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The aberrant assembly of amyloid-ß (Aß) is implicated in Alzheimer's disease (AD). Recent clinical outcomes of Aß-targeted immunotherapy reinforce the notion that clearing Aß burden is a potential therapeutic approach for AD. Herein, to develop drug candidates for chemically driven clearance of Aß aggregates, we synthesized 51 novel polyfunctionalized furo[2,3-b:4,5-b']dipyridine-chalcone hybrid compounds. After conducting two types of cell-free anti-Aß functional assays, Aß aggregation prevention and Aß aggregate clearance, we selected YIAD-0336, (E)-8-((1H-pyrrol-2-yl)methylene)-10-(4-chlorophenyl)-2,4-dimethyl-7,8-dihydropyrido[3',2':4,5]furo[3,2-b]quinolin-9(6H)-one, for further in vivo investigations. As YIAD-0336 exhibited a low blood-brain barrier penetration profile, it was injected along with aggregated Aß directly into the intracerebroventricular region of ICR mice and ameliorated spatial memory in Y-maze tests. Next, YIAD-0336 was orally administered to 5XFAD transgenic mice with intravenous injections of mannitol, and YIAD-0336 significantly removed Aß plaques from the brains of 5XFAD mice. Collectively, YIAD-0336 dissociated toxic aggregates in the mouse brain and hence alleviated cognitive deterioration. Our findings indicate that chemically driven clearance of Aß aggregates is a promising therapeutic approach for AD.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Modelos Animales de Enfermedad , Ratones Transgénicos , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Ratones , Péptidos beta-Amiloides/metabolismo , Chalcona/química , Chalcona/farmacología , Chalcona/análogos & derivados , Chalconas/química , Chalconas/farmacología , Chalconas/administración & dosificación , Masculino , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Humanos , Memoria/efectos de los fármacos , Agregado de Proteínas/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Piridinas/química , Piridinas/farmacología , Piridinas/administración & dosificaciónRESUMEN
Chemicals have been identified as a potential risk factor of renal dysfunction. However, studies that consider both multiple chemicals and non-chemical risk factors, such as hypertension, are rare. In this study, we assessed the associations between exposure to several chemicals, including major metals, phthalates, and phenolic compounds, and the albumin-to-creatinine ratio (ACR). A group of Korean adult women in reproductive age (n = 438, aged between 20 and 49 years), who had previously been studied for association of several organic chemicals, was chosen for this purpose. We constructed multivariable linear regression models for individual chemicals and weighted-quantile sum (WQS) mixtures, by hypertension status. Among the study population, approximately 8.5% of the participants exhibited micro/macro-albuminuria (ACR ≥30 mg/g), and 18.5% and 3.9% exhibited prehypertension and hypertension, respectively. Blood cadmium and lead levels showed a stronger association with ACR only among women with prehypertension or hypertension. Among organic chemicals, depending on the statistial model, benzophenone-1 (BP-1) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) showed a significant association regardless of hypertension status, but most associations disappeared in the (pre)hypertensive group. These findings clearly indicate that hypertension status can modify and may potentiate the association of environmental chemicals with ACR. Our observations suggest that low-level environmental pollutant exposure may have potential adverse effects on kidney function among general adult women. Considering the prevalence of prehypertension in the general population, efforts to reduce exposure to cadmium and lead are necessary among adult women to minimize the risk of adverse kidney function.
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Contaminantes Ambientales , Hipertensión , Ácidos Ftálicos , Prehipertensión , Adulto , Humanos , Femenino , Adulto Joven , Persona de Mediana Edad , Plomo/toxicidad , Creatinina , Cadmio , Prehipertensión/inducido químicamente , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/toxicidad , Contaminantes Ambientales/análisis , Ácidos Ftálicos/toxicidad , Hipertensión/inducido químicamente , Hipertensión/epidemiología , AlbúminasRESUMEN
BACKGROUND: Access to healthcare services is important, especially for patients with chronic diseases. We evaluated the effect of the COVID-19 pandemic on outpatient visits and medication for patients with hypertension and diabetes in South Korea. METHODS: Nationwide claims data were extracted for patients with hypertension and diabetes from January 2019 to July 2020. We used an interrupted time series (ITS) analysis to evaluate the pandemic's impact on outpatient care using the number of outpatient visits and days of medication supplied per visit. We identified the change in the continuity of care in medication, a consequence of the change in outpatient care, using the Medication Possession Ratio (MPR). RESULTS: The number of outpatient visits for diabetes significantly declined in February 2020, when community transmission began. However, when high-intensity social distancing was relaxed in April 2020, outpatient visits for hypertension and diabetes rebounded significantly. Moreover, when the outpatient visits declined, the number of days of medication supplied per visit increased. Consequently, the average MPRs significantly increased compared to 2019, increasing the ratio of patients with appropriate medication supply (MPR ≥ 0.8). CONCLUSIONS: Outpatient visits decreased immediately when COVID-19 spread to local communities. However, the number of days of medication supplied per visit increased to compensate for the longer intervals between visits. Rather, the change in the continuity of care in medication improved; thus, the temporary decrease in outpatient visits might have had a limited negative impact on health outcomes.
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COVID-19 , Diabetes Mellitus , Hipertensión , Humanos , Análisis de Series de Tiempo Interrumpido , Pandemias , Diabetes Mellitus/terapia , Diabetes Mellitus/tratamiento farmacológico , Atención Ambulatoria , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiologíaRESUMEN
Arsenic (As) exposure has been extensively studied by investigating As species (e.g., inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)) in urine, yet recent research suggests that blood could be a possible biomarker of As exposure. These investigations, however, were conducted on iAs-contaminated areas, and evidence on populations exposed to low levels of iAs is limited. This study aimed to describe the levels and distributions of As species in urine and blood, as well as to estimate methylation efficiency and related factors in the Korean population. Biological samples were obtained by the Korean Ministry of Food and Drug Safety. A total of 2025 urine samples and 598 blood samples were utilized in this study. Six As species were measured using ultra-high-performance liquid chromatography with inductively coupled plasma mass spectrometry (UPLC-ICP-MS): As(V), As(III), MMA, DMA, arsenobetaine (AsB), and arsenocholine (AsC). Multiple linear regression models were used to examine the relationship between As species (concentrations and proportions) and covariates. AsB was the most prevalent species in urine and blood. The relative composition of iAs, MMA, DMA, and AsC in urine and blood differed significantly. Consumption of blue-backed fish was linked to higher levels of AsB in urine and blood. Type of drinking water and multigrain rice consumption were associated with increased iAs concentration in urine. Except for iAs, every species had correlations in urine and blood in both univariate and multivariate analyses. Adolescents and smokers presented a lower methylation efficiency (higher %MMA and lower %DMA in urine) and females presented a higher methylation efficiency (lower %iAs, %MMA, and higher %DMA in urine). In conclusion, blood iAs concentration cannot represent urinary iAs; nonetheless, different compositions of urine and blood might reflect distinct information about iAs exposure. Further investigations on exposure factors and health are needed using low-exposure groups.
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Arsénico , Arsenicales , Agua Potable , Animales , Arsénico/análisis , Arsenicales/análisis , Ácido Cacodílico/orina , Cromatografía Líquida de Alta Presión , Agua Potable/análisis , Femenino , República de CoreaRESUMEN
Persistent organic pollutants (POPs) can disrupt the thyroid hormone system in humans. We assessed the associations of several POPs with serum thyroid hormones (T3 and T4) and thyroid-stimulating hormone, and investigated the modulating effects of sex, menopausal status, and age on these associations, in a subgroup of the adult population (n = 1250) from the Korean National Environmental Health Survey. PCB105 and PCB118 were negatively associated with total T4 in premenopausal females and males aged <50, whereas the associations were insignificant in other groups. PCB180, p,p'-DDE, and p,p'-DDT showed positive associations with total T3 in postmenopausal females; however, among males aged ≥50, PCB118, PCB138, and p,p'-DDE showed negative associations with total T3. The effects of exposure to multiple POPs were examined in multi-factor analyses. Factor 2 comprised PCB52, hexachlorobenzene, and BDE-47 was associated with an increase in free T4 in premenopausal females (ß = 0.015, p = 0.024), while Factor 1, which contained most POPs, was associated with a change in total T3 in postmenopausal females (ß = 0.032, p = 0.040) and males aged ≥50 (ß = -0.039, p = 0.023). Changes in total T4 or total T3 could be explained by differences in thyroxine-binding globulin (TBG) and peripheral deiodinase activity (GD). Negative associations of TBG with PCB105 in premenopausal females and PCB153 in males aged <50 may mediate the effect of decreasing total T4. PCB180, p,p'-DDE, p,p'-DDT, and Factor 1 were positively associated with GD, which is consistent with an increased total T3 in postmenopausal females. PCB118 was negatively associated with GD and total T3 in males aged ≥50. BDE-47 and ß-hexachlorocyclohexane were associated with thyroid autoantibodies in premenopausal females and males aged <50. Our observations suggest that the thyroid-disrupting effects of POPs may differ by sex, sex hormonal status, and age, and may be mediated by TBG and GD.
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Contaminantes Ambientales , Yoduro Peroxidasa , Hormonas Tiroideas , Globulina de Unión a Tiroxina , Adulto , Estudios Transversales , DDT/efectos adversos , Diclorodifenil Dicloroetileno/efectos adversos , Contaminantes Ambientales/efectos adversos , Femenino , Humanos , Yoduro Peroxidasa/metabolismo , Masculino , Menopausia , Persona de Mediana Edad , Contaminantes Orgánicos Persistentes/efectos adversos , Bifenilos Policlorados/efectos adversos , República de Corea , Hormonas Tiroideas/sangre , Globulina de Unión a Tiroxina/análisisRESUMEN
BACKGROUND: Associations of heavy metal exposures with obesity and obesity-related traits have been suggested, while those with nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM) are often inconsistent. METHODS: This study included 3787 adults aged ≥19 years who participated in the Korean National Environmental Health Survey 2015-2017, and investigated the association of toxic heavy metals with metabolic diseases. Lead (Pb), mercury (Hg), and cadmium (Cd) were measured either in urine (uHg, uCd) or total blood (bPb, bHg). Body mass index (BMI) was calculated, and DM cases were identified through a self-answered medication history. Hepatic Steatosis Index (HSI) as a surrogating index of NAFLD, was calculated using hepatic enzyme measurements, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT). RESULTS: Adults in the highest quartile of bPb, bHg, and uHg showed significantly elevated odds of obesity (BMI ≥25 kg/m2), compared to the lowest quartile (OR 1.58 for bPb, 1.92 for bHg, and 1.81 for uHg). HSI was positively correlated with bHg, uHg, and uCd concentrations. The odds of NAFLD (HSI ≥36) were also increased with increasing quartile of bHg, uHg, and uCd concentrations. For DM, bPb showed a significant negative association, while bHg and uCd exhibited non-monotonic and inconclusive associations. CONCLUSIONS: Among the general adult population of Korea, both Pb and Hg exposures were associated with an increased risk of obesity. In addition, both Hg and Cd exposures were associated with increased odds of NAFLD. These metals, however, were not associated with an increased risk of DM.
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Diabetes Mellitus , Mercurio , Adulto , Cadmio/toxicidad , Diabetes Mellitus/inducido químicamente , Diabetes Mellitus/epidemiología , Salud Ambiental , Humanos , Plomo , Mercurio/toxicidad , Obesidad/inducido químicamente , Obesidad/epidemiología , República de Corea/epidemiologíaRESUMEN
Urine was used as a part of a human biomonitoring study based on the excretion kinetics of less-persistent contaminants, such as phthalates and bisphenol A (BPA). Despite the advantages of being non-invasive and easy to collect, urine can show a large variability of concentrations of phthalate metabolites and BPA within a person depending on sampling time. Therefore, it is essential to assess the variability of urinary concentrations for comprehensive sampling design in the context of exposure and risk assessments. In this study, 18 phthalate metabolites and eight BPs were measured in all spot urine (n = 401) collected from 12 participants for seven consecutive days to evaluate within- and between-person variabilities. The intraclass correlation coefficients (ICCs) for all spot urines were poor for monomethyl phthalate (ICC: 0.002) and BPA (0.121) but were moderate for monoethyl phthalate (0.514) and monobenzyl phthalate (0.462). Based on the results of di (2-ethylhexyl) phthalate (DEHP) metabolites, the half-life and differences in metabolic capability seem to affect the ICCs. Urinary mono (2-ethylhexyl) phthalate (MEHP), a primary metabolite of DEHP, was suggested as a short-term exposure marker of DEHP in our study. Creatinine- and specific gravity-adjusted concentrations of phthalate metabolites and BPs resulted in increased ICCs, implying requirements for randomly collected spot urine. Most analytes in the first morning voids (FMVs) were correlated significantly with those in the daily composites, suggesting the feasibility of FMVs to estimate the daily exposure dose. This study facilitates a more comprehensive sampling design and data interpretation strategy for human biomonitoring studies.
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Dietilhexil Ftalato , Contaminantes Ambientales , Ácidos Ftálicos , Compuestos de Bencidrilo , Monitoreo Biológico , Dietilhexil Ftalato/orina , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/orina , Humanos , Fenoles , Ácidos Ftálicos/orinaRESUMEN
AIM: To investigate the outcomes and the effect sizes of ethical leadership in nursing practice. BACKGROUND: Many meta-analysis of ethical leadership have been conducted in other fields, but there are none for the effects of ethical leadership of nurse leaders and should be investigated. EVALUATION: For a systematic literature review, we searched PubMed, EMBASE, the Cochrane Library, CINAHL, OVID, Web of Science and Korean databases for studies published in Korean or English. We used Comprehensive Meta-Analysis (CMA) 2.0 and R 3.6.2 for the meta-analysis. KEY ISSUES: We divided the outcomes of ethical leadership into three categories and investigated the effect sizes: subordinates' perceptions of their leaders (ES = 0.65), subordinates' ethical behaviours (ES = 0.04) and job or organisational outcomes (ES = 0.45). In addition, we identified 14 outcome variables, and transformational leadership showed the greatest effect size (ES = 0.77) among them. CONCLUSION: This study confirmed the positive effects of ethical nursing leadership on individual nurses' perceptions about their leaders, their jobs and organisations. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing organisations and nurse administrators should make efforts to highlight ethical leadership of nurse leaders to improve outcomes of organisational performance including individual nurses' perceptions about their leaders, their jobs and organisations.
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Ética en Enfermería , Enfermeras Administradoras , Humanos , Liderazgo , Principios MoralesRESUMEN
A new domino mode of assembly was discovered from the one-pot three-component reactions of pyrrole derivatives, active methylene compounds (malononitrile, methyl cyanoacetate, or ethyl cyanoacetate), and sodium cyanide in the presence of piperidinium acetate in EtOH at room temperature, leading to a novel tricyclic skeleton in excellent yield under mild and eco-friendly conditions. This well-choreographed domino process enabled formation of multiple bonds (three C-C and one C-O) for consecutive construction of two rings (pyrrolidine and dihydrofuran) in a diastereoselective manner.
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Pirroles , Estructura MolecularRESUMEN
A DABCO catalyzed aza-Michael addition of thiazolidine-2,4-dione to a variety of electron deficient alkenes has been developed. Additionally, a DABCO/succinic acid salt system has been designed that allows for the one pot tandem aza-Michael/Knoevenagel reaction of thiazolidine-2,4-dione to give difunctionalized thiazolidine-2,4-dione products. To the best of our knowledge, this is the first example of a one-pot tandem aza-Michael/Knoevenagel reaction involving thiazolidine-2,4-dione.
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Alquenos , Ácido Succínico , Catálisis , Electrones , Estructura Molecular , Piperazinas , Tiazolidinedionas , TiazolidinasRESUMEN
The reaction of ß-ketonitrile and N-substituted pyrrole-2-carboxaldehyde in the presence of piperidinium acetate in CH3CN permitted regioselective access to 5-acylindolizine-7-carbonitrile through a domino Knoevenagel condensation-intramolecular aldol cyclization sequence. A wide range of new indolizine derivatives with a poly-functionalized pyridine moiety were readily synthesized in an atom-economical fashion, thereby expanding the indolizine chemical space for further applications.
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Due to dilution status of the urine, chemical concentrations measured in spot urine are frequently adjusted using correction factors, such as creatinine, specific gravity (SG), or osmolarity of the urine. Urinary correction factors, however, can be influenced dramatically by physiological changes such as pregnancy. Details about the variation of urine dilution over the course of pregnancy are not well characterized. In the present study, we investigated the variation of urine correction factors over time among the pregnant women of Korea (n = 69) and Thailand (n = 102). Creatinine, SG, and osmolality were determined in the urine samples obtained in each trimester of the participating women, and were compared by sampling time and by nationality. Implication of the variation in these correction factors was studied using phthalate metabolites measured in the urine samples as model chemicals. Urinary correction factors significantly varied across the trimesters especially in Korean pregnant women: urinary creatinine and osmolality were significantly lower in the third trimester (T3) urine than the first trimester (T1) urine. Urinary creatinine and SG of the T3 urine of Korean pregnant women were also significantly lower than those reported from the non-pregnant women who participated in Korean National Environmental Health Survey (KoNEHS) 2015-2017. Among Thai women, however, these correction factors were rather stable across the pregnancy. Differences in ethnicity, or in behavior such as water consumption amount may partly explain the differences. Temporal changes in these urine correction factors influenced the urinary phthalate metabolite concentrations adjusted for dilution, in both Korean and Thai pregnant women. The present observations show that the variations of urinary correction factors should be considered in exposure assessment of urinary chemicals for pregnant women, in order to circumvent potential bias due to physiological changes occurring during pregnancy, and to reduce errors in exposure classification and association.
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Contaminantes Ambientales , Ácidos Ftálicos , Creatinina , Femenino , Humanos , Concentración Osmolar , Embarazo , Mujeres Embarazadas , República de Corea , Gravedad Específica , TailandiaRESUMEN
Exposure to endocrine disrupting chemicals is suggested to be responsible for the development or progression of uterine fibroids. However, little is known about risks related to emerging chemicals, such as organophosphate esters (OPEs) and alternative plasticizers (APs). A case-control study was conducted to investigate whether exposures to OPEs, APs, and phthalates, were associated with uterine fibroids in women of reproductive age. For this purpose, the cases (n = 32) and the matching controls (n = 79) were chosen based on the results of gynecologic ultrasonography among premenopausal adult women in Korea and measured for metabolites of several OPEs, APs, and major phthalates. Logistic regression models were employed to assess the associations between chemical exposure and disease status. Factor analysis was conducted for multiple chemical exposure assessments as a secondary analysis. Among OPE metabolites, diphenyl phosphate (DPHP), 2-ethylhexyl phenyl phosphate (EHPHP), and 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) were detected in >80% of the subjects. Among APs, metabolites of di-isononyl phthalate (DINP) and di(2-propylheptyl) phthalate (DPrHpP) were detected in >75% of the urine samples. The odds ratios (ORs) of uterine fibroids were significantly higher among the women with higher exposures to tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-butoxyethyl) phosphate (TBOEP), di(2-ethylhexyl) terephthalate (DEHTP), DPrHpP, and di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH). In addition, urinary concentrations of mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), a sum of five di(2-ethylhexyl) phthalate metabolites (∑5DEHP), and mono(4-methyl-7-hydroxyoctyl) phthalate (OH-MINP) were significantly higher in the cases. In factor analysis, a factor heavily loaded with DPrHpP and DEHP was significantly associated with uterine fibroids, supporting the observation from the single chemical regression model. We found for the first time that several metabolites of OPEs and APs are associated with increased risks of uterine fibroids among pre-menopausal women. Further epidemiological and mechanistic studies are warranted to validate the associations observed in the present study.
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Leiomioma , Ácidos Ftálicos , Adulto , Estudios de Casos y Controles , Exposición a Riesgos Ambientales/análisis , Ésteres , Femenino , Humanos , Leiomioma/inducido químicamente , Organofosfatos/toxicidad , Plastificantes/análisis , Plastificantes/toxicidad , República de CoreaRESUMEN
Gemfibrozil, a lipid-regulating pharmaceutical, has been widely used for treating dyslipidemia in humans and detected frequently in freshwater environments. Since plasma cholesterol is a precursor of steroid hormones, the use of gemfibrozil may influence the sex hormone balances. However, its endocrine toxicity following long-term exposure is not well understood. The purpose of the present study is to investigate the effects of gemfibrozil on sex hormones and reproductive outcomes in a freshwater fish, following a long-term (155 d) exposure. For this purpose, Japanese medaka embryos (F0) were exposed to a series of gemfibrozil concentrations, i.e., 0, 0.04, 0.4, 3.7, and 40â¯mg/L for 155 d, and reproductive parameters, sex hormones, and associated gene expressions were assessed. For comparison, a short-term exposure (21 d) was performed separately with adult medaka and measured for sex hormones and related gene expressions. Following the 155 d long-term exposure, the fecundity showed a decreasing pattern. In addition, at 3.7â¯mg/L gemfibrozil, testosterone (T) level in the female fish was significantly decreased, and the hatchability of F1 fish was significantly decreased. The estrogen receptor (er) or vitellogenin (vtg) genes in gonads and liver were up-regulated. However, plasma cholesterol levels did not show significant changes in both sexes. The observations from the short-term (21 d) exposure were different from those of the long-term exposure. Following the short-term exposure, decreased 17ß-estradiol (E2), and 11-ketotestosterone (11-KT) levels along with decrease plasma cholesterol were observed in the male fish. The hormone disruption following the short-term exposure appears to be associated with the hypocholesterolemic activity of gemfibrozil. Our results show that the mechanisms of gemfibrozil toxicity may depend on the exposure duration. Consequences of long-term exposure to other fibrates in the water environment warrant further investigations.
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Gemfibrozilo/toxicidad , Hipolipemiantes/toxicidad , Oryzias/fisiología , Reproducción/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Animales , Colesterol/sangre , Femenino , Proteínas de Peces/genética , Hormonas Esteroides Gonadales/sangre , Gónadas/efectos de los fármacos , Gónadas/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Receptores de Estrógenos/genética , Vitelogeninas/genéticaRESUMEN
Probing spatial variation of temperature at the nanoscale provides key information for exploring diverse areas of modern science and technology. Despite significant progress in the development of contact thermometers with high spatial resolution, one inherent disadvantage is that the quantitative analysis of temperature can be complicated by the direct thermal contact. On the other hand, noncontact infrared radiation thermometer is free from such contact-induced disturbance, but suffers from insufficient spatial resolution stemming from diffraction-limit in the micrometer range. Combining a home-built sensitive infrared microscope with a noncontact scattering probe, we detected fluctuating electromagnetic evanescent fields on locally heated material surface, and thereby mapped temperature distribution in subwavelength scales. We visualize nanoscale Joule heating on current-carrying metal wires and find localized "hot-spots" developing along sharp corners of bended wires in the temperature mapping. Simulation calculations give quantitative account of the nanoscale temperature distribution, definitely indicating that the observed effect is caused by the nonuniform energy dissipation due to the current-crowding effect. The equipment in this work is a near-field version of infrared radiation thermometer with a spatial resolution far below the detection wavelength (<100 nm, or λ/140) in which local temperature distribution of operating nanoscale devices can be noninvasively mapped with a temperature resolution â¼2 K at room-temperature.
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We evaluated the clinical characteristics, cytokine/chemokine concentrations, viral shedding and antibody kinetics in 30 patients with Middle East respiratory syndrome (MERS), including 6 non-survivors admitted to 3 MERS-designated hospitals. Old age, low albumin, altered mentality and high pneumonia severity index score at admission were risk factors for mortality. In addition, severe signs of inflammation at initial presentation (at hospital days 1-4), such as high inducible protein-10 (p=0.0013), monocyte chemoattractant protein-1 (p=0.0007) and interleukin 6 (p=0.0007) concentrations, and poor viral control (high viral load at hospital days 5-10, p<0.001) without adequate antibody titres (low antibody titre at hospital days 11-16, p=0.07) during the course of disease, were associated with mortality.
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Anticuerpos Antivirales/sangre , Infecciones por Coronavirus/mortalidad , Citocinas/sangre , Carga Viral/genética , Coronavirus/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
The role of eating frequency (EF) in obesity development has been debated, and few studies have investigated Asian populations. Diet quality might affect the association between EF and obesity. Therefore, we investigated the association between EF and obesity indicators in a representative sample of Korean adults with consideration to diet quality. This cross-sectional study used data of 6951 participants aged 19-93 years (male 49·8 %, female 50·2 %) from the Fourth Korean National Health and Nutrition Examination Survey. EF was assessed using a questionnaire, and diet quality was defined as mean adequacy ratio (MAR). To explore the association between EF and obesity indicators, we used multiple linear regression analyses with and without interaction terms between diet quality and EF. EF was inversely associated with each obesity indicator, including body fat percentage (BF%), BMI and waist circumference (WC), showing a significant linear trend (P<0·001 for BF%, WC and BMI). In addition, the association between EF and each obesity indicator was significantly altered according to diet quality (P value of the interaction term EF×diet quality=0·008 in the regression model for BF%, <0·001 for BMI and 0·043 for WC). In the stratified analyses according to diet quality, EF had a significant inverse association with BF%, WC and BMI in the high diet quality groups, but not in the low diet quality groups. This study suggests that EF is inversely associated with the obesity indicators when diet quality is high, but not when it is low in Korean adults.
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Índice de Masa Corporal , Dieta/normas , Ingestión de Alimentos/fisiología , Circunferencia de la Cintura , Tejido Adiposo , Adulto , Anciano , Anciano de 80 o más Años , Composición Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , República de Corea , Adulto JovenRESUMEN
Inflammation mediated by the innate immune system is an organism's protective mechanism against infectious environmental risk factors. It is also a driver of the pathogeneses of various human diseases, including cancer development and progression. Microalgae are increasingly being focused on as sources of bioactive molecules with therapeutic potential against various diseases. Furthermore, the antioxidant, anti-inflammatory, and anticancer potentials of microalgae and their secondary metabolites have been widely reported. However, the underlying mechanisms remain to be elucidated. Therefore, in this study, we investigated the molecular mechanisms underlying the anti-inflammatory and anticancer activities of the ethanol extract of the Antarctic freshwater microalga Micractinium sp. (ETMI) by several in vitro assays using RAW 264.7 macrophages and HCT116 human colon cancer cells. ETMI exerted its anti-inflammatory activity by modulating the main inflammatory indicators such as cyclooxygenase (COX)-2, interleukin (IL)-6, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and nitric oxide (NO) in a dose-dependent manner. In addition, ETMI exerted cytotoxic activity against HCT116 cells in a dose-dependent manner, leading to significantly reduced cancer cell proliferation. Further, it induced cell cycle arrest in the G1 phase through the regulation of hallmark genes of the G1/S phase transition, including CDKN1A, and cyclin-dependent kinase 4 and 6 (CDK4 and CDK6, respectively). At the transcriptional level, the expression of CDKN1A gradually increased in response to ETMI treatment while that of CDK4 and CDK6 decreased. Taken together, our findings suggest that the anti-inflammatory and anticancer activities of the Antarctic freshwater microalga, Micractinium sp., and ETMI may provide a new clue for understanding the molecular link between inflammation and cancer and that ETMI may be a potential anticancer agent for targeted therapy of colorectal cancer.
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Antineoplásicos/farmacología , Inflamación/tratamiento farmacológico , Microalgas/química , Extractos Vegetales/farmacología , Regiones Antárticas , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Ciclooxigenasa 2 , Etanol , Agua Dulce , Humanos , Lipopolisacáridos , Macrófagos/efectos de los fármacos , Óxido Nítrico , Óxido Nítrico Sintasa de Tipo II , Factor de Necrosis Tumoral alfaRESUMEN
Background: We evaluated the diagnostic usefulness of polymerase chain reaction (PCR) analysis for detecting varicella-zoster virus (VZV) infection and reactivation of VZV, using DNA extracted from saliva and plasma specimens obtained from subjects with suspected herpes zoster and from healthy volunteers during stressful and nonstressful conditions. Methods: There were 52 patients with a diagnosis of herpes zoster (group 1), 30 with a diagnosis of zoster-mimicking disease (group 2), and 27 healthy volunteers (group 3). Saliva and plasma samples were evaluated for VZV DNA by real-time PCR analysis. Results: Among patients with suspected herpes zoster (ie, patients in groups 1 and 2), the sensitivity of PCR analysis of salivary DNA for detecting VZV (88%; 95% confidence interval [CI], 74%-95%) was significantly higher than that of PCR analysis of plasma DNA (28%; 95% CI, 16%-44%; P < .001), whereas the specificity of PCR analysis of salivary DNA (100%; 95% CI, 88%-100%) was similar to that of PCR analysis of plasma DNA (100%; 95% CI, 78%-100%; P > .99). VZV DNA was not detected in saliva and plasma samples from group 3 (0%; 95% CI, 0%-14%). Conclusions: Real-time PCR analysis of salivary DNA is more sensitive than that of plasma DNA for detecting VZV among patients with suspected herpes zoster. We found no subclinical reactivation of VZV in group 3 following exposure to common stressful conditions.
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ADN Viral/aislamiento & purificación , Herpes Zóster/diagnóstico , Herpesvirus Humano 3/aislamiento & purificación , Técnicas de Diagnóstico Molecular/métodos , Plasma/virología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Saliva/virología , Adulto , Anciano , Anciano de 80 o más Años , ADN Viral/genética , Femenino , Herpesvirus Humano 3/genética , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: Cancer is a leading cause of human death around the world and occurs through the highly complex coordination of multiple cellular pathways. Recent studies have revealed that microalgal extracts exhibit considerable pharmaceutical activities, including those against various cancer cells. Thus, microalgae are promising candidates as novel cancer therapeutic drugs. In this study, we evaluated the biological functions of the ethanolic extract of the Antarctic freshwater microalga, Bo tryidiopsidaceae sp., such as its antioxidant, anti-proliferative, apoptotic and anti-invasive properties. METHODS: To estimate antioxidant capacity of ethanol extract of Bo tryidiopsidaceae sp. (ETBO), free radical 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays were used. The anti-proliferative activity of ETBO was assessed in several cancer cell lines (A375, Hs578T and HeLa) and non-tumorigenic keratinocyte cells (HaCaT), using MTT assay. In addition, Annexin V binding was performed to detect ETBO-induced apoptotic cells, and the expression levels of apoptosis-regulating proteins, caspase-3, p53, and Bcl-2, were determined by western blot. Boyden chamber assays were used to determine anti-migratory and anti-invasive properties of ETBO. RESULTS: ETBO exhibited antioxidant activity and concentration-dependent anticancer activities, such as anti-proliferation and pro-apoptotic activities against cancer cells. Furthermore, the expression of the apoptosis-inducing proteins, p53 and caspase-3, significantly increased in response to ETBO, whereas the expression of the anti-apoptotic protein, Bcl-2, decreased. These data imply that ETBO induces apoptosis by caspase activation through the modulation of pro-apoptotic and anti-apoptotic gene, p53 and Bcl-2, respectively. In addition, ETBO significantly inhibited migration and invasion of cervical cancer cells in a concentration-dependent manner. CONCLUSION: In this study, ETBO exhibited considerable anticancer activities, such as inhibition of proliferation, invasion, and migration, as well as induction of apoptosis. These data suggest that ETBO is a promising therapeutic agent in cancer therapy and drug discovery.