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1.
Healthcare (Basel) ; 12(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38998773

RESUMO

This study aimed to analyze the long-term care insurance for older adults in South Korea in terms of community care. An analytical framework was designed for the study, focusing on comprehensiveness, adequacy, and integration. The findings suggest that Korean LTCI is significantly limited for the development of community care. First, in terms of comprehensiveness, the use of visiting nurses and the availability of short-stay services have been significantly reduced, and the supporting services for informal caregivers are at the beginning stage of their introduction. Second, in terms of adequacy, the quantity of benefits, such as three to four hours of care a day, are insufficient to meet older adults' substantial needs. Furthermore, the overall quality of home care services is low, particularly with regard to short-stay services and welfare equipment. Finally, in terms of integration, basic linkage of organizations has not been properly conducted in local areas, and there remains an absence of care managers in the LTCI system. To cope with these challenging issues, the following policy measures are suggested: the activation of rehabilitation services, the expansion of benefit quantities, the improvement of service quality, and the creation of organizational linkages through local authorities and long-term care centers.

2.
Biochemistry ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38252844

RESUMO

Erythropoietin-producing hepatoma (Eph) receptors are a family of tyrosine kinases that can act as tumor promoters or tumor suppressors, depending on the receptor and cancer cell type. Cancer-associated somatic mutations have been identified in all Eph receptors, but in most cases, the functional effects of the mutations are unknown. In this study, we expressed and purified the kinase domains of wild-type (WT) EphA3 and EphB2 along with 16 cancer-associated mutants. We identified mutations that decrease EphA3 activity and both activating and inhibitory mutations in EphB2. To shed light on the mechanisms by which the mutations altered kinase activity, we measured the thermal stabilities of the enzymes and performed steady-state kinetic experiments. We also expressed the full-length receptors in HEK293T cells to determine the cellular effects. WT EphB2 promoted downstream ERK signaling, while a kinase-inactive mutant (S706F) was similar to the control cells. In contrast, WT EphA3 (but not loss-of-function mutants) inhibited ERK signaling. The reciprocal effects of EphB2 and EphA3 on ERK phosphorylation in HEK293T cells were also evident in Ras-GTP loading. Thus, consistent with the dual roles of Eph receptors as tumor promoters and tumor suppressors, somatic mutations have the potential to increase or decrease Eph function, resulting in changes in the downstream signaling transduction.

3.
Healthcare (Basel) ; 11(21)2023 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-37957995

RESUMO

This study analyses old-age capital in its economic, cultural, and social components, in terms of how it impacts on depression in the elderly, comparing urban and rural regions. Our comparative analysis in urban and rural areas focuses on South Korea, using the Korean Welfare Panel Data from 2012 to 2020. Time-series trends and variables measuring capital and depression in older adults were examined in panel data analyses. Depression among the Korean elderly was at a similar level in urban and rural areas, whereas satisfaction regarding income levels, leisure life, and social relationships was higher for older adults in rural areas. We also found that the higher the economic capital, the higher the leisure life satisfaction (cultural capital), and the higher the social relationship satisfaction (social capital), the lower the rates of depression. Finally, depression among the urban elderly did not decrease as house prices increased as a component of economic capital, and depression decreased among groups participating in volunteer activities as part of the social capital of the rural elderly. In accordance with the socioemotional selectivity theory, older adults in rural areas in Korea have an advantage in terms of cultural capital due to their environment, whereas the psychosocial environment theory is relevant to urban elderly people experiencing relative deprivation in terms of economic capital.

4.
J Biol Chem ; 299(9): 105115, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37527777

RESUMO

Erythropoietin-producing hepatoma (Eph) receptor tyrosine kinases regulate the migration and adhesion of cells that are required for many developmental processes and adult tissue homeostasis. In the intestinal epithelium, Eph signaling controls the positioning of cell types along the crypt-villus axis. Eph activity can suppress the progression of colorectal cancer (CRC). The most frequently mutated Eph receptor in metastatic CRC is EphB1. However, the functional effects of EphB1 mutations are mostly unknown. We expressed and purified the kinase domains of WT and five cancer-associated mutant EphB1 and developed assays to assess the functional effects of the mutations. Using purified proteins, we determined that CRC-associated mutations reduce the activity and stability of the folded structure of EphB1. By mammalian cell expression, we determined that CRC-associated mutant EphB1 receptors inhibit signal transducer and activator of transcription 3 and extracellular signal-regulated kinases 1 and 2 signaling. In contrast to the WT, the mutant EphB1 receptors are unable to suppress the migration of human CRC cells. The CRC-associated mutations also impair cell compartmentalization in an assay in which EphB1-expressing cells are cocultured with ligand (ephrin B1)-expressing cells. These results suggest that somatic mutations impair the kinase-dependent tumor suppressor function of EphB1 in CRC.


Assuntos
Neoplasias Colorretais , Receptor EphB1 , Animais , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/fisiopatologia , Mutação , Receptor EphB1/genética , Receptor EphB1/metabolismo , Transdução de Sinais/fisiologia , Linhagem Celular , Ativação Enzimática/genética , Estabilidade Proteica , Sistema de Sinalização das MAP Quinases/genética , Movimento Celular/genética
5.
Biochemistry ; 62(6): 1124-1137, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36854171

RESUMO

Tyrosine kinases (TKs) play essential roles in signaling processes that regulate cell survival, migration, and proliferation. Dysregulation of tyrosine kinases underlies many disorders, including cancer, cardiovascular and developmental diseases, as well as pathologies of the immune system. Ack1 and Brk are nonreceptor tyrosine kinases (NRTKs) best known for their roles in cancer. Here, we have biochemically characterized novel Ack1 and Brk mutations identified in patients with systemic lupus erythematosus (SLE). These mutations are the first SLE-linked polymorphisms found among NRTKs. We show that two of the mutants are catalytically inactive, while the other three have reduced activity. To understand the structural changes associated with the loss-of-function phenotype, we solved the crystal structure of one of the Ack1 kinase mutants, K161Q. Furthermore, two of the mutated residues (Ack1 A156 and K161) critical for catalytic activity are highly conserved among other TKs, and their substitution in other members of the kinase family could have implications in cancer. In contrast to canonical gain-of-function mutations in TKs observed in many cancers, we report loss-of-function mutations in Ack1 and Brk, highlighting the complexity of TK involvement in human diseases.


Assuntos
Neoplasias , Humanos , Mutação , Fosforilação , Tirosina
6.
J Prev Med Public Health ; 56(1): 88-94, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36746426

RESUMO

OBJECTIVES: This study examined how deprivation differed by region and the effect those differences had on suicidal ideation among the local population. METHODS: Data collected over 10 years (2012-2021) in the Korea Welfare Panel Study were organized into 3 categories: metropolitan, city, and rural. A panel analysis was conducted on the impact of deprivation indices, socio-demographic characteristics, and life satisfaction on suicidal ideation in each category. RESULTS: Income, divorce status, family relationship satisfaction, and medical deprivation had a significant impact on suicidal ideation in metropolitan areas, whereas these variables did not have significant effects in rural areas. In other words, income, family, and medical support were more impactful in city areas. CONCLUSIONS: Although the deprivation index was higher in rural areas than in city areas due to an aging population and reduced income levels, the mental health of rural residents was found to be generally better than that of city residents. The possibility that this is related to the strength of relationships within the respective communities should be considered in light of recent discussions on relational welfare.


Assuntos
Renda , Ideação Suicida , Humanos , Idoso , Saúde Mental , República da Coreia/epidemiologia , Fatores de Risco
7.
Healthcare (Basel) ; 11(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36673574

RESUMO

This study aims to examine the characteristics of long-term care (LTC) financing in Organization for Economic Cooperation Development (OECD) countries. To this end, the 26 OECD countries that have introduced LTC systems were classified into three types of models: tax-based, health insurance, and LTC insurance (LTCI) systems. Thereafter, these systems were analyzed using Gilbert and Terrell's policy analysis framework. The results indicated differences in the characteristics of each type of financing in terms of allocation, benefit provision, service delivery, and finance. It is likely that while the LTC insurance model was mainly based on universalism and showed the highest level of coverage, the tax-based and health insurance models adopted selectivism with lower level of benefits per capita. In terms of service delivery, local authorities tended to have the responsibility to decide LTC service users and provide services in many countries, regardless of the type of model. In terms of finance, LTC insurance-based countries had the highest LTC expenditure as a percentage of GDP, followed by countries with tax-based and health insurance systems.

8.
J Food Sci Technol ; 59(12): 4915-4923, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36276534

RESUMO

This study aimed to investigate the effect of mixture of herbal extracts and supplementary formula (FNP-C) on hangovers and antioxidant enzymes in alcohol-induced liver damage in rats. HepG2 cells were used as the experimental cells and divided into five groups: non-treated control (normal), alcohol-induced control (control), mixture of herbal extracts (FNP-B), FNP-C, and a commercial treatment of liver diseases (Livers®); inhibition of detoxification and alcohol-induced damage was confirmed in vivo. Blood alcohol and acetaldehyde concentration after alcohol consumption were measured in a timely manner; alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), superoxide dismutase (SOD), glutathione (GSH), glutathione transferase (GST), and lactate dehydrogenase (LDH) levels were measured in the liver. FNP-C exhibited the highest effect. When FNP-C was administered to alcohol-induced animals, blood alcohol and acetaldehyde concentration decreased compared to FNP-B and Livers®. FNP-C reduced ADH levels and improved LDH, GSH, GST, and SOD levels. The FNP-C group was effective in preventing alcohol-induced hangovers and liver damage. Thus, FNP-C improves hangovers and increases antioxidant activity in an alcohol-induced model. Adding amino acids and vitamins to natural ingredients can potentially enhance the effect of improving hangovers.

9.
Healthcare (Basel) ; 10(8)2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36011205

RESUMO

This study investigated whether a person's Sasang constitution (SC) could be a risk factor for depressive symptoms. We classified the SC of 653 participants into Taeeumin (TE), Soeumin (SE), and Soyangin (SY), using the KS−15 questionnaire. We also categorized them into depressive and non-depressive symptom groups using the Center for Epidemiologic Studies Depression scale questionnaire. A t-test and chi-square test were used to compare the general characteristics of the depressive and non-depressive symptom groups. A one-way analysis of variance compared the scores of depressive symptoms according to SC, and a multiple logistic regression obtained the odds ratios (ORs); p < 0.05. The depressive symptom score for SE (13.6 ± 9.97) was significantly higher than that for SY (9.2 ± 6.51) and TE (10.8 ± 7.70; p < 0.001; SE > TE, SY, Scheffé). SE was associated with an increased prevalence of depressive symptoms compared with SY (OR: 2.315; 95% confidence interval [CI]: 1.389−3.860, p < 0.01) and TE (OR: 1.660; 95% CI: 1.076−2.561, p < 0.05), as well as an increased prevalence of depressive symptoms compared with SY (OR: 2.907; 95% CI: 1.379−6.144, p < 0.01) after adjusting for average height and distribution of living with family, medication, and drinking. This study reveals that SC, particularly SE, could be significantly associated with and be considered a risk factor for depressive symptoms.

10.
Sensors (Basel) ; 22(12)2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35746292

RESUMO

This paper addresses the problem of real-time model predictive control (MPC) in the integrated guidance and control (IGC) of missile systems. When the primal-dual interior point method (PD-IPM), which is a convex optimization method, is used as an optimization solution for the MPC, the real-time performance of PD-IPM degenerates due to the elevated computation time in checking the Karush-Kuhn-Tucker (KKT) conditions in PD-IPM. This paper proposes a graphics processing unit (GPU)-based method to parallelize and accelerate PD-IPM for real-time MPC. The real-time performance of the proposed method was tested and analyzed on a widely-used embedded system. The comparison results with the conventional PD-IPM and other methods showed that the proposed method improved the real-time performance by reducing the computation time significantly.


Assuntos
Algoritmos
11.
Artigo em Inglês | MEDLINE | ID: mdl-34444638

RESUMO

This study aimed to explore the drinking culture in Korea by sex, age, household type, occupation, and income level to identify demographic groups with prominent drinking behaviors and factors affecting their drinking. Furthermore, we evaluated recent changes, including those due to COVID-19, in drinking behavior, using data from the Korea Welfare Panel Study from 2010 to 2020. Panel analysis was performed to reveal the effects of material deprivation, depression, and sociodemographic factors on drinking behavior. We used the AUDIT 3 scale including frequency of drinking, average amount of drinking, and frequency of excessive drinking. The two characteristics of Korean drinking are consistent with the claim of the ecological system theory that humans, as social beings, drink to facilitate social communication or promote problematic drinking when social communication is difficult. Drinking among Koreans is characterized by a pattern that alternates between social drinking and problem drinking. Our study recognizes drinking as a social problem that should be managed at social as well as national levels.


Assuntos
Alcoolismo , COVID-19 , Consumo de Bebidas Alcoólicas/epidemiologia , Humanos , República da Coreia/epidemiologia , SARS-CoV-2
12.
J Food Biochem ; : e13848, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34227129

RESUMO

The aim of this study was to assess the anti-inflammatory effects of acai berries in a Caco-2 and RAW 264.7 macrophage co-culture model. The acai berry extract (ABE) was prepared using 70% ethanol, and total anthocyanin, polyphenol, and flavonoid contents in ABE were analyzed. To the antioxidant activity of ABE, we measured radical scavenging activity as well as ferric reducing antioxidant power values. Prior to inducing inflammation, Caco-2 cells were co-cultured with RAW 264.7. Inflammation was induced using lipopolysaccharides (LPS) in RAW 264.7 cells. The transepithelial electrical resistance value was significantly recovered and the mRNA level of tight junction proteins, including ZO-1, JAM-1, and claudin-4, tended to increase compared with that in the LPS group. LPS-induced interleukin (IL)-6, IL-8, and prostaglandin E2 levels reduced significantly following treatment with the highest ABE concentration. In the highest ABE concentration, the phosphorylation of p65, p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase was downregulated compared with the LPS group. The phosphorylation of extracellular signal-regulated kinase showed a decreased tendency. These results suggest that acai berry may improve gastrointestinal health. PRACTICAL APPLICATIONS: Acai berry is known to have abundant anthocyanin, which has many biological activities, including anti-inflammatory, antioxidant, antihypertensive, and anticytotoxic/cytoprotective activities. This study demonstrated the anti-inflammatory effects of acai berry extracts via TEER value, expression of tight junction protein, and production of inflammatory mediators and cytokines in the Caco-2 and RAW 264.7 co-culture model. Therefore, acai berry has the potential to prevent intestinal inflammatory diseases.

13.
Healthcare (Basel) ; 9(4)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33921442

RESUMO

This is a cross-sectional study aimed to examine whether low self-rated health (SRH) is a risk factor for depression among young males and females. Data from the SRH, quality of life (QoL) and depression questionnaires as well as general information, were collected from 512 males and females aged 20-29 years in South Korea. Chi-square test was used to analyze the distribution of depression between the high and low SRH groups. Logistic regression was used to analyze the relationship between SRH and depression after adjusting for covariates. There were 32.6% males and 30.1% females who were at risk for depression. A significant difference in the distribution of depression between the low and high SRH groups in both males and females was found. The low SRH group had a higher prevalence of depression than the high SRH group in both males and females in the crude analysis. However, when the BMI, economic status, and mental component score were adjusted, the OR of the low SRH group was still significant in males. Low SRH may be a risk factor for depression especially in males. Further studies to improve SRH by developing preventive measures against depression status while considering gender characteristics are needed.

14.
Sci Signal ; 14(664)2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402335

RESUMO

Understanding the mechanisms of the Warburg shift to aerobic glycolysis is critical to defining the metabolic basis of cancer. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an aggressive cancer characterized by biallelic inactivation of the gene encoding the Krebs cycle enzyme fumarate hydratase, an early shift to aerobic glycolysis, and rapid metastasis. We observed impairment of the mitochondrial respiratory chain in tumors from patients with HLRCC. Biochemical and transcriptomic analyses revealed that respiratory chain dysfunction in the tumors was due to loss of expression of mitochondrial DNA (mtDNA)-encoded subunits of respiratory chain complexes, caused by a marked decrease in mtDNA content and increased mtDNA mutations. We demonstrated that accumulation of fumarate in HLRCC tumors inactivated the core factors responsible for replication and proofreading of mtDNA, leading to loss of respiratory chain components, thereby promoting the shift to aerobic glycolysis and disease progression in this prototypic model of glucose-dependent human cancer.


Assuntos
Carcinoma de Células Renais/genética , Ciclo do Ácido Cítrico , Dano ao DNA , DNA Mitocondrial/metabolismo , Fumarato Hidratase/genética , Neoplasias Renais/genética , Leiomiomatose/enzimologia , Síndromes Neoplásicas Hereditárias/enzimologia , Neoplasias Cutâneas/enzimologia , Neoplasias Uterinas/enzimologia , Adulto , Idoso , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/metabolismo , Reparo do DNA , Replicação do DNA , Feminino , Fumarato Hidratase/deficiência , Perfilação da Expressão Gênica , Humanos , Neoplasias Renais/etiologia , Neoplasias Renais/metabolismo , Leiomiomatose/complicações , Masculino , Pessoa de Meia-Idade , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mutação , Síndromes Neoplásicas Hereditárias/complicações , Neoplasias Cutâneas/complicações , Neoplasias Uterinas/complicações , Adulto Jovem
15.
Healthcare (Basel) ; 8(4)2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33053870

RESUMO

This study explored reasons for turnover intention among direct care workers under the Korean long-term care insurance (LTCI) system. The author conducted semi-structured interviews with 19 care workers. The study revealed four main themes underlying the intention of care workers to change or leave their jobs. Care workers struggled with demanding working conditions, and their salaries were low. Moreover, the relationships with their directors and supervisors was not good, since some care workers felt that their directors despised them or gave them inappropriate instructions, and their supervisors did not complete administrative work fairly. Lastly, some workers' health conditions prevented them from carrying out their care work. The results have implications for working practices of care workers, prices of LTCI services, training of directors and supervisors, and coverage of occupational health and safety insurance for care workers.

16.
Healthcare (Basel) ; 8(2)2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32575373

RESUMO

The purpose of this study is to analyze the wages of South Korea's care workers as reported by the Korean national health insurance services database. We also try to identify the factors determining the wages of these 1,221,085 care workers. According to the results of the analysis, first, the wage level of care workers is fundamentally low compared to other jobs; second, the labor conditions of home care facilities (compared to those in residential care facilities) are poor, because these depend on wages, which in turn depend on the external environment, such as care institutes' management; and third, it was verified that the locations of care institutes affect the wages of care workers. As the South Korean population continues to age, the supply of high-quality care workers has important clinical implications for improving the quality of care received by the elderly. Throughout this study, it is argued that the establishment of a social service corporation has become desirable in terms of strengthening public care institutes in Korea.

17.
Food Funct ; 9(10): 5426-5435, 2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30280751

RESUMO

This study investigated the effect of microencapsulated garlic and/or tomato on endothelial dysfunction induced by the PhenFlex test (PFT) in healthy male smokers. In a randomized, double-blind, placebo-controlled crossover trial, 41 healthy male smokers were randomly assigned to one of four groups to receive the test groups (in microencapsulated garlic powder, tomato extract and a mixture thereof) or the placebo group. Proteomic biomarkers related to endothelial integrity were measured in plasma. Microencapsulated garlic, tomato extract and the mixture affected endothelial integrity biomarkers differently. Garlic consumption increased prothrombin time and decreased SAA and IL-12. Tomato extract intake increased activated partial thrombin time and decreased d-dimer, SAA, sVCAM-1, IL-13 and MCP-3 levels. Consumption of the mixture increased sE-selectin and lowered D-dimer, SAA, IL-13 and IL-10 responses after PFT challenge for 6 h. The different responses became clearer under high compliance in the dietary restriction groups. This single-intake clinical trial addressed the different responses of biomarkers related to endothelial integrity.


Assuntos
Suplementos Nutricionais/análise , Endotélio Vascular/efeitos dos fármacos , Alho/química , Extratos Vegetais/administração & dosagem , Solanum lycopersicum/química , Adulto , Biomarcadores/sangue , Quimiocina CCL7/sangue , Estudos Cross-Over , Método Duplo-Cego , Composição de Medicamentos , Endotélio Vascular/metabolismo , Humanos , Interleucina-12/sangue , Interleucina-13/sangue , Masculino , Extratos Vegetais/química , Proteômica , Fumantes , Molécula 1 de Adesão de Célula Vascular/sangue , Adulto Jovem
18.
J Int Med Res ; 46(6): 2307-2316, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29623760

RESUMO

Objective The aim of this study was to investigate the relationship between working environment and weight control efforts among obese workers in Korea. Methods This study was based on the 2011 3rd Korean Working Conditions Survey, which was conducted on workers aged 15 years or older. A sample of 484 obese workers was included in the study. Multivariable logistic regression analysis was used to investigate the relationship between working environment and weight control efforts after controlling for individual variables. Adjusted odds ratios (ORs) and 95% confidence intervals were calculated. Results Of the participants, 63.4% reported that they made efforts to control their weight. After controlling for personal factors, the OR of weight control efforts for individuals working 40-49 hours per week was 2.4 times that for individuals working 60 hours or more per week. The OR of regular employment workers was 2.2 times that of non-regular workers. Conclusion We established that working hours and employment type were significantly related to weight control efforts. Therefore, we recommend that working conditions should be considered in designing effective workplace health promotion programs.


Assuntos
Peso Corporal , Manejo da Obesidade , Obesidade/terapia , Admissão e Escalonamento de Pessoal , Local de Trabalho , Adolescente , Adulto , Emprego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/prevenção & controle , República da Coreia , Fatores de Tempo , Carga de Trabalho , Adulto Jovem
19.
J Food Sci ; 82(5): 1264-1270, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28369951

RESUMO

The beneficial effects of ginger in the management of gastrointestinal disturbances have been reported. In this study, the anti-inflammatory potential of ginger extract was assessed in a cellular model of gut inflammation. In addition, the effects of ginger extract and its major active compounds on intestinal barrier function were evaluated. The response of Caco-2 cells following exposure to a mixture of inflammatory mediators [interleukin [IL]-1ß, 25 ng/mL; lipopolysaccharides [LPS], 10 ng/mL; tumor necrosis factor [TNF]-α, 50 ng/mL; and interferon [INF]-γ, 50 ng/mL] were assessed by measuring the levels of secreted IL-6 and IL-8. In addition, the mRNA levels of cyclooxygenase-2 and inducible nitric oxide synthase were measured. Moreover, the degree of nuclear factor (NF)-κB inhibition was examined, and the intestinal barrier function was determined by measuring the transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC)-dextran transfer. It was observed that ginger extract and its constituents improved inflammatory responses by decreasing the levels of nitrite, PGE2, IL-6, and IL-8 via NF-κB inhibition. The ginger extract also increased the TEER and decreased the transfer of FITC-dextran from the apical side of the epithelium to the basolateral side. Taken together, these results show that ginger extract may be developed as a functional food for the maintenance of gastrointestinal health.


Assuntos
Anti-Inflamatórios/farmacologia , Mediadores da Inflamação/toxicidade , Inflamação/tratamento farmacológico , Zingiber officinale/química , Anti-Inflamatórios/química , Células CACO-2 , Ciclo-Oxigenase 2 , Citocinas/genética , Citocinas/metabolismo , Dextranos , Fluoresceína-5-Isotiocianato/análogos & derivados , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6 , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo
20.
Bioorg Med Chem ; 25(3): 1219-1226, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28043777

RESUMO

Previously, we have reported remarkable effect of a quercetin-glutamic acid conjugate to reverse multidrug resistance (MDR) of cancer cells to a broad spectrum of anticancer agents through inhibition of P-glycoprotein (Pgp)-mediated drug efflux. Due to the hydrolysable nature, MDR-reversal activity of the quercetin conjugate was attributed to its hydrolysis product, quercetin. However, several lines of evidence demonstrated that the intact quercetin-glutamic acid conjugate has stronger MDR-reversal activity than quercetin. In order to evaluate this hypothesis and to identify a novel scaffold for MDR-reversal agents, we prepared quercetin conjugates with a glutamic acid attached at the 7-O position via a non-hydrolysable linker. Pgp inhibition assay, Pgp ATPase assay, and MDR-reversal activity assay were performed, and the non-hydrolysable quercetin conjugates showed significantly higher activities compared with those of quercetin. Unfortunately, the quercetin conjugates were not as effective as verapamil in Pgp-inhibition and thereby reversing MDR, but it is worth to note that the structurally modified quercetin conjugates with a non-cleavable linker showed significantly improved MDR-reversal activity compared with quercetin. Taken together, the quercetin conjugates with appropriate structural modifications were shown to have a potential to serve as a scaffold for the design of novel MDR-reversal agents.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Quercetina/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ácido Glutâmico/química , Humanos , Estrutura Molecular , Quercetina/química , Relação Estrutura-Atividade
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