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1.
Chem Soc Rev ; 53(9): 4674-4706, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38529583

RESUMO

High power conversion efficiency (PCE) and long-term stability are essential prerequisites for the commercialization of polymer solar cells (PSCs). Small-molecule acceptors (SMAs) are core materials that have led to recent, rapid increases in the PCEs of the PSCs. However, a critical limitation of the resulting PSCs is their poor long-term stability. Blend morphology degradation from rapid diffusion of SMAs with low glass transition temperatures (Tgs) is considered the main cause of the poor long-term stability of the PSCs. The recent emergence of oligomerized SMAs (OSMAs), composed of two or more repeating SMA units (i.e., dimerized and trimerized SMAs), has shown great promise in overcoming these challenges. This innovation in material design has enabled OSMA-based PSCs to reach impressive PCEs near 19% and exceptional long-term stability. In this review, we summarize the evolution of OSMAs, including their research background and recent progress in molecular design. In particular, we discuss the mechanisms for high PCE and stability of OSMA-based PSCs and suggest useful design guidelines for high-performance OSMAs. Furthermore, we reflect on the existing hurdles and future directions for OSMA materials towards achieving commercially viable PSCs with high PCEs and operational stabilities.

2.
Macromol Rapid Commun ; 43(19): e2200279, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35526090

RESUMO

Organic indoor photovoltaics (IPVs) are attractive energy harvesting devices for low-power consumption electronic devices and the Internet of Things (IoTs) owing to their properties such as being lightweight, semitransparent, having multicoloring capability, and flexibility. It is important to match the absorption range of photoactive materials with the emission spectra of indoor light sources that have a visible range of 400-700 nm for IPVs to provide sustainable, high-power density. To this end, benzo[1,2-b:4,5-b']dithiophene-based homopolymer (PBDTT) is synthesized as a polymer donor, which is a classical material that has a wide bandgap with a deep highest occupied molecular orbitals (HOMO) level, and a series of random copolymers by incorporating thieno[3,4-c]pyrrole-4,6,-dione (TPD) as a weak electron acceptor unit in PBDTT. The composition of the TPD unit is varied to fine tune the absorption range of the polymers; the polymer containing 70% TPD (B30T70) perfectly covers the entire range of indoor lamps such as light-emitting diodes (LEDs) and fluorescent lamp (FL). Consequently, B30T70 shows a dramatic enhancement of the power conversion efficiency (PCE) from 1-sun (PCE: 6.0%) to the indoor environment (PCE: 18.3%) when fabricating organic IPVs by blending with PC71 BM. The simple, easy molecular design guidelines are suggested to develop photoactive materials for efficient organic IPVs.

3.
Proc Natl Acad Sci U S A ; 116(25): 12516-12523, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31164420

RESUMO

BACE1 is the rate-limiting enzyme for amyloid-ß peptides (Aß) generation, a key event in the pathogenesis of Alzheimer's disease (AD). By an unknown mechanism, levels of BACE1 and a BACE1 mRNA-stabilizing antisense RNA (BACE1-AS) are elevated in the brains of AD patients, implicating that dysregulation of BACE1 expression plays an important role in AD pathogenesis. We found that nuclear factor erythroid-derived 2-related factor 2 (NRF2/NFE2L2) represses the expression of BACE1 and BACE1-AS through binding to antioxidant response elements (AREs) in their promoters of mouse and human. NRF2-mediated inhibition of BACE1 and BACE1-AS expression is independent of redox regulation. NRF2 activation decreases production of BACE1 and BACE1-AS transcripts and Aß production and ameliorates cognitive deficits in animal models of AD. Depletion of NRF2 increases BACE1 and BACE1-AS expression and Aß production and worsens cognitive deficits. Our findings suggest that activation of NRF2 can prevent a key early pathogenic process in AD.


Assuntos
Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Transtornos Cognitivos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Ácido Aspártico Endopeptidases/genética , Transtornos Cognitivos/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Isotiocianatos/farmacologia , Camundongos , Camundongos Transgênicos , Fator 2 Relacionado a NF-E2/biossíntese , Regiões Promotoras Genéticas , Ligação Proteica , Espécies Reativas de Oxigênio/metabolismo , Sulfóxidos , Transcrição Gênica
4.
J Korean Med Sci ; 37(2): e18, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35014229

RESUMO

BACKGROUND: To determine the risk of pregnancy complications and adverse offspring outcomes in Korean women with rheumatic diseases (RDs). METHODS: Women aged 20-44 years with pregnancies ending in delivery were identified from the National Health Insurance Service-National Health Information Database (2009-2016). Women with RD including systemic lupus erythematosus (SLE), seropositive rheumatoid arthritis (SPRA), and ankylosing spondylitis (AS) (n = 4,284) were age-matched with controls (n = 26,023). Outcome variables included threatened abortion (TA), preterm birth (PB), preeclampsia/eclampsia (PE/E), intrauterine growth retardation (IGR), urinary tract infection, low birth weight (LBW) offsprings, and offspring death within 1 year of birth. RESULTS: Women with RDs had increased risks for cesarean section delivery (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.4-1.6), TA (OR, 1.4; 95% CI, 1.2-1.5), PB (OR, 2.4; 95% CI, 1.9-3.2), PE/E (OR, 4.4; 95% CI, 3.3-5.9), and IGR (OR, 2.4; 95% CI, 2.0-3.1) than the controls. The risk of pregnancy complications was increased in SLE and SPRA pregnancies but not in AS pregnancies. Offsprings of women with RDs had an increased risk of LBW (OR, 4.0; 95% CI, 3.2-4.9). The offspring mortality rate within 1 year of birth was higher in women with RDs (6.2/10,000 persons) than in the controls (4.9/10,000 persons). CONCLUSION: Women with RDs are at a risk of developing pregnancy complications, and the risk of LBW offsprings and offspring death within 1 year of birth is increased in these women. Therefore, this population requires special attention during their childbearing years.


Assuntos
Complicações na Gravidez/epidemiologia , Complicações na Gravidez/etiologia , Doenças Reumáticas/complicações , Adulto , Estudos de Coortes , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Gravidez , República da Coreia , Estudos Retrospectivos , Medição de Risco , Adulto Jovem
5.
Lupus ; 30(4): 674-679, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33460342

RESUMO

BACKGROUND: Most women with systemic lupus erythematosus (SLE) are diagnosed with the disease in their reproductive years, but the incidence and prevalence of SLE among women of childbearing age have not been studied. The objective of this study was to estimate the incidence and prevalence of SLE among the Korean women of childbearing age. METHODS: Women aged 20 to 44 years with SLE were identified from National Health Insurance Service - National Health Information Database (2009-2016), which contain health information of approximately 97% of the Korean population. SLE was defined by International Classification of Diseases, 10th revision code, M32. Incidence and prevalence were calculated per 100,000 person-years and stratified by year and age. RESULTS: A total of 12,756 women with SLE were identified. The incidence of SLE from 2011 to 2016 among women in childbearing years was 8.18/100,000 person-years (95% CI 7.94-8.43), with the highest incidence in 2016 (8.56/100,000 person-years, 95% CI 7.95-9.17) and the lowest incidence in 2012 (7.85/100,000 person-years, 95% CI 7.28-8.42). The prevalence of SLE from 2009 to 2016 among women in childbearing years was 77.07/100,000 person-years (95% CI 75.76-78.39), with the highest prevalence in 2014 (79.47/100,000 person-years, 95% CI 77.64-81.30) and the lowest in 2010 (74.19/100,000 person-years, 95% CI 72.45-75.93). The peak age for SLE incidence was between 25-39 years, and lower incidence was seen in the early (20-24 years) and late (40-44 years) childbearing age periods. There was an increasing trend in prevalence according to age in women of childbearing age, with the highest prevalence occurring in the 40-44 age group. CONCLUSIONS: The risk and burden of SLE are high among women during their childbearing years. This calls for special attention to this particular population group when allocating health resources.


Assuntos
Classificação Internacional de Doenças/normas , Lúpus Eritematoso Sistêmico/epidemiologia , Medição de Risco/métodos , Adulto , Efeitos Psicossociais da Doença , Bases de Dados Factuais , Feminino , Humanos , Incidência , Lúpus Eritematoso Sistêmico/diagnóstico , Avaliação de Resultados em Cuidados de Saúde , Prevalência , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Tempo
6.
Chem Biodivers ; 18(5): e2100031, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33719132

RESUMO

Macrophages play a major role in innate immune responses by producing a variety of immune mediators and cytokines. The stimulation of macrophages by natural products may lead to an enhanced innate immune system. This study evaluated the immunostimulatory effects of a polysaccharide-rich crude fraction of Celosia cristata L. flowers (CCP) on murine macrophages. CCP treatment induced the production of inducible nitric oxide synthase, cyclooxygenase-2, and cytokines by macrophages. Mechanistically, the activation of mitogen-activated protein kinases, NF-κB and toll-like receptor 4 were found to be associated with the stimulatory functions of CCP. CCP was found to be primarily composed of galacturonic acid and glucose in addition to small amounts of arabinose and galactose. This study demonstrated that CCP may enhance the innate immune responses and potentially improve the immune functions in the body.


Assuntos
Celosia/química , Flores/química , Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Células Cultivadas , Citocinas/análise , Citocinas/imunologia , Feminino , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C3H , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Células RAW 264.7
7.
Adv Exp Med Biol ; 1155: 611-626, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468435

RESUMO

In this study, the antioxidant properties of Viviparus contectus (V. contectus) extract were evaluated for various radical scavenging activities, ferric reducing antioxidant power (FRAP), ABTS radical scavenging activity and oxygen radical absorbance capacity (ORAC). In addition, inhibition effect of the V. contectus extract against DNA scission induced by hydroxyl radical was measured. We also studied the protective effect of V. contectus extract against oxidative damage through measurements of intracellular reactive oxygen species (ROS) in Chang cells and zebrafish embryo. We found that V. contectus extract contains strong radical scavenging activities and antioxidant properties, which prevent tert-butylhydroperoxide (t-BHP)-induced oxidative stress, enhance cell viability, reduce ROS production, inhibit oxidative damage and improve mitochondrial function in Chang cells. Also, we determined that the V. contectus extract reduced ROS production mediated by t-BHP induced oxidative stress on zebrafish embryo.


Assuntos
Antioxidantes/farmacologia , Extratos Celulares/farmacologia , Gastrópodes/química , Estresse Oxidativo , Animais , Linhagem Celular , Embrião não Mamífero , Humanos , Espécies Reativas de Oxigênio/metabolismo , Peixe-Zebra , terc-Butil Hidroperóxido
8.
Adv Exp Med Biol ; 1155: 627-641, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468436

RESUMO

Atrina pectinata (A. pectinata), called pen shell, is an edible shellfish that adheres to the seabed pointed downward and has a triangular shell reaching about 40 cm in length.In this study, we examined the antioxidant effect of an A. pectinata extract exhibiting various radical scavenging activities. These scavenging activities were evaluated using electron spin resonance. Anti-oxidant activities were also determined using the ferric reducing antioxidant power (FRAP) and the ABTS radical scavenging assays. Lipid peroxidation inhibitory activity was confirmed using ferric thiocyanate and thiobarbituric acid assays. Furthermore, the protective effect of the A. pectinata extract against t-BHP-induced oxidative stress on Chang cells were evaluated using MTT assay and the measurement of reactive oxygen species (ROS). These results showed that the A. pectinata extract have strong radical scavenging activities, and exerts protective effect against oxidative stress through reducing intracellular ROS content of Chang cells.


Assuntos
Antioxidantes/farmacologia , Bivalves/química , Extratos Celulares/farmacologia , Estresse Oxidativo , Animais , Linhagem Celular , Humanos , Peroxidação de Lipídeos , Espécies Reativas de Oxigênio/metabolismo
9.
Adv Exp Med Biol ; 1155: 1001-1014, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468463

RESUMO

Batillaria multiformis (B. multiformis) belong to gastropods. They live generally in the sandpit of the lagoons and the estuaries of the intertidal zone. Most of them are distributed in Korea, Japan and China. In this study, we investigated the anti-inflammatory potential of B. multiformis water extracts (BMW). The results showed that the extracts significantly decreased the production of nitric oxide (NO) and pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in LPS-induced RAW 264.7 macrophages. In addition, the extracts suppressed the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose dependent manner. Further investigation indicated that BMW suppressed phosphorylated c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase (ERK) and p38 through the MAPK signaling pathway and influenced the NF-κB signaling pathway by suppressing the IκBα degradation in LPS-induced RAW 264.7 macrophages.


Assuntos
Anti-Inflamatórios/farmacologia , Extratos Celulares/farmacologia , Gastrópodes/química , Macrófagos/efeitos dos fármacos , NF-kappa B/metabolismo , Transdução de Sinais , Animais , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Lipopolissacarídeos , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Água
10.
Adv Exp Med Biol ; 1155: 1069-1081, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468468

RESUMO

Scallops belong to cosmopolitan family of bivalves which are found in any oceans. They are one of the most important marine fishery resources in the world. The shell, meat and pearl layer have a high utilization value and a lot of scallops are eaten as food. In this study, we established anti-inflammatory effect of Scallops water extract in lipopolysaccharide (LPS) stimulated RAW 264.7 mononuclear macrophage. Our results indicated that Scallop water extract effectively reduced the synthesis of nitric oxide (NO). In addition, Scallop water extract suppressed the reactive oxygen species (ROS) generation and the expression of IL-6 and TNF-α. Further investigation indicated that anti-inflammatory effect of Scallop water extract via suppressing downregulation of MAPK (JNK, p38 and ERK) and NF-κB signaling.


Assuntos
Anti-Inflamatórios/farmacologia , Extratos Celulares/farmacologia , Macrófagos/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Pectinidae/química , Animais , Citocinas/metabolismo , Inflamação , Lipopolissacarídeos , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo
11.
J Neurosci ; 37(20): 5099-5110, 2017 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-28432138

RESUMO

Excessive mitochondrial fission is a prominent early event and contributes to mitochondrial dysfunction, synaptic failure, and neuronal cell death in the progression of Alzheimer's disease (AD). However, it remains to be determined whether inhibition of excessive mitochondrial fission is beneficial in mammal models of AD. To determine whether dynamin-related protein 1 (Drp1), a key regulator of mitochondrial fragmentation, can be a disease-modifying therapeutic target for AD, we examined the effects of Drp1 inhibitor on mitochondrial and synaptic dysfunctions induced by oligomeric amyloid-ß (Aß) in neurons and neuropathology and cognitive functions in Aß precursor protein/presenilin 1 double-transgenic AD mice. Inhibition of Drp1 alleviates mitochondrial fragmentation, loss of mitochondrial membrane potential, reactive oxygen species production, ATP reduction, and synaptic depression in Aß-treated neurons. Furthermore, Drp1 inhibition significantly improves learning and memory and prevents mitochondrial fragmentation, lipid peroxidation, BACE1 expression, and Aß deposition in the brain in the AD model. These results provide evidence that Drp1 plays an important role in Aß-mediated and AD-related neuropathology and in cognitive decline in an AD animal model. Therefore, inhibiting excessive Drp1-mediated mitochondrial fission may be an efficient therapeutic avenue for AD.SIGNIFICANCE STATEMENT Mitochondrial fission relies on the evolutionary conserved dynamin-related protein 1 (Drp1). Drp1 activity and mitochondria fragmentation are significantly elevated in the brains of sporadic Alzheimer's disease (AD) cases. In the present study, we first demonstrated that the inhibition of Drp1 restored amyloid-ß (Aß)-mediated mitochondrial dysfunctions and synaptic depression in neurons and significantly reduced lipid peroxidation, BACE1 expression, and Aß deposition in the brain of AD mice. As a result, memory deficits in AD mice were rescued by Drp1 inhibition. These results suggest that neuropathology and combined cognitive decline can be attributed to hyperactivation of Drp1 in the pathogenesis of AD. Therefore, inhibitors of excessive mitochondrial fission, such as Drp1 inhibitors, may be a new strategy for AD.


Assuntos
Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/metabolismo , Transtornos Cognitivos/fisiopatologia , Dinaminas/metabolismo , Depressão Sináptica de Longo Prazo , Mitocôndrias/metabolismo , Neurônios/metabolismo , Doença de Alzheimer/complicações , Animais , Encéfalo/fisiopatologia , Transtornos Cognitivos/complicações , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Inibição Neural
12.
J Antimicrob Chemother ; 73(2): 503-508, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29069496

RESUMO

Objectives: Delamanid is a new anti-TB drug, but few data exist on its use outside clinical trials. The purpose of this study was to evaluate the efficacy as well as the safety and tolerability of a delamanid-containing regimen for 24 weeks in the treatment of MDR- and XDR-TB. Methods: We performed a retrospective cohort study among patients with MDR/XDR-TB who were treated with a delamanid-containing regimen in seven hospitals in South Korea. Results: A total of 32 patients with MDR-TB, of which 6 (18.8%) were XDR-TB, were included and all completed 24 weeks of delamanid treatment. Of 19 patients (59.4%) who had positive culture sputum at the initiation of delamanid treatment, the proportion of culture conversion at 8 weeks was 72.2% (13 of 18) in solid medium and 50.0% (7 of 14) in liquid medium. The proportion of culture conversion at 24 weeks was 94.4% (17 of 18) in solid medium and 92.9% (13 of 14) in liquid medium. The median time to culture conversion was 33 days (range = 5-81) using solid medium and 57 days (range = 8-96) using liquid medium. Of the 32 patients, there was no serious adverse event or death. Three patients developed a transient QTcF of > 500 ms. Conclusions: The use of delamanid combined with optimized background regimens has the potential to achieve high culture conversion rates at 24 weeks with an acceptable safety and tolerability profile in patients with MDR/XDR-TB.


Assuntos
Antituberculosos/administração & dosagem , Antituberculosos/efeitos adversos , Nitroimidazóis/administração & dosagem , Nitroimidazóis/efeitos adversos , Oxazóis/administração & dosagem , Oxazóis/efeitos adversos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas Bacteriológicas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , República da Coreia , Estudos Retrospectivos , Escarro/microbiologia , Resultado do Tratamento , Adulto Jovem
13.
BMC Med Genet ; 19(1): 164, 2018 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-30208859

RESUMO

BACKGROUND: Multicentric carpotarsal osteolysis syndrome (MCTO) is characterized by progressive destruction and disappearance of the carpal and tarsal bones associated with nephropathy. MCTO is caused by loss-of-function mutations in the MAF bZIP transcription factor B (MAFB) gene. CASE PRESENTATION: This report describes three unrelated patients with MAFB mutations, including two male and one female patient. Osteolytic lesions in the carpal and tarsal bones were detected at 2 years, 12 years, and 14 months of age, respectively. Associated proteinuria was noted at 4 years, 12 years, and 3 months of age, respectively. Kidney biopsy was performed in two of them and revealed focal segmental glomerulosclerosis (FSGS). One patient showed progression to end-stage renal disease, that is by 1 year after the detection of proteinuria. The second patient had persistent proteinuria but maintained normal renal function. In the third patient, who did not undergo a kidney biopsy, the proteinuria disappeared spontaneously. The bony lesions worsened progressively in all three patients. Mutational study of MAFB revealed three different mutations, two novel mutations [c.183C > A (p.Ser61Arg) and c.211C > G (p.Pro71Ala)] and one known mutation [c.212C > T (p.Pro71Leu)]. CONCLUSION: We report three cases with MCTO and two novel MAFB mutations. The renal phenotypes were different among the three patients, whereas progressive worsening of the bony lesions was common in all patients. We also confirmed FSGS to be an early renal pathologic finding in two cases. A diagnosis of MCTO should be considered in patients with progressive bone loss concentrated primarily in the carpal and tarsal bones and kidney involvement, such as proteinuria.


Assuntos
Glomerulosclerose Segmentar e Focal/genética , Mutação com Perda de Função , Fator de Transcrição MafB/genética , Osteólise/genética , Proteinúria/genética , Adolescente , Sequência de Bases , Ossos do Carpo/metabolismo , Ossos do Carpo/patologia , Pré-Escolar , Análise Mutacional de DNA , Progressão da Doença , Feminino , Expressão Gênica , Glomerulosclerose Segmentar e Focal/complicações , Glomerulosclerose Segmentar e Focal/metabolismo , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Rim/metabolismo , Rim/patologia , Fator de Transcrição MafB/metabolismo , Masculino , Osteólise/complicações , Osteólise/metabolismo , Osteólise/patologia , Proteinúria/complicações , Proteinúria/metabolismo , Proteinúria/patologia , Ossos do Tarso/metabolismo , Ossos do Tarso/patologia , Adulto Jovem
14.
Molecules ; 22(5)2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28441343

RESUMO

Althaea rosea (Linn.) is a medicinal plant from China and Korea that has been traditionally used to control inflammation, to stop bedwetting and as a mouthwash in cases of bleeding gums. Its flowers are employed medicinally for their emollient, demulcent and diuretic properties, which make them useful in chest complaints. Furthermore, a flower extract decoction is used to improve blood circulation, for the treatment of constipation, dysmenorrhoea, haemorrhages, etc. However, the possible mechanisms of the immune-stimulatory effect remains to be elucidated. Therefore, we investigated the role of Althaea rosea flower (ARF) extracts in the immune-stimulatory effect of macrophages and the underlying mechanisms of action. ARF water extract (ARFW) could dose-dependently increase NO production and cytokines (IL-6 and TNF-α). We also found that ARFW significantly increased the expression of iNOS and COX-2 proteins in RAW264.7 cells. Consistent with these results, MAPK protein (JNK, ERK, p38) expression levels were induced after treatment with ARFW. Additionally, ARFW showed a marked increase in the phosphorylation level of IκBα and subsequent IκBα degradation allowing NF-κB nuclear translocation. These results suggest that the immune-stimulatory effect of A. rosea flower extracts is mediated through the translocation of NF-κB p65 subunit into the nucleus from the cytoplasm and subsequent activation of pro-inflammatory cytokines (IL-6 and TNF-α) and other mediators (iNOS and COX-2), which occurs mainly through MAPK signalling pathway. Thus, we suggest that ARFW could be considered as a potential therapeutic agent useful in the development of immune-stimulatory compounds.


Assuntos
Adjuvantes Imunológicos/farmacologia , Althaea/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Avaliação Pré-Clínica de Medicamentos , Flores/química , Lipopolissacarídeos/farmacologia , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7
15.
Ann Neurol ; 77(3): 504-16, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25558977

RESUMO

OBJECTIVE: Stroke is a leading cause of mortality and disability. The peptidyl-prolyl cis/trans isomerase Pin1 regulates factors involved in cell growth. Recent evidence has shown that Pin1 plays a major role in apoptosis. However, the role of Pin1 in ischemic stroke remains to be investigated. METHODS: We used Pin1 overexpression and knockdown to manipulate Pin1 expression and explore the effects of Pin1 in cell death on ischemic stress in vitro and in a mouse stroke model. We also used Pin 1 inhibitor, γ-secretase inhibitor, Notch1 intracellular domain (NICD1)-deleted mutant cells, and Pin1 mutant cells to investigate the underlying mechanisms of Pin1-NICD1-mediated cell death. RESULTS: Our findings indicate that Pin1 facilitates NICD1 stability and its proapoptotic function following ischemic stroke. Thus, overexpression of Pin1 increased NICD1 levels and enhanced its potentiation of neuronal death in simulated ischemia. By contrast, depletion or knockout of Pin1 reduced the NICD1 level, which in turn desensitized neurons to ischemic conditions. Pin1 interacted with NICD1 and increased its stability by inhibiting FBW7-induced polyubiquitination. We also demonstrate that Pin1 and NICD1 levels increase following stroke. Pin1 heterozygous (+/-) and knockout (-/-) mice, and also wild-type mice treated with an inhibitor of Pin1, each showed reduced brain damage and improved functional outcomes in a model of focal ischemic stroke. INTERPRETATION: These results suggest that Pin1 contributes to the pathogenesis of ischemic stroke by promoting Notch signaling, and that inhibition of Pin1 is a novel approach for treating ischemic stroke.


Assuntos
Apoptose/fisiologia , Isquemia/metabolismo , Neurônios/metabolismo , Peptidilprolil Isomerase/metabolismo , Receptor Notch1/metabolismo , Acidente Vascular Cerebral/metabolismo , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/patologia , Modelos Animais de Doenças , Humanos , Isquemia/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Peptidilprolil Isomerase/antagonistas & inibidores , Peptidilprolil Isomerase/genética , Estabilidade Proteica , Estrutura Terciária de Proteína/fisiologia , Transdução de Sinais/fisiologia , Acidente Vascular Cerebral/tratamento farmacológico
16.
Rheumatol Int ; 36(2): 207-12, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26395992

RESUMO

The prevalence and clinical features of psoriatic arthritis (PsA) in psoriasis patients vary widely in different countries, and studies on Korean population are rarely reported. The aim of this study was to investigate the clinical features of PsA in a Korean population of patients with psoriasis by using psoriatic arthritis screening questionnaires. A cross-sectional observational study was conducted, and consecutive psoriatic patients were evaluated for PsA by using two kinds of psoriatic arthritis screening questionnaires: Psoriatic Arthritis Screening and Evaluation tool (PASE) and Psoriasis Epidemiology Screening Tool (PEST). Psoriatic patients with higher score in screening questionnaires were referred to rheumatologist for confirmative diagnosis of PsA. Among 196 psoriasis patients screened by PASE and PEST, total prevalence of PsA was 11.2 % (n = 22/196) with 59.1 % of the cases being newly diagnosed. Compared with patients without PsA, patients with PsA had more extensive psoriasis, higher frequency of pustular and inverse type of psoriasis, and lower frequency of plaque type of psoriasis. Spondylitis was the most common manifestation pattern, followed by polyarthritis, oligoarthritis, predominant distal interphalangeal arthritis, and arthritis mutilans. Our findings are consistent with a low prevalence of PsA among patients with psoriasis in Asia. We also confirm a spondylitis as the most common pattern of PsA in Korea. PsA screening questionnaires can be a simple and useful tool to screen PsA in patients with psoriasis.


Assuntos
Artrite Psoriásica/diagnóstico , Psoríase/diagnóstico , Espondilite/diagnóstico , Inquéritos e Questionários , Adulto , Artrite Psoriásica/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Psoríase/epidemiologia , República da Coreia/epidemiologia , Espondilite/epidemiologia
17.
J Korean Med Sci ; 29(2): 198-203, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24550645

RESUMO

We aimed to investigate differences in clinical manifestations and outcomes between adult and child patients with Henoch-Schönlein purpura (HSP), and to analyze the factors associated with poor prognosis for HSP nephritis. This retrospective 10-yr study enrolled 160 patients with HSP who visited Severance Hospital. Purpura was mostly detected in lower extremities, but purpura in upper extremities was more frequently observed in adults than children (41.7% vs 19.3%). Children had a greater frequency of arthralgia (55.4% vs 27.1%), while adults had a greater frequency of diarrhea (20% vs 1.6%). Anemia, elevated C-reactive protein, and level of IgA were more frequently observed in adults (25% vs 7.1%, 65.6% vs 38.4%, 26.3% vs 3.5%). Renal involvement in adults was more severe than in children (79.2% vs 30.4%). Chronic renal failure showed a significant difference in outcomes of HSP between adults (10.4%) and children (1.8%) after a follow up period of an average of 27 months. Furthermore, renal insufficiency at diagnosis was significantly related to the progression to chronic renal failure. Our results showed several differences in the clinical features of HSP between adults and children. Adults with HSP had a higher frequency of renal insufficiency and worse renal outcomes than children. Renal insufficiency at diagnosis might be of predictive value for the progression to chronic renal failure in HSP patients.


Assuntos
Vasculite por IgA/diagnóstico , Vasculite por IgA/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artralgia/epidemiologia , Artralgia/etiologia , Proteína C-Reativa/análise , Criança , Pré-Escolar , Diarreia/epidemiologia , Diarreia/etiologia , Extremidades/patologia , Feminino , Seguimentos , Humanos , Vasculite por IgA/complicações , Vasculite por IgA/tratamento farmacológico , Imunoglobulina A/sangue , Imunossupressores/uso terapêutico , Lactente , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Insuficiência Renal/epidemiologia , Insuficiência Renal/etiologia , Estudos Retrospectivos , Adulto Jovem
18.
Nat Commun ; 15(1): 5561, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956100

RESUMO

Structural deformation modifies the bandgap, exciton fine structure and phonon energy of semiconductors, providing an additional knob to control their optical properties. The impact can be exploited in colloidal semiconductor quantum dots (QDs), wherein structural stresses can be imposed in three dimensions while defect formation is suppressed by controlling surface growth kinetics. Yet, the control over the structural deformation of QDs free from optically active defects has not been reached. Here, we demonstrate strain-graded CdSe-ZnSe core-shell QDs with compositionally abrupt interface by the coherent pseudomorphic heteroepitaxy. Resulting QDs tolerate mutual elastic deformation of varying magnitudes at the interface with high structural fidelity, allowing for spectrally stable and pure emission of photons at accelerated rates with near unity luminescence efficiency. We capitalize on the asymmetric strain effect together with the quantum confinement effect to expand emission envelope of QDs spanning the entire visible region and exemplify their use in photonic applications.

19.
Korean J Intern Med ; 38(1): 125-133, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35581954

RESUMO

BACKGROUND/AIMS: Women with rheumatoid arthritis (RA) are often diagnosed with the disease during their reproductive years; however, its incidence and prevalence among women of childbearing age have not been studied. The objective of this study was to estimate the incidence and prevalence of seropositive rheumatoid arthritis (SPRA) among Korean women of childbearing age. METHODS: Women aged 20 to 44 years with SPRA were identified from National Health Insurance Service-National Health Information Database (2009 to 2016). SPRA was defined by International Classification of Diseases, 10th revision code, M05. Incidence and prevalence were calculated per 100,000 person-years and stratified by year and age. RESULTS: The average incidence and prevalence of SPRA from 2011 to 2016 among women of childbearing age was 24.1/100,000 person-years (95% confidence interval [CI], 23.7 to 24.5) and 105.2/100,000 person-years (95% CI, 100.9 to 109.5), respectively. The incidence increased annually from 21.0/100,000 person-years (95% CI, 20.1 to 21.9) in 2009 to 28.4 person-years (95% CI, 27.3 to 29.5) in 2016. Similarly, the prevalence increased annually from 95.7/100,000 person-years (95% CI, 93.7 to 97.6) in 2009 to 111.0 person-years (95% CI, 108.9 to 113.2) in 2015, with a slight decrease in 2016 (110.4 person-years; 95% CI, 108.2 to 112.6). The incidence and prevalence of SPRA increased with advancing age. The peak age for both incidence and prevalence of SPRA among women of childbearing age was 40 to 44 years. CONCLUSION: The risk of SPRA is high in women during their childbearing years; this population bears a significant disease burden. This calls for special attention to this particular population group to reduce the risk and burden of this disease.


Assuntos
Artrite Reumatoide , Humanos , Feminino , Prevalência , Incidência , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Bases de Dados Factuais , República da Coreia/epidemiologia
20.
ACS Appl Mater Interfaces ; 15(20): 24670-24680, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37159422

RESUMO

To realize efficient, green solvent-processable organic solar cells (OSCs), considerable effort has been expended on the development of conjugated materials with both superior optoelectrical properties and processability. However, molecular design strategies that enhance solubility often reduce crystalline/electrical properties of the materials. In this study, we develop three new guest small-molecule acceptors (SMAs) (Y-4C-4O, Y-6C-4O, and Y-12C-4O) featuring inner side chains consisting of terminal oligo(ethylene glycol) (OEG) groups and alkyl spacers of different lengths. When a host SMA (Y6) and guest SMA (Y-nC-4O) are mixed, favorable interactions between these materials lead to the formation of "alloy-like" composites. The alloy-like SMA composites enable sufficient processing in o-xylene to afford suitable blend-film morphologies. It is also found that the lengths of the alkyl spacers in guest SMAs have a significant impact on the performance of the o-xylene-processed OSCs. The PM6:Y6:Y-4C-4O blend achieves a maximum power conversion efficiency (PCE) of 17.03%, outperforming PM6:Y6:Y-6C-4O (PCE = 15.85%) and PM6:Y6:Y-12C-4O (PCE = 12.12%) OSCs. The high PCE of the PM6:Y6:Y-4C-4O device is mainly attributed to the well-intermixed morphology and superior crystalline/electrical properties, which result from the high compatibility of the Y6:Y-4C-4O composites with PM6. Thus, we demonstrate that an alloy-like SMA composite based on well-designed OEG-incorporated Y-series SMAs can afford green solvent-processable, high-performance OSCs.

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