increased by a similar factor.
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INTRODUCTION: Holocarboxylase synthetase deficiency (HLCS deficiency, OMIM #253270) is an exceedingly rare metabolic disorder resulting in multiple carboxylase deficiencies owing to impaired biotin cycle. Clinical manifestations include severe metabolic acidosis, hyperammonemia, tachypnea, skin rash, alopecia, feeding problems, hypotonia, developmental delay, seizures, and, in severe cases, death. METHODS AND RESULTS: An 8-day-old female neonate presented with severe lactic acidosis, necessitating sedation and mechanical ventilation. Despite receiving supportive care, no evident clinical improvement was observed, accompanied by the onset of generalized ichthyosis. Genetic analysis of actionable metabolic disorders revealed compound heterozygous variants of HLCS (NM_000411.8), specifically c.[710T>C (p.Leu237Pro)]; [1544G>A (p.Ser515Asn)], prompting the initiation of biotin mega-dose therapy (10 mg/day). Remarkably, dramatic clinical improvement in lactic acidosis was observed the day after initiating biotin administration, leading to the discontinuation of mechanical ventilation within 6 days. The patient remained in stable condition during follow-up, exhibiting normal growth and development along with consistently stable laboratory findings up to 18 months of age. CONCLUSION: Our case highlights the significance of early genetic testing in neonates with unexplained metabolic disorders to enable timely diagnosis and therapy initiation. Biotin therapy has demonstrated remarkable efficacy in improving the clinical condition of patients with HLCS deficiency, leading to favorable outcomes.
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Biotina , Deficiencia de Holocarboxilasa Sintetasa , Humanos , Femenino , Recién Nacido , Biotina/uso terapéutico , Biotina/administración & dosificación , Deficiencia de Holocarboxilasa Sintetasa/genética , Deficiencia de Holocarboxilasa Sintetasa/tratamiento farmacológico , Acidosis Láctica/genética , Acidosis Láctica/tratamiento farmacológico , Complejo Vitamínico B/uso terapéutico , Complejo Vitamínico B/administración & dosificaciónRESUMEN
Purpose: This study aimed to report the overall national trends in the rates of cancer screening based on recommendations and provide insights into the changing trends of these rates across different demographics. Materials and Methods: This study used data from the Korean National Cancer Screening Survey (KNCSS), which surveys nationwide cancer-screening rates and includes 4,500 individuals meeting the Korean National Cancer Screening Program (NCSP) protocol age criteria. Cancer-screening rates were assessed using structured questionnaires; yearly trends were analyzed for both lifetime cancer-screening rates and rates of screening based on recommendations, and subgroup analyses were performed based on age and sex. Results: The rates of cancer screening based on recommendations showed significant increments: the stomach cancer-screening rate increased from 39.2% in 2004 to 77.5% in 2023 (3.50% per year), the liver cancer-screening rate increased from 20.0% to 48.8% (4.30% per year), and the colorectal cancer, increased from 19.9% to 70.7% (5.15% per year). The breast cancer-screening rate increased from 33.2% to 72.7% (2.88% per year), and the cervical cancer, increased from 58.3% to 70.2% (1.08% per year). Despite some differences, particularly in relation to sociodemographic factors, screening rates increased significantly for all cancer types. Conclusion: Cancer-screening rates in Korea increased consistently from 2004 to 2023, demonstrating the effectiveness of the national cancer-screening program. However, the increments in breast, cervical and lung cancer-screening rates were relatively lower, indicating the need for additional efforts and strategies.
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We developed emulsion-filled calcium alginate gels (EF-CAG) as a novel thermoresponsive carrier for plant-based meat analogs (PBMA), designed to mimic the cooking-induced flavor release of real meat. Optimized to maximize flavor release upon heating, EF-CAG demonstrated a thermoresponsive release of 51% with a notable size reduction. Initial release profiles varied between media; a burst release of 43% occurred in water within the first 5 min, while <1% was released in air. EF-CAG consistently increased flavor release in PBMA during cooking, without adversely affecting appearance or flavor stability, maintaining flavor retention at 4 °C for 10 days. The sensory evaluation confirmed that EF-CAG successfully masked the beef flavor before cooking and enhanced its release afterward. Our findings suggest that EF-CAG can be effectively used as a flavoring agent for PBMA, offering similar flavor attributes to real meat during cooking.
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BACKGROUND: We aimed to describe the clinical and microbiological characteristics of enterococcal bacteremia, as well as the effect of Enterococcus resistance against vancomycin on clinical outcomes in Korean children. METHODS: We retrospectively reviewed the medical records of children diagnosed with enterococci isolated from blood cultures at Pusan National University Children's Hospital between December 2009 and November 2021. RESULTS: In total, 64 patients were enrolled in the study. The median age was 0 years (range 0-15), and 43 (67.2%) patients were male. Enterococcus faecalis (50%) was the most commonly identified bacterial strain. Significant underlying diseases were present in 60 patients (93.8%), and the source of bacteremia was identified in 36 patients (56.3%). Among these, intravascular device was the most common identifiable source. Fifty-six (87.5%) patients had previously received broad-spectrum antibiotics and 54 (84.4%) patients were nosocomial in origin. Twenty-nine (45.3%) strains were resistant to ampicillin, and 16 (25%) strains were resistant to vancomycin. All patients with vancomycin-resistant enterococci (VRE) had underlying disease (P = 0.199), and focus of bacteremia was significantly more frequent in VRE patients (P = 0.014). Of all the patients, after appropriate antibiotic treatment, five (7.8%) patients had recurrent enterococcal bacteremia, and seven (10.9%) patients were diagnosed with bacteremia, defined as other pathogens from blood culture. The 30-day mortality rate was 7.8%. CONCLUSION: Enterococcal bacteremia in children is usually nosocomial and occurs in children with serious underlying diseases. Because the number of enrolled patients and mortality were small in our study, it is difficult to identify whether the factor that determines prognosis in patients with enterococcal bacteremia is VRE or an underlying disease. Further studies with a large number of patients in a specific group are needed.
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Background: In South Korea, the cancer incidence rate has increased by 56.5% from 2001 to 2021. Nevertheless, the 5-year cancer survival rate from 2017 to 2021 increased by 17.9% compared with that from 2001 to 2005. Cancer survival rates tend to decline with lower socioeconomic status, and variations exist in the survival rates among different cancer types. Analyzing socioeconomic patterns in the survival of patients with cancer can help identify high-risk groups and ensure that they benefit from interventions. Objective: The aim of this study was to analyze differences in survival rates among patients diagnosed with six types of cancer-stomach, colorectal, liver, breast, cervical, and lung cancers-based on socioeconomic status using Korean nationwide data. Methods: This study used the Korea Central Cancer Registry database linked to the National Health Information Database to follow up with patients diagnosed with cancer between 2014 and 2018 until December 31, 2021. Kaplan-Meier curves stratified by income status were generated, and log-rank tests were conducted for each cancer type to assess statistical significance. Hazard ratios with 95% CIs for any cause of overall survival were calculated using Cox proportional hazards regression models with the time since diagnosis. Results: The survival rates for the six different types of cancer were as follows: stomach cancer, 69.6% (96,404/138,462); colorectal cancer, 66.6% (83,406/125,156); liver cancer, 33.7% (23,860/70,712); lung cancer, 30.4% (33,203/109,116); breast cancer, 91.5% (90,730/99,159); and cervical cancer, 78% (12,930/16,580). When comparing the medical aid group to the highest income group, the hazard ratios were 1.72 (95% CI 1.66-1.79) for stomach cancer, 1.60 (95% CI 1.54-1.56) for colorectal cancer, 1.51 (95% CI 1.45-1.56) for liver cancer, 1.56 (95% CI 1.51-1.59) for lung cancer, 2.19 (95% CI 2.01-2.38) for breast cancer, and 1.65 (95% CI 1.46-1.87) for cervical cancer. A higher deprivation index and advanced diagnostic stage were associated with an increased risk of mortality. Conclusions: Socioeconomic status significantly mediates disparities in cancer survival in several cancer types. This effect is particularly pronounced in less fatal cancers such as breast cancer. Therefore, considering the type of cancer and socioeconomic factors, social and medical interventions such as early cancer detection and appropriate treatment are necessary for vulnerable populations.
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Neoplasias , Humanos , República de Corea/epidemiología , Femenino , Neoplasias/mortalidad , Neoplasias/epidemiología , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Anciano , Tasa de Supervivencia/tendencias , Disparidades en el Estado de Salud , Factores Socioeconómicos , Estudios de Cohortes , Sistema de Registros , Clase Social , Disparidades Socioeconómicas en SaludRESUMEN
OBJECTIVES: To synthesize quantitative research findings on the prevalence and risk factors for in-hospital mortality of patients on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: A comprehensive search was conducted for the period from May 2008 to December 2023 by searching the five electronic databases of PubMed, CINAHL, Web of Science, EMBASE, and Cochrane library. The quality of included studies was assessed using the Newcastle-Ottawa scale. The meta-analysis estimated the pooled odds ratio or standard mean difference and 95% confidence intervals. RESULTS: A total of twenty-five studies with 10,409 patients were included in the analysis. The overall in-hospital mortality of patients on VA-ECMO was 56.7 %. In the subgroup analysis, in-hospital mortality of VA-ECMO for cardiogenic shock and cardiac arrest was 49.2 % and 75.2 %, respectively. The number of significant factors associated with an increased risk of in-hospital mortality in the pre-ECMO period (age, body weight, creatinine, chronic kidney disease, pH, and lactic acid) was greater than that in the intra- and post-ECMO periods. Renal replacement, bleeding, and lower limb ischemia were the most significant risk factors for in-hospital mortality in patients receiving VA-ECMO. CONCLUSION: Early detection of the identified risk factors can contribute to reducing in-hospital mortality in patients on VA-ECMO. Intensive care unit nurses should provide timely and appropriate care before, during, and after VA-ECMO. IMPLICATIONS FOR CLINICAL PRACTICE: Intensive care unit nurses should be knowledgeable about factors associated with the in-hospital mortality of patients on VA-ECMO to improve outcomes. The present findings may contribute to developing guidelines for reducing in-hospital mortality among patients considering ECMO.
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Non-alcoholic fatty liver disease (NAFLD), prevalent among conditions like obesity and diabetes, is globally significant. Existing ultrasound diagnosis methods, despite their use, often lack accuracy and precision, necessitating innovative solutions like AI. This study aims to validate an AI-enhanced quantitative ultrasound (QUS) algorithm for NAFLD severity assessment and compare its performance with Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF), a conventional diagnostic tool. A single-center cross-sectional pilot study was conducted. Liver fat content was estimated using an AI-enhanced quantitative ultrasound attenuation coefficient (QUS-AC) of Barreleye Inc. with an AI-based QUS algorithm and two conventional ultrasound techniques, FibroTouch Ultrasound Attenuation Parameter (UAP) and Canon Attenuation Imaging (ATI). The results were compared with MRI-PDFF values. The intraclass correlation coefficient (ICC) was also assessed. Significant correlation was found between the QUS-AC and the MRI-PDFF, reflected by an R value of 0.95. On other hand, ATI and UAP displayed lower correlations with MRI-PDFF, yielding R values of 0.73 and 0.51, respectively. In addition, ICC for QUS-AC was 0.983 for individual observations. On the other hand, the ICCs for ATI and UAP were 0.76 and 0.39, respectively. Our findings suggest that AC with AI-enhanced QUS could serve as a valuable tool for the non-invasive diagnosis of NAFLD.
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Blood coagulation mediated by pig tissue factor (TF), which is expressed in pig tissues, causes an instant blood-mediated inflammatory reaction during pig-to-human xenotransplantation. Previously, we generated a soluble pig tissue factor pathway inhibitor α fusion immunoglobulin (TFPI-Ig) which inhibits pig TF activity more efficiently than human TFPI-Ig in human plasma. In this study, we generated several pig TFPI-Ig mutants and tested the efficacy of these mutants in preventing pig-to-human xenogeneic blood coagulation. Structurally important amino acid residues of pig TFPI-Ig were changed into different residues by site-directed mutagenesis. Subsequently, a retroviral vector encoding each cDNA of several pig TFPI-Ig mutants was cloned and transduced into CHO-K1 cells. After establishing stable cell lines expressing each of the pig TFPI-Ig mutants, soluble proteins were produced and purified for evaluating their inhibitory effects on pig TF-mediated blood coagulation in human plasma. The replacement of K36 and K257 with R36 and H257, respectively, in pig TFPI-Ig more efficiently blocked pig TF activity in human plasma when compared with the wild-type pig TFPI-Ig. These results may provide additional information to understand the structure of pig TFPIα, and an improved pig TFPI-Ig variant that more efficiently blocks pig TF-mediated blood coagulation during pig-to-human xenotransplantation.
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Coagulación Sanguínea , Lipoproteínas , Trasplante Heterólogo , Animales , Humanos , Porcinos , Lipoproteínas/genética , Lipoproteínas/metabolismo , Coagulación Sanguínea/genética , Células CHO , Cricetulus , Tromboplastina/genética , Tromboplastina/metabolismo , Mutagénesis Sitio-Dirigida , Análisis Mutacional de ADNRESUMEN
In this study, changes in bioactive compound contents and the in vitro biological activity of mixed grains, including oats, sorghum, finger millet, adzuki bean, and proso millet, with eight different blending ratios were investigated. The total phenolic compounds and flavonoid contents ranged from 14.43-16.53 mg gallic acid equivalent/g extract and 1.22-5.37 mg catechin equivalent/g extract, respectively, depending on the blending ratio. The DI-8 blend (30% oats, 30% sorghum, 15% finger millet, 15% adzuki bean, and 10% proso millet) exhibited relatively higher antioxidant and anti-diabetic effects than other blending samples. The levels of twelve amino acids and eight organic acids in the grain mixes were measured. Among the twenty metabolites, malonic acid, asparagine, oxalic acid, tartaric acid, and proline were identified as key metabolites across the blending samples. Moreover, the levels of lactic acid, oxalic acid, and malonic acid, which are positively correlated with α-glucosidase inhibition activity, were considerably higher in the DI-blending samples. The results of this study suggest that the DI-8 blend could be used as a functional ingredient as it has several bioactive compounds and biological activities, including anti-diabetic activity.
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Antioxidantes , Grano Comestible , Antioxidantes/farmacología , Antioxidantes/química , Grano Comestible/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Flavonoides/análisis , Flavonoides/química , Flavonoides/farmacología , Fenoles/análisis , Extractos Vegetales/farmacología , Extractos Vegetales/química , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Aminoácidos/metabolismo , Aminoácidos/análisisRESUMEN
Hypertension remains a significant global health concern, contributing significantly to cardiovascular diseases and mortality rates. The inhibition of angiotensin-converting enzyme (ACE) plays a crucial role in alleviating high blood pressure. We investigated the potential of finger millets (Eleusine coracana) as a natural remedy for hypertension by isolating and characterizing its ACE-inhibitory compound. First, we evaluated the ACE-inhibitory activity of the finger millet ethanol extract and subsequently proceeded with solvent fractionation. Among the solvent fractions, the ethyl acetate fraction exhibited the highest ACE inhibitory activity and was further fractionated. Using preparative high-performance liquid chromatography, the ethyl acetate fraction was separated into four subfractions, with fraction 2 (F2) exhibiting the highest ACE inhibitory activity. Subsequent 1 H-nuclear magnetic resonance (NMR) and 13 C-NMR analyses confirmed that the isolated compound from F2 was catechin. Furthermore, molecular docking studies indicated that catechin has the potential to act as an ACE inhibitor. These findings suggest that finger millets, particularly as a source of catechin, have the potential to be used as a natural antihypertensive.
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Inhibidores de la Enzima Convertidora de Angiotensina , Antihipertensivos , Eleusine , Simulación del Acoplamiento Molecular , Extractos Vegetales , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/química , Eleusine/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antihipertensivos/farmacología , Antihipertensivos/química , Cromatografía Líquida de Alta Presión , Peptidil-Dipeptidasa A/metabolismo , Hipertensión/tratamiento farmacológico , Espectroscopía de Resonancia MagnéticaRESUMEN
ATP-binding cassette transporter B6 (ABCB6), a protein essential for heme biosynthesis in mitochondria, also functions as a heavy metal efflux pump. Here, we present cryo-electron microscopy structures of human ABCB6 bound to a cadmium Cd(II) ion in the presence of antioxidant thiol peptides glutathione (GSH) and phytochelatin 2 (PC2) at resolutions of 3.2 and 3.1 Å, respectively. The overall folding of the two structures resembles the inward-facing apo state but with less separation between the two halves of the transporter. Two GSH molecules are symmetrically bound to the Cd(II) ion in a bent conformation, with the central cysteine protruding towards the metal. The N-terminal glutamate and C-terminal glycine of GSH do not directly interact with Cd(II) but contribute to neutralizing positive charges of the binding cavity by forming hydrogen bonds and van der Waals interactions with nearby residues. In the presence of PC2, Cd(II) binding to ABCB6 is similar to that observed with GSH, except that two cysteine residues of each PC2 molecule participate in Cd(II) coordination to form a tetrathiolate. Structural comparison of human ABCB6 and its homologous Atm-type transporters indicate that their distinct substrate specificity might be attributed to variations in the capping residues situated at the top of the substrate-binding cavity.
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Transportadoras de Casetes de Unión a ATP , Humanos , Transportadoras de Casetes de Unión a ATP/química , Transportadoras de Casetes de Unión a ATP/metabolismo , Transportadoras de Casetes de Unión a ATP/ultraestructura , Sitios de Unión , Cadmio/metabolismo , Cadmio/química , Microscopía por Crioelectrón , Glutatión/metabolismo , Glutatión/química , Modelos Moleculares , Fitoquelatinas/metabolismo , Fitoquelatinas/química , Unión Proteica , Conformación ProteicaRESUMEN
BACKGROUND: Spinal anesthesia-induced hypotension (SAH) frequently occurs in older patients, many of whom have mild left ventricular (LV) diastolic dysfunction, often asymptomatic at rest. This study investigated the association between preoperative echocardiographic measurements and SAH in older patients with mild LV diastolic dysfunction. METHODS: We conducted a retrospective observational study using data from electronic medical records. The patients ≥ 65 years old who underwent spinal anesthesia for urologic surgery between January 2016 and December 2017 and whose preoperative echocardiography within 6 months before surgery revealed grade I LV diastolic dysfunction were recruited. SAH was investigated using the anesthesia records. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: A total of 163 patients were analyzed. SAH and significant SAH developed in 55 (33.7%) patients. The mitral inflow E velocity was an independent risk factor for SAH (odds ratio [OR], 0.886; 95% confidence interval [CI], 0.845-0.929; P < 0.001). The area under the ROC curve for mitral inflow E velocity to predict SAH was 0.819 (95% CI, 0.752-0.875; P < 0.001). If mitral inflow E velocity was ≤ 60 cm/s, SAH was predicted with a sensitivity of 83.6% and specificity of 70.4%. CONCLUSIONS: The preoperative mitral inflow E velocity demonstrated the greatest predictability of SAH in older patients with mild LV diastolic dysfunction. This may assist in identifying patients at high risk of SAH and guiding preventive strategies in the future.