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1.
Psychol Health Med ; 27(5): 1107-1116, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33434078

RESUMO

Assessments of the overall health status of people living alone are important for developing health promotion programs and delivering appropriate health services. In the context of universal social health insurance system of South Korea, the relationship between failure to access health-care and self-rated health among adults living alone has given little attention. In addition, the influence of objective financial status on self-rated health in adults living alone has not explored so far. The sample of the present study comprised 4,852 adults who participated in the cross-sectional 2015 Korea National Health and Nutrition Examination Survey. The main finding was that the unmet health-care needs resulting from the inability to access health-care services during the previous 12 months was independently associated with fair or poor self-rated health, especially for women living alone. Having an income below the subsistence level was significantly associated with fair or poor self-rated health among women living alone. The findings of this study demonstrate the need for policies enabling appropriate delivery of health-care services, especially for women living alone. It is necessary to provide community-based monitoring programs related to general health for women living alone with a household income below the minimum cost-of-living.


Assuntos
Acessibilidade aos Serviços de Saúde , Ambiente Domiciliar , Adulto , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Inquéritos Nutricionais , República da Coreia/epidemiologia , Fatores Socioeconômicos
2.
Int J Mol Sci ; 22(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33947048

RESUMO

Hemistepta lyrata (Bunge) Bunge is a biennial medicinal plant possessing beneficial effects including anti-inflammation, and hemistepsin A (HsA) isolated from H. lyrata has been known as a hepatoprotective sesquiterpene lactone. In this report, we explored the cytotoxic effects of H. lyrata on hepatocellular carcinoma (HCC) cells and investigated the associated bioactive compounds and their relevant mechanisms. From the viability results of HCC cells treated with various H. lyrata extracts, HsA was identified as the major compound contributing to the H. lyrata-mediated cytotoxicity. HsA increased expression of cleaved PARP and cells with Sub-G1 phase, Annexin V binding, and TUNEL staining, which imply HsA induces apoptosis. In addition, HsA provoked oxidative stress by decreasing the reduced glutathione/oxidized glutathione ratio and accumulating reactive oxygen species and glutathione-protein adducts. Moreover, HsA inhibited the transactivation of signal transducer and activator of transcription 3 (STAT3) by its dephosphorylation at Y705 and glutathione conjugation. Stable expression of a constitutive active mutant of STAT3 prevented the reduction of cell viability by HsA. Finally, HsA enhanced the sensitivity of sorafenib-mediated cytotoxicity by exaggerating oxidative stress and Y705 dephosphorylation of STAT3. Therefore, HsA will be a promising candidate to induce apoptosis of HCC cells via downregulating STAT3 and sensitizing conventional chemotherapeutic agents.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Lactonas/farmacologia , Neoplasias Hepáticas/patologia , Proteínas de Neoplasias/biossíntese , Fator de Transcrição STAT3/biossíntese , Sesquiterpenos/farmacologia , Ativação Transcricional/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Genes Reporter , Humanos , Proteínas de Neoplasias/genética , Estresse Oxidativo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Recombinantes/metabolismo , Fator de Transcrição STAT3/genética , Sorafenibe/farmacologia
3.
Toxicol Appl Pharmacol ; 399: 115036, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32407927

RESUMO

Endoplasmic reticulum (ER) stress designates a cellular response to the accumulation of misfolded proteins, which is related to disease progression in the liver. Luteolin (3',4',5,7-tetrahydroxyflavone) is a phytochemical found frequently in medicinal herbs. Although luteolin has been reported to possess the therapeutic potential to prevent diverse stage of liver diseases, its role in hepatic ER stress has not been established. Thus, the present study aimed to determine the role of luteolin in tunicamycin (Tm)-induced ER stress, and to identify the relevant mechanisms involved in its hepatoprotective effects. In hepatocyte-derived cells and primary hepatocytes, luteolin significantly decreased Tm- or thapsigargin-mediated C/EBP homologous protein (CHOP) expression. In addition, luteolin reduced the activation of three canonical signaling pathways related to the unfolded protein response, and decreased mRNA levels of glucose-regulated protein 78, ER DNA J domain-containing protein 4, and asparagine synthetase. Luteolin also significantly upregulated sestrin 2 (SESN2), and luteolin-mediated CHOP inhibition was blocked in SESN2 (+/-) cells. Moreover, luteolin resulted in phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), as well as increased nuclear Nrf2 expression. Deletion of the antioxidant response element in the human SESN2 promoter inhibited increased luciferase activation by luteolin, suggesting that Nrf2 is a critical transcription factor for luteolin-dependent SESN2 expression. In a Tm-mediated liver injury model, luteolin decreased serum alanine aminotransferase and aspartate aminotransferase activities, prevented degenerative changes and apoptosis of hepatocytes, and inhibited CHOP and glucose-regulated protein 78 expression in hepatic tissues. Therefore, luteolin may be an effective phytochemical to manage ER stress-related liver injury.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fígado/efeitos dos fármacos , Luteolina/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Nucleares/metabolismo , Tunicamicina/farmacologia , Animais , Elementos de Resposta Antioxidante/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Células HEK293 , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fosforilação/efeitos dos fármacos , Fator de Transcrição CHOP/metabolismo , Resposta a Proteínas não Dobradas/efeitos dos fármacos
4.
J Biosoc Sci ; 52(1): 1-13, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31109384

RESUMO

Even though South Korea's universal health care system was established in 1989, many South Koreans continue to encounter obstacles in their attempts to access health care. Previous studies have not investigated the relationship between health care access and utilization and perceived health in the context of a universal health care system that implements a mandatory social health insurance policy. The objective of this study was to evaluate the influence of health care access and use of preventive health care services on self-rated health among young and middle-aged adults in Korea. The sample consisted of 1242 young adults aged 20-39 years and 2389 middle-aged adults aged 40-64 years who had participated in the cross-sectional 2015 Korea National Health and Nutrition Examination Survey. Using multiple logistic regression analysis, the association between health care access and use of preventive health care services and perceived poor health among young adults and middle-aged adults was assessed. The main finding was that a history of unmet health care requirements during the past 12 months was strongly associated with fair and poor self-rated health, especially among young adults. Additionally, middle-aged adults who had attended medical check-ups during the preceding 2 years reported poorer self-rated health. This study's findings suggest that, despite South Korea's universal public insurance system, there remains the need to improve access to health care services, especially among young adults. As a health improvement strategy, it is imperative that measures be taken to promote the availability of health care services when they are required and to solve any of the various individual accessibility problems, such as cost, particularly with young adults in mind.


Assuntos
Autoavaliação Diagnóstica , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto , Fatores Etários , Estudos Transversais , Feminino , Serviços de Saúde , Nível de Saúde , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , República da Coreia , Adulto Jovem
5.
Biochim Biophys Acta Mol Cell Res ; 1864(7): 1295-1307, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28433684

RESUMO

Endoplasmic reticulum (ER) stress is characterized by an accumulation of misfolded proteins, and ER stress reduction is essential for maintaining tissue homeostasis. However, the molecular mechanisms that protect cells from ER stress are not completely understood. The present study investigated the role of sestrin 2 (SESN2) on ER stress and sought to elucidate the mechanism responsible for the hepatoprotective effect of SESN2 in vitro and in vivo. Treatment with tunicamycin (Tm) increased SESN2 protein and mRNA levels and reporter gene activity. Activating transcription factor 6 (ATF6) bound to unfolded protein response elements of SESN2 promoter, transactivated SESN2, and increased SESN2 protein expression. In addition, dominant negative mutant of ATF6α and siRNA against ATF6α blocked the ER stress-mediated SESN2 induction, whereas chemical inhibition of PERK or IRE1 did not affect SESN2 induction by Tm. Ectopic expression of SESN2 in HepG2 cells inhibited CHOP and GRP78 expressions by Tm. Moreover, SESN2 decreased the phosphorylations of JNK and p38 and PARP cleavage, and blocked the cytotoxic effect of excessive ER stress. In a Tm-induced liver injury model, adenoviral delivery of SESN2 in mice decreased serum ALT, AST and LDH activities and the mRNA levels of CHOP and GRP78 in hepatic tissues. Moreover, SESN2 reduced numbers of degenerating hepatocytes, and inhibited caspase 3 and PARP cleavages. These results suggest ATF6 is essential for ER stress-mediated SESN2 induction, and that SESN2 acts as a feedback regulator to protect liver from excess ER stress.


Assuntos
Fator 6 Ativador da Transcrição/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Estresse do Retículo Endoplasmático , Proteínas Nucleares/metabolismo , Animais , Apoptose , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Chaperona BiP do Retículo Endoplasmático , Células HEK293 , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , MAP Quinase Quinase 4/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Endogâmicos ICR , Proteínas Nucleares/genética , Peroxidases , Tunicamicina/toxicidade , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
6.
Immunity ; 31(5): 799-810, 2009 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-19853481

RESUMO

The importance of T helper type 1 (Th1) cell immunity in host resistance to the intracellular bacterium Francisella tularensis is well established. However, the relative roles of interleukin (IL)-12-Th1 and IL-23-Th17 cell responses in immunity to F. tularensis have not been studied. The IL-23-Th17 cell pathway is critical for protective immunity against extracellular bacterial infections. In contrast, the IL-23-Th17 cell pathway is dispensable for protection against intracellular pathogens such as Mycobacteria. Here we show that the IL-23-Th17 pathway regulates the IL-12-Th1 cell pathway and was required for protective immunity against F.tularensis live vaccine strain. We show that IL-17A, but not IL-17F or IL-22, induced IL-12 production in dendritic cells and mediated Th1 responses. Furthermore, we show that IL-17A also induced IL-12 and interferon-gamma production in macrophages and mediated bacterial killing. Together, these findings illustrate a biological function for IL-17A in regulating IL-12-Th1 cell immunity and host responses to an intracellular pathogen.


Assuntos
Francisella tularensis , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Células Th1/imunologia , Tularemia/imunologia , Tularemia/prevenção & controle , Animais , Células Dendríticas/imunologia , Francisella tularensis/imunologia , Interferon gama/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais
7.
BMC Complement Altern Med ; 18(1): 20, 2018 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-29351747

RESUMO

BACKGROUND: Pelargonium sidoides (PS) and Coptis chinensis root (CR) have traditionally been used to treat various diseases, including respiratory and gastrointestinal infections, dysmenorrhea, and hepatic disorders. The present study was conducted to evaluate the anti-inflammatory effects of a combination of PS and CR in vitro and in vivo. METHODS: The in vitro effects of PS + CR on the induction of inflammation-related proteins were evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The levels of nitric oxide (NO) and of inflammatory cytokines and prostaglandin E2 (PGE2) were measured using the Griess reagent and enzyme-linked immunosorbent assay (ELISA) methods, respectively. The expression of inflammation-related proteins was confirmed by Western blot. Additionally, the effects of PS + CR on paw edema volume, skin thickness, and numbers of infiltrated inflammatory cells, mast cells, COX-2-, iNOS-, and TNF-α-immunoreactive cells in dorsum and ventrum pedis skin were evaluated in a rat model of carrageenan (CA)-induced paw edema. RESULTS: PS + CR significantly reduced production of NO, PGE2 and three pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6) and also decreased levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Treatment with PS + CR significantly reduced the protein expression levels of LPS-stimulated nuclear factor kappa B (NF-κB) and phosphorylated inhibitor of NF-κB (p-I-κBα). Additionally, PS + CR significantly inhibited the increases in paw swelling, skin thickness, infiltrated inflammatory cells, mast cell degranulation, COX-2-, iNOS-, and TNF-α-immunoreactive cells in the rat model of CA-induced acute edematous paw. CONCLUSIONS: These results demonstrate that PS + CR exhibits anti-inflammatory properties through decreasing the production of pro-inflammatory mediators (NO, PGE2, TNF-α, IL-1ß, and IL-6), suppressing NF-κB signaling in LPS-induced RAW 264.7 cells. Additionally, the results of the CA-induced rat paw edema assay revealed an anti-edema effect of PS + CR. Furthermore, it is suggested that PS + CR also inhibits acute edematous inflammation by suppressing mast cell degranulation and inflammatory mediators (COX-2, iNOS, and TNF-α). Thus, PS + CR may be a potential candidate for the treatment of various inflammatory diseases, and it may also contribute to a better understanding of the molecular mechanisms underlying inflammatory response regulation.


Assuntos
Coptis/química , Inflamação/metabolismo , NF-kappa B/metabolismo , Pelargonium/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Animais , Citocinas/metabolismo , Edema/metabolismo , Expressão Gênica/efeitos dos fármacos , Masculino , Mastócitos/efeitos dos fármacos , Camundongos , Óxido Nítrico/metabolismo , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos
8.
BMC Complement Altern Med ; 17(1): 46, 2017 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-28086859

RESUMO

BACKGROUND: Cheongsangbangpung-tang (CBT) is a traditional herbal formula used in Eastern Asia to treat heat-related diseases and swellings in the skin. The present study was conducted to evaluate the anti-inflammatory effects of cheongsangbangpung-tang extract (CBTE) both in vitro and in vivo. METHODS: The in vitro effects of CBTE on the lipopolysaccharide (LPS)-induced production of inflammation-related proteins were examined in RAW 264.7 cells. The levels of nitric oxide (NO) were measured with the Griess reagent. Inflammatory cytokines and prostaglandin E2 (PGE2) were detected using the enzyme-linked immunosorbent assay (ELISA) method. Inflammation-related proteins were detected by Western blot. The effect of CBTE on acute inflammation in vivo was evaluated using carrageenan (CA)-induced paw oedema. To evaluate the anti-inflammatory effect, paw oedema volume, thickness of the dorsum and ventrum pedis skin, number of infiltrated inflammatory cells, and number of COX-2-, iNOS-immunoreactive cells were measured. RESULTS: In an in vitro study, CBTE inhibited the production of NO and PGE2 and also decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) activity, interleukin (IL)-1ß, IL-6 and tumuor necrosis factor-α. In LPS-activated macrophages, nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) signalling is a pivotal pathway in the inflammatory process. These plausible molecular mechanisms increased the phosphorylation of I-κBα, while the activation of NF-κB and the phosphorylation of MAPK by LPS were blocked by CBTE treatment. In our in vivo study, a CA-induced acute oedematous paw inflammation rat model was used to evaluate the anti-inflammatory effect of CBTE. CBTE significantly reduced the increases in paw swelling, skin thicknesses, infiltrated inflammatory cells and iNOS-, COX-2 positive cells induced by CA injection. CONCLUSIONS: Based on these results, CBTE should favourably inhibit the acute inflammatory response through modulation of NF-κB activation and MAPK phosphorylation. Furthermore, the inhibition of CBTE in rat paw oedema induced by CA is considered to be clear evidence that CBTE may be a useful source to treat inflammation.


Assuntos
Anti-Inflamatórios/administração & dosagem , Edema/tratamento farmacológico , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/imunologia , Extratos Vegetais/administração & dosagem , Animais , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Edema/genética , Edema/imunologia , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/imunologia , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/imunologia , Fosforilação/efeitos dos fármacos , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley
9.
Apoptosis ; 21(5): 642-56, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27015669

RESUMO

Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) has many pharmacological activities including anti-inflammation, anti-oxidant and anti-cancer effects. Autophagy is the basic cellular machinery involving the digestion of damaged cellular components. In the present study, we investigated the protection effects of eupatilin against arachidonic acid (AA) and iron-induced oxidative stress in HepG2 cells and tried to elucidate the molecular mechanisms responsible. Eupatilin increased cell viability against AA + iron in a concentration-dependent manner and prevented mitochondrial dysfunction and reactive oxygen species (ROS) production. In addition, AA + iron increased the levels of pro-apoptotic proteins and these changes were prevented by eupatilin. Eupatilin also induced autophagy, as evidenced by the accumulation of microtubule-associated protein 1 light chain3-II and the detection of autophagic vacuoles. Furthermore, the protective effects of eupatilin on mitochondrial dysfunction and ROS production were significantly abolished by autophagy inhibitors. Eupatilin also increased the mRNA level of sestrin-2 and its promoter-driven reporter gene activity, which resulted in the up-regulation of sestrin-2 protein. Finally, gene silencing using sestrin-2 siRNA and the ectopic expression of recombinant adenoviral sestrin-2 indicated that sestrin-2 induction by eupatilin was required for autophagy-mediated cytoprotection against AA + iron. Our results suggest that eupatilin activates sestrin-2-dependent autophagy, thereby preventing oxidative stress induced by AA + iron.


Assuntos
Autofagia , Flavonoides/farmacologia , Hepatócitos/efeitos dos fármacos , Proteínas Nucleares/metabolismo , Estresse Oxidativo , Animais , Apoptose/efeitos dos fármacos , Ácido Araquidônico/toxicidade , Linhagem Celular , Células Hep G2 , Hepatócitos/metabolismo , Hepatócitos/fisiologia , Humanos , Ferro/toxicidade , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/fisiologia , Proteínas Nucleares/biossíntese , Ratos , Espécies Reativas de Oxigênio/metabolismo
10.
Eur J Nutr ; 55(8): 2431-2444, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26593436

RESUMO

PURPOSE: Liver is the major site of biotransformation for exogenous toxins, in having a defense system against oxidative stress as well as cytochrome P450 system. Isoliquiritigenin (isoLQ) is an active component present in Glycyrrhizae radix and has been shown to have various biological activities. This study investigated the effect of isoLQ as a liver protectant against oxidative stress, both in vivo and in vitro, and also its molecular mechanisms. METHODS: We used tert-butylhydroperoxide-induced hepatocyte damage model and cadmium (Cd)-stimulated liver toxicity animal model, which are assessed by immunoblot and flow cytometry as well as plasma and histopathological parameters. RESULTS: In HepG2 cells, pretreatment of 10 and 30 µM isoLQ significantly inhibited the induction of apoptosis and mitochondrial damage, and production of reactive oxygen species. Moreover, isoLQ induced the activation of nuclear factor erythroid 2-related factor-2 (Nrf2), as indicated by an increase in its nuclear translocation and antioxidant response element-luciferase activity. IsoLQ also induced the expression of Nrf2 target phase II enzymes, such as heme oxygenase-1, glutamate-cysteine ligase catalytic subunit and NAD(P)H:quinone oxidoreductase 1. IsoLQ also induced phosphorylation of extracellular stimuli-regulated kinase (ERK), and its activation of Nrf2 was mediated with ERK-dependent phosphorylation of Nrf2, as determined by its chemical inhibitor. In rats, oral treatment of 5 and 20 mg/kg isoLQ prevented Cd-induced acute hepatic damage, as assessed by plasma parameters and semiquantative histology, such as the modified HAI grading scores and the degenerative regions in hepatic parenchyma. CONCLUSION: These findings are considered as scientific evidence that isoLQ in licorice has the function of being a hepatic protectant against oxidative damages through ERK-mediated Nrf2 activation.


Assuntos
Chalconas/farmacologia , Glycyrrhiza/química , Fígado/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Substâncias Protetoras/farmacologia , Animais , Elementos de Resposta Antioxidante/genética , Apoptose/efeitos dos fármacos , Biomarcadores/sangue , Cádmio/toxicidade , Regulação da Expressão Gênica , Glutamato-Cisteína Ligase/genética , Glutamato-Cisteína Ligase/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Fígado/metabolismo , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Substâncias Reativas com Ácido Tiobarbitúrico/análise
11.
Biol Pharm Bull ; 38(2): 184-92, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25747977

RESUMO

Although the cholinesterase inhibitor tacrine has been successfully used for the treatment of Alzheimer's disease, it is known to have hepatotoxic effects. Liquiritigenin (LQ), an active flavonoid in Glycyrrhizae radix, exerts protective effects against liver damage. This study investigated the toxic effect of tacrine on hepatocytes and the beneficial effect of LQ on tacrine intoxication in vivo and in vitro, and the underlying mechanism involved. In hepatocyte cell lines, tacrine induced cell death and oxidative stress, as indicated by decreases in cell viability and glutathione (GSH) contents, which were blocked by pretreatment with LQ. Fluorescent activated cell sorter (FACS) analysis revealed that LQ inhibited cellular H2O2 production and mitochondrial dysfunction induced by tacrine in HepG2 cells. Furthermore, LQ promoted inhibitory phosphorylation of glycogen synthase kinase-3ß (GSK3ß) and prevented decreases in GSK3ß phosphorylation induced by tacrine. In rats treatment with tacrine at 30 mg/kg increased hepatic damage as assessed by blood biochemistry and histopathology. Administration of LQ (10 or 30 mg/kg/d, per os (p.o.)) or the hepatoprotective drug sylimarin (100 mg/kg/d) for 3 d inhibited elevations in alanine aminotransferase, aspartate aminotransferase, and histological changes induced by tacrine. These results show that LQ efficaciously protects the rat liver against tacrine-induced liver damage, and suggest that LQ is a therapeutic candidate for ameliorating the hepatotoxic effects of tacrine.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Inibidores da Colinesterase/toxicidade , Flavanonas/uso terapêutico , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Substâncias Protetoras/uso terapêutico , Tacrina/toxicidade , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Flavanonas/farmacologia , Glutationa/metabolismo , Glicogênio Sintase Quinase 3 beta , Células Hep G2 , Humanos , Peróxido de Hidrogênio/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley
12.
J Ment Health ; 23(2): 94-8, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24689664

RESUMO

BACKGROUND: The upward Korean suicide trend of recent years is mainly explained by a strong rise in suicide by older people. AIMS: This study investigates the influence of physical and mental health factors on suicidal ideation among elderly people, who are either living alone or living with others. METHODS: Cross-sectional data of 1743 older adults (≥ 65 years) who completed the 2009 Korea National Health and Nutrition Examination Survey were analysed. RESULTS: The outstanding finding was that suffering a stroke was significantly associated with suicidal ideation among elderly people. A limitation in daily activities, experience of depressed feelings and high levels of stress were significantly associated with suicidal thoughts in both elderly people living alone and those living with others. CONCLUSIONS: The findings highlight the need for suicide-intervention services, which particularly target high-risk elderly people. Primary care should be provided to elderly people after suffering a stroke and/or experiencing a limitation in daily activities.


Assuntos
Nível de Saúde , Ideação Suicida , Idoso , Povo Asiático , Feminino , Humanos , Masculino , Prevalência , República da Coreia , Características de Residência
13.
Int J Nanomedicine ; 19: 2675-2690, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505168

RESUMO

Purpose: 5-fluorouracil (5-FU) is a first-line chemotherapeutic agent used to treat colorectal cancer (CRC). However, 5-FU induces drug resistance and activation of cancer stem cells (CSCs). In the present study, we designed a novel biocompatible nanomedicine system with high efficacy and biocompatibility by synthesizing mesoporous silica nanoparticle (MSN)-structured ZnO and gold ions. Oleuropein (OLP) is a phenolic compound derived from olive leaves that exerts anti-cancer effects. Therefore, we synthesized OLP-loaded ZnO/Au MSNs (ZnO/Au/OLP MSNs) and examined their anti-cancer effects on 5-FU-resistant CRC cells. Methods: ZnO/Au MSNs were synthesized and functionalized, and their physical and chemical compositions were characterized using UV-visible spectroscopy, dynamic light scattering, and transmission electron microscopy (TEM). Their effects were assessed in terms of cellular proliferation capacity, migration and invasion ability, colony-forming ability, spheroid-forming ability, reactive oxygen species (ROS) production, and mitochondrial membrane depolarization. Results: ZnO/Au MSNs were mostly composed of various ions containing ZnO and gold ions, had a spheroid phenotype, and exhibited no cytotoxicity. ZnO/Au/OLP MSNs reduced cell viability and CSC formation and induced apoptosis of 5-FU-resistant CRC cells via necrosis via ROS accumulation and DNA fragmentation. Conclusion: ZnO/Au/OLP MSNs exhibited anti-cancer activity by upregulating necrosis. These results revealed that ZnO/Au/OLP MSNs are a novel drug delivery system for 5-FU CRC therapy.


Assuntos
Neoplasias Colorretais , Glucosídeos Iridoides , Nanopartículas , Óxido de Zinco , Humanos , Dióxido de Silício/química , Espécies Reativas de Oxigênio , Nanopartículas/química , Fluoruracila/farmacologia , Necrose , Ouro/química , Íons , Neoplasias Colorretais/tratamento farmacológico , Porosidade
14.
Drug Des Devel Ther ; 18: 549-566, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38419811

RESUMO

Introduction: Tacrine, an FDA-approved acetylcholinesterase inhibitor, has shown efficacy in treating Alzheimer's disease, but its clinical use is limited by hepatotoxicity. This study investigates the protective effects of red ginseng against tacrine-induced hepatotoxicity, focusing on oxidative stress. Methods: A network depicting the interaction between compounds and targets was constructed for RG. Effect of RG was determined by MTT and FACS analysis with cells stained by rhodamine 123. Proteins were extracted and subjected to immunoblotting for apoptosis-related proteins. Results: The outcomes of the network analysis revealed a significant association, with 20 out of 82 identified primary RG targets aligning with those involved in oxidative liver damage including notable interactions within the AMPK pathway. in vitro experiments showed that RG, particularly at 1000µg/mL, mitigated tacrine-induced apoptosis and mitochondrial damage, while activating the LKB1-mediated AMPK pathway and Hippo-Yap signaling. In mice, RG also protected the liver injury induced by tacrine, as similar protective effects to silymarin, a well-known drug for liver toxicity protection. Discussion: Our study reveals the potential of RG in mitigating tacrine-induced hepatotoxicity, suggesting the administration of natural products like RG to reduce toxicity in Alzheimer's disease treatment.


Assuntos
Doença de Alzheimer , Doença Hepática Induzida por Substâncias e Drogas , Panax , Camundongos , Animais , Tacrina/farmacologia , Tacrina/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Acetilcolinesterase/metabolismo , Farmacologia em Rede , Proteínas Quinases Ativadas por AMP , Inibidores da Colinesterase/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle
15.
Antioxidants (Basel) ; 10(10)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34679678

RESUMO

Ferroptosis is a type of programmed necrosis triggered by iron-dependent lipid peroxidation. We investigated the role of B-cell translocation gene 1 (BTG1) in cystine and methionine deficiency (CST/Met (-))-mediated cell death. CST/Met (-) depleted reduced and oxidized glutathione in hepatocyte-derived cells, increased prostaglandin-endoperoxide synthase 2 expression, and promoted reactive oxygen species accumulation and lipid peroxidation, as well as necrotic cell death. CST/Met (-)-mediated cell death and lipid peroxidation was specifically inhibited by pretreatment with ferroptosis inhibitors. In parallel with cell death, CST/Met (-) blocked global protein translation and increased the expression of genes associated with the integrated stress response. Moreover, CST/Met (-) significantly induced BTG1 expression. Using a BTG1 promoter-harboring reporter gene and siRNA, activating transcription factor 4 (ATF4) was identified as an essential transcription factor for CST/Met (-)-mediated BTG1 induction. Although knockout of BTG1 in human HAP1 cells did not affect the accumulation of reactive oxygen species induced by CST/Met (-), BTG1 knockout significantly decreased the induction of genes associated with the integrated stress response, and reduced lipid peroxidation and cell death in response to CST/Met (-). The results demonstrate that CST/Met (-) induces ferroptosis by activating ATF4-dependent BTG1 induction.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33868441

RESUMO

Porphyra tenera (laver) has long been a popular and traditional seaweed food in Korea, Japan, and China. Historically, it was known as a marine medicinal herb to treat hemorrhoids and cholera morbus in Donguibogam. We investigated the effects of P. tenera extract (PTE) for its antioxidant and anti-inflammatory activities. These activities were measured using assays for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging and its superoxide dismutase- (SOD-) like activity, and through the inhibitory production of inflammatory mediators (prostaglandin E2 (PGE2), NO, tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6)) in lipopolysaccharide- (LPS-) stimulated Raw 264.7 cells. The antioxidant assay results showed that PTE displayed DPPH radical scavenging activity (46.44%), NO radical scavenging activity (67.14%), and SOD-like activity (80.29%) at a concentration of 5 mg/mL. In the anti-inflammatory assays, treatment with PTE (1 mg/mL) significantly inhibited expression levels of LPS-induced COX-2 and iNOS, as well as the production of PGE2, NO, TNF-α, and IL-6. These results show that PTE has antioxidant and anti-inflammatory properties and provide scientific evidence to explain the antioxidative and anti-inflammatory properties of PTE.

17.
J Biosoc Sci ; 42(3): 409-24, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20078902

RESUMO

This study investigated gender difference in the effects of social support, including emotional support and instrumental support (such as help when sick and financial assistance), and social activities on perceived health of middle-aged and older adults in South Korea. Data were acquired from 3771 men and 4954 women aged 40 years and older who participated in the 2005 cross-sectional survey of the Seoul Citizens Health and Social Indicators Survey. Using multiple regression analysis, both age- and gender-specific differences related to social support and engagement in social activities and self-rated poor health were examined. Poor emotional support from close friends, relatives or someone with whom one could talk about worries was strongly associated with poor self-rated health in men, with the greatest effect in older men. Lack of engagement in social activities was associated with self-rated poor health in older adults, especially in older men. Poor instrumental support was associated with perceived poor health only in middle-aged women. As a health improvement strategy for men aged 65 years and older especially, emotional support should be considered. Measures should be considered for encouraging social activities by older adults, particularly older men.


Assuntos
Promoção da Saúde , Apoio Social , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Fatores Sexuais
18.
J Biosoc Sci ; 42(1): 99-111, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19703332

RESUMO

Over the past century, the population of Korea has aged rapidly as a result of decreasing fertility and mortality. Furthermore, the percentage of the population aged 65 and older is expected to double from 7% to 14% within 18 years, a much shorter doubling period than in most other developed countries. As Korean society ages, interest in healthy and successful ageing has increased. However, although previous studies have examined various determinants of successful ageing, such as socioeconomic status, gender differences have been neglected. This study investigated gender differences as factors in successful ageing among elderly men and women. Successful ageing has been defined as having high levels of physical and social functioning. Physical functioning includes having no difficulties with activities of daily living (ADL) or instrumental activities of daily living (IADL). Social functioning is defined as participation in at least one of the following social activities: paid work, religious gatherings or volunteer service. Data for this study were obtained from a representative sample of 761 community-living individuals aged 65-84 years (340 males, 421 females); the respondents were interviewed face-to-face as part of the third wave of the Hallym Ageing Study (2007). Socioeconomic status appears to have a greater gender-specific effect on physical functioning than on social functioning. Especially for elderly men, a higher monthly individual income was significantly related to a higher level of physical functioning. Among elderly women, a higher level of education was associated with a higher level of physical functioning. In a major metropolis, elderly men had low social functioning and elderly women had low physical functioning. As Korea's population ages, successful ageing has received much attention. This study shows that policies promoting successful ageing must consider gender differences and associated socioeconomic factors.


Assuntos
Envelhecimento/etnologia , Dinâmica Populacional , Caracteres Sexuais , Atividades Cotidianas/classificação , Idoso , Idoso de 80 Anos ou mais , Comparação Transcultural , Feminino , Nível de Saúde , Humanos , Masculino , Razão de Chances , Vigilância da População , República da Coreia , Ajustamento Social , Fatores Socioeconômicos
19.
J Nanosci Nanotechnol ; 20(1): 524-529, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383204

RESUMO

Yttria-stabilized zirconia (YSZ) and Al2O3 multilayer coatings were fabricated by plasma spraying. Thermal conductivity and thermal shock test were investigated to find out the thermal properties of the coating layer and the surface of the crack. Thermal conductivity was investigated using laser flash method and thermal shock were measured by water quenching method. Furthermore, the factors influencing thermal properties of these coatings were analyzed in detail. Multilayer coatings have imperfect interfaces. At an imperfect interface, the heat transfer coefficient was close to zero, indicating a low thermal conductivity. Multilayer coatings increase thermal shock resistance. This is because ZrO2 phases transformation from tetragonal to monoclinic occurring to the cooling process, resulting in microcracks due to volume expansion. The crack generated at this time dispersed and absorbed the thermal shock, so that it exhibited excellent thermal shock resistance.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32190091

RESUMO

Pelargonium sidoides (PS) is traditionally used to treat respiratory and gastrointestinal infections, dysmenorrhea, and hepatic disorders in South Africa. Coptis Rhizoma (CR) is used to treat gastroenteric disorders, cardiovascular diseases, and cancer in East Asia. In the present study, we intended to observe the possible beneficial antiasthma effects of PS and CR on the ovalbumin- (OVA-) induced asthma C57BL/6J mice. Asthma in mice was induced by OVA sensitization and subsequent boosting. PS + CR (300 and 1,000 mg/kg; PO) or dexamethasone (IP) was administered once a day for 16 days. The changes in the body weight and gains, lung weights and gross inspections, total and differential cell counts of leukocytes in bronchoalveolar lavage fluid (BALF), serum OVA-specific immunoglobulin E (OVA-sIgE) levels, interleukin-4 (IL-4) and IL-5 levels in BALF and lung tissue homogenate, and IL-4 and IL-5 mRNA levels in lung tissue homogenates were analyzed with lung histopathology: mean alveolar surface area (ASA), alveolar septal thickness, numbers of inflammatory cells, mast cells, and eosinophils infiltrated in the alveolar regions, respectively. Significant increases in lung weights, total and differential cell counts of leukocytes in BALF, serum OVA-sIgE levels, and IL-4 and IL-5 levels in BALF and lung tissue homogenate were observed in OVA control as compared to those of intact control. In addition, OVA control showed a significant decrease in mean ASA and increases in alveolar septal thickness, numbers of inflammatory cells, mast cells, and eosinophils infiltrated in alveolar regions. However, these allergic and inflammatory asthmatic changes were significantly inhibited by PS + CR in a dose-dependent manner. In this study, PS + CR showed dose-dependent beneficial effects on OVA-induced asthma in mice through anti-inflammatory and antiallergic activities. Therefore, it is expected that PS + CR have enough potential as a new therapeutic agent or as an ingredient of a medicinal agent for various allergic and inflammatory respiratory diseases including asthma.

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