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1.
Int J Toxicol ; : 10915818241293993, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39486087

RESUMO

Nanoplastics (NPx) can enter living organisms, including humans, through ecosystems, inhalation, and dermal contact and can be found from the intestine to the brain. However, it is unclear whether NPx accumulates and affects the dopamine system. In this study, we investigated the effects of NPx on the dopamine system in cultured murine cerebral cortex neurons. Cultured cerebrocortical neurons were treated with 100 nm NPx at the following concentrations for 24 h: 1.896 × 105, 3.791 × 106, 7.583 × 107, 1.571 × 109, 3.033 × 1010, and 3.033 × 1011 particles/mL. Dopamine-associated proteins were analyzed using immunofluorescence staining. NPx treatment induced its accumulation in neurons in a dose-dependent manner and increased the levels of dopamine receptors D1 and D2 and their co-expression. However, NPx treatment did not affect the levels of other dopamine receptors, dopamine transporters, tyrosine hydroxylase, and microtubule-associated protein 2, or synaptophysin in neuronal structures. This study demonstrated that NPx is a potential modulator of the dopamine system via its receptors rather than its synthesis and reuptake in neurons and may be associated with dopamine-based psychiatric disorders.

2.
Thorax ; 78(11): 1080-1089, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37495367

RESUMO

BACKGROUND: Diet has a crucial role in the gut microbiota, and dysbiosis in the gut and lungs has been suggested to be associated with chronic obstructive pulmonary disease. We compared the diet, microbiome and metabolome between asymptomatic smokers and those with emphysema. METHODS: We enrolled 10 asymptomatic smokers with preserved lung function and 16 smokers with emphysema with severe airflow limitation. Dietary intake information was gathered by a self-reported questionnaire. Sputum and faecal samples were collected for microbial and metabolomics analysis. A murine model of emphysema was used to determine the effect of metabolite supplementation. RESULTS: Despite having a similar smoking history with emphysema patients, asymptomatic smokers had higher values of body mass index, fibre intake and faecal acetate level. Linear discriminant analysis identified 17 microbial taxonomic members that were relatively enriched in the faeces of asymptomatic smokers. Analysis of similarity results showed dissimilarity between the two groups (r=0.287, p=0.003). Higher acetate level was positively associated with forced expiratory volume in one second in the emphysema group (r=0.628, p=0.012). Asymptomatic smokers had a greater number of species associated with acetate and propionate (r>0.6) than did those with emphysema (30 vs 19). In an emphysema mouse model, supplementation of acetate and propionate reduced alveolar destruction and the production of proinflammatory cytokines, and propionate decreased the CD3+CD4+IL-17+ T-cell population in the lung and spleen. CONCLUSION: Smokers with emphysema showed differences in diet, microbiome and short-chain fatty acids compared with asymptomatic smokers. Acetate and propionate showed therapeutic effects in a smoking-induced murine model of emphysema.


Assuntos
Enfisema , Microbioma Gastrointestinal , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Humanos , Animais , Camundongos , Fumantes , Propionatos , Modelos Animais de Doenças , Volume Expiratório Forçado , Enfisema/complicações , Acetatos
3.
Eur J Clin Pharmacol ; 79(1): 39-61, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36334108

RESUMO

PURPOSE: Aspirin has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between aspirin use and the risk of occurrence of hepatocellular carcinoma (HCC). The purpose of this study was to assess the effect of aspirin on clinical outcomes in patients with HCC in a meta-analysis and to explore the possible dose-response relationship. METHODS: A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined hazard ratios (HRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of aspirin on the risk of HCC. Relevant subgroup analyses and sensitivity analyses were performed. RESULTS: The results show that aspirin use correlated with lower incidence of HCC (HR: 0.75, 95% CI: 0.71-0.80), decreased risk of HCC recurrence (HR: 0.79, 95% CI: 0.65-0.96), and reduced mortality (HR: 0.72, 95% CI: 0.60-0.87). The results of the subgroup analysis showed that aspirin use was consistently associated with reduced incidence of HCC across different regions, study designs, and populations. A linear relationship was found for both dosage and duration of aspirin use. An increased of bleeding with aspirin use among patients was also observed (HR 1.10, 95% CI: 1.02-1.20). CONCLUSIONS: This meta-analysis found that aspirin use was independently associated with a reduced risk of HCC incidence, recurrence, and death. Furthermore, aspirin use influenced HCC occurrence in a dose-dependent and duration-dependent manner. However, an increased risk of bleeding with aspirin use was noted.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Aspirina/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/prevenção & controle , Incidência , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle , Modelos de Riscos Proporcionais
4.
BMC Ophthalmol ; 23(1): 482, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38001418

RESUMO

BACKGROUND: To compare the accuracy of nine intraocular lens (IOL) power calculation formulas, including three traditional formulas (SRK/T, Haigis, and Hoffer Q) and six new-generation formulas (Barrett Universal II [BUII], Hill-Radial Basis Function [RBF] 3.0, Kane, Emmetropia verifying optical [EVO], Ladas Super, and Pearl-DGS) in patients who underwent cataract surgery after acute primary angle closure (APAC). METHODS: In this retrospective cross-sectional study, 44 eyes of 44 patients (APAC) and 60 eyes of 60 patients (control) were included. We compared the mean absolute error, median absolute error (MedAE), and prediction error after surgery. Subgroup analyses were performed on whether axial length (AL) or preoperative laser peripheral iridotomy affected the postoperative refractive outcomes. RESULTS: In the APAC group, all formulas showed higher MedAE and more myopic shift than the control group (all P < 0.05). In APAC eyes with AL ≥ 22 mm, there were no differences in MedAEs according to the IOL formulas; however, in APAC eyes with AL < 22 mm, Haigis (0.49 D) showed lower MedAE than SRK/T (0.82 D) (P = 0.036) and Hill-RBF 3.0 (0.54 D) showed lower MedAE than SRK/T (0.82 D), Hoffer Q (0.75 D) or Kane (0.83 D) (P = 0.045, 0.036 and 0.027, respectively). Pearl-DGS (0.63 D) showed lower MedAE than Hoffer Q (0.75 D) and Kane (0.83 D) (P = 0.045 and 0.036, respectively). Haigis and Hill-RBF 3.0 showed the highest percentage (46.7%) of eyes with PE within ± 0.5 D in APAC eyes with AL < 22 mm. Iridectomized eyes did not show superior precision than the non-iridotomized eyes in the APAC group. CONCLUSIONS: Refractive errors in the APAC group were more myopic than those in the control group. Haigis and Hill-RBF 3.0 showed high precision in the eyes with AL < 22 mm in the APAC group.


Assuntos
Lentes Intraoculares , Miopia , Facoemulsificação , Humanos , Estudos Retrospectivos , Estudos Transversais , Refração Ocular , Miopia/cirurgia , Óptica e Fotônica , Biometria , Comprimento Axial do Olho
5.
BMC Gastroenterol ; 22(1): 121, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35287591

RESUMO

BACKGROUND: Previous studies have confirmed that systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) can predict the prognosis and chemotherapy efficacy of various malignant tumors. However, to the best of our knowledge, no study investigated the SII combined with PNI score to predict the efficacy of anti-programmed death 1 (anti-PD-1) antibody sintilimab and XELOX regimen (capecitabine plus oxaliplatin) in the treatment of locally advanced gastric cancer. This study aims to evaluate the predictive value of pre-treatment SII-PNI score on the sensitivity of sintilimab immunotherapy combined with XELOX chemotherapy in patients with locally advanced gastric cancer. METHODS: We registered a prospective clinical study involving 30 locally advanced gastric cancer patients from March 2020 to July 2021. The pre-treatment SII and PNI were calculated from peripheral blood samples, and the cut-off value was calculated by receiver operating characteristic. The SII-PNI score ranged from 0 to 2 and were categorized into the following: score of 2, high SII (≥ 568.5) and low PNI (≤ 52.7); score of 1, either high SII or low PNI; score of 0, no high SII nor low PNI. RESULTS: All patients were evaluated by RECIST1.1 criteria after four cycles of sintilimab immunotherapy combined with XELOX chemotherapy, including 5 patients with TRG 3 and 25 patients with non-TRG 3. The SII-PNI score of non-TRG 3 patients was significantly lower than that of TRG 3 patients (P = 0.017). The medial progression free survival of patients with low SII-PNI score was significantly better than that of patients with high SII-PNI score (P < 0.001). Multivariate analysis showed that SII-PNI score was an independent prognostic factor for predicting progression-free survival (P = 0.003). CONCLUSION: The pre-treatment SII-PNI score is a significant indicator for predicting chemosensitivity of locally advanced patients after sintilimab immunotherapy combined with XELOX chemotherapy, which can help to identify high-risk groups and predict prognosis. TRIAL REGISTRATION: The registered name of the trial is "Prospective clinical study of sintilimab combined with chemotherapy for neoadjuvant therapy in locally advanced gastric cancer". Its Current Controlled Trials number is ChiCTR2000030414. Its date of registration is 01/03/2020.


Assuntos
Terapia Neoadjuvante , Neoplasias Gástricas , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina/uso terapêutico , Humanos , Imunoterapia , Avaliação Nutricional , Oxaloacetatos , Prognóstico , Receptor de Morte Celular Programada 1 , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico
6.
Postgrad Med J ; 98(1165): 866-870, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37063031

RESUMO

OBJECTIVES: Studies on the association between metformin use and the risk of oesophageal cancer (OC) have generated controversial findings. This updated meta-analysis was conducted to reassess the effects of metformin on OC. METHODS: A comprehensive search strategy was conducted to select relevant studies from origination to February 2021. Heterogeneity was evaluated through the Q test and I2 statistics. HRs and 95% CIs were pooled through either random-effect or fixed-effect models. Meta-regression, subgroup analyses, sensitivity analysis and publication bias diagnosis were also performed. RESULTS: Seven studies with 5 426 343 subjects were included. Metformin use was associated with reduced risk of OC (HR=0.69, 95% CI 0.54 to 0.87, p<0.001). Sensitivity analysis suggested that the results were relatively stable. CONCLUSION: Metformin is associated with a reduced risk of OC. More well-designed studies are still needed to further elaborate on these associations. PROSPERO REGISTRATION NUMBER: CRD42021237127.


Assuntos
Neoplasias Esofágicas , Metformina , Humanos , Metformina/uso terapêutico , Neoplasias Esofágicas/prevenção & controle
7.
Int J Environ Health Res ; 32(1): 131-140, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32191530

RESUMO

The toxicity of cadmium (Cd) occurs through accumulation in the environment. The precise mechanism underlying Cd toxicity remains unclear. Therefore, in the present study, we studied the effects of Cd on MM55.K cells and investigated the mechanisms underlying Cd-induced cell death. CdCl2 significantly elevated apoptotic cell death, mitochondrial membrane potential (ΔΨm) loss, and caspase-dependent cell death. Moreover, immunoblotting results revealed that CdCl2 down-regulated the inhibitor of apoptotic protein such as survivin and Bcl-2 which led to the activation of caspase-3 and the cleavage of PARP in MM55.K cells. Besides, CdCl2 caused the up-regulation of ROS-related proteins such as HO-1 and ER stress-related proteins such as GRP78 and CHOP in MM55.K cells. CdCl2 toxicity resulted in the down-regulation of the AKT pathway that leads to the up-regulation of phosphorylated JNK and p38 in MM55.K cells. Thus, CdCl2 induce toxicity by AKT/MAPK regulation and causing ROS production, ER stress, ΔΨm loss, and apoptotic cell death in normal mouse renal cells.


Assuntos
Cádmio , Mitocôndrias , Animais , Apoptose , Cádmio/toxicidade , Chaperona BiP do Retículo Endoplasmático , Camundongos , Espécies Reativas de Oxigênio
8.
Behav Pharmacol ; 32(4): 308-320, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33491993

RESUMO

Alterations of monoamine transmission in mesocorticolimbic regions have been suggested in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). The habenula is an important brain area in regulation of monoamine transmission. In this study, we investigated behavioral and electrophysiological alterations induced by neonatal habenula lesion (NHL) in rats. In NHL rats, age-dependent behavioral alterations relevant to the ADHD symptoms, such as hyperlocomotion, impulsivity, and attention deficit, were observed. Local field potentials (LFPs) in mesocorticolimbic regions of anesthetized rats were examined with in vivo electrophysiological recordings. Abnormally enhanced synchronization of slow (delta) and fast (gamma) LFP oscillations between the amygdala (AMY) and prefrontal cortex (PFC) was found in juvenile, but not in adult, NHL rats. We further examined the effects of an extract and the active compound from the perennial large brown algae Ecklonia stolonifera (ES), which have previously been demonstrated to modulate monoamine transmission, on these NHL-induced alterations. One week of ES extract treatments normalized the NHL-induced behavioral alterations, whereas the active compound fucosterol improved attention deficit and impulsivity, but not hyperlocomotion, in NHL rats. Consistent with the behavioral effects, ES extract treatments also normalized augmented AMY-PFC coupling. These results suggest that altered limbic-cortical information processing may be involved in ADHD-like behavioral alterations induced by NHL, which could be ameliorated by the natural substance, such as ES that affects monoamine transmission.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Atenção/efeitos dos fármacos , Monoaminas Biogênicas/metabolismo , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Habenula , Comportamento Impulsivo , Estigmasterol/análogos & derivados , Transmissão Sináptica/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Modelos Animais de Doenças , Habenula/metabolismo , Habenula/fisiopatologia , Comportamento Impulsivo/efeitos dos fármacos , Comportamento Impulsivo/fisiologia , Phaeophyceae , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Ratos , Estigmasterol/farmacologia
9.
Mar Drugs ; 19(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33557170

RESUMO

Using bio-guided fractionation and based on the inhibitory activities of nitric oxide (NO) and prostaglandin E2 (PGE2), eight isoquinolinequinone derivatives (1-8) were isolated from the marine sponge Haliclona sp. Among these, methyl O-demethylrenierate (1) is a noble ester, whereas compounds 2 and 3 are new O-demethyl derivatives of known isoquinolinequinones. Compound 8 was assigned as a new 21-dehydroxyrenieramycin F. Anti-inflammatory activities of the isolated compounds were tested in a co-culture system of human epithelial Caco-2 and THP-1 macrophages. The isolated derivatives showed variable activities. O-demethyl renierone (5) showed the highest activity, while 3 and 7 showed moderate activities. These bioactive isoquinolinequinones inhibited lipopolysaccharide and interferon gamma-induced production of NO and PGE2. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and the phosphorylation of MAPKs were down-regulated in response to the inhibition of NF-κB nuclear translocation. In addition, nuclear translocation was markedly promoted with a subsequent increase in the expression of HO-1. Structure-activity relationship studies showed that the hydroxyl group in 3 and 5, and the N-formyl group in 7 may be key functional groups responsible for their anti-inflammatory activities. These findings suggest the potential use of Haliclona sp. and its metabolites as pharmaceuticals treating inflammation-related diseases including inflammatory bowel disease.


Assuntos
Anti-Inflamatórios/farmacologia , Haliclona/química , Isoquinolinas/farmacologia , Transporte Ativo do Núcleo Celular , Animais , Células CACO-2 , Heme Oxigenase-1/genética , Humanos , Interferon gama/farmacologia , Isoquinolinas/química , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Relação Estrutura-Atividade , Células THP-1
10.
Mar Drugs ; 19(3)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33809895

RESUMO

By activity-guided fractionation based on inhibition of nitric oxide (NO) and prostaglandin E2 (PGE2), six fistularin compounds (1-6) were isolated from the marine sponge Ecionemia acervus (order Astrophorida). Based on stereochemical structure determination using Mosher's method, fistularin-3 was assigned as a new stereoisomer. On the basis of the stereochemistry of fistularin-3, the stereochemical homogeneity of all six compounds was established by comparing carbon and proton chemical shifts. For fistularin-1 (1) and -2 (2), quantum calculations were performed to confirm their stereochemistry. In a co-culture system of human epithelial Caco-2 cells and THP-1 macrophages, all six isolated compounds showed potent anti-inflammatory activities. These bioactive fistularins inhibited the production of NO, PGE2, TNF-α, IL-1ß, and IL-6 induced by lipopolysaccharide and interferon gamma. Inducible NO synthase and cyclooxygenase-2 expression and MAPK phosphorylation were downregulated in response to the inhibition of NF-κB nuclear translocation. Among the compounds tested, fistularin-1 (1) and 19-deoxyfistularin-3 (4) showed the highest activity. These findings suggest the potential use of the marine sponge E. acervus and its metabolites as pharmaceuticals for the treatment of inflammation-related diseases including inflammatory bowel disease.


Assuntos
Anti-Inflamatórios/farmacologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Isoxazóis/farmacologia , Poríferos/metabolismo , Tirosina/análogos & derivados , Animais , Anti-Inflamatórios/isolamento & purificação , Células CACO-2 , Técnicas de Cocultura , Citocinas/metabolismo , Dinoprostona/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Isoxazóis/isolamento & purificação , Estrutura Molecular , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Transdução de Sinais , Estereoisomerismo , Relação Estrutura-Atividade , Células THP-1 , Tirosina/isolamento & purificação , Tirosina/farmacologia
11.
Biochem Biophys Res Commun ; 533(3): 417-423, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-32972754

RESUMO

Structural transformation of the canonical right-handed helix, B-DNA, to the non-canonical left-handed helix, Z-DNA, can be induced by the Zα domain of the human RNA editing enzyme ADAR1 (hZαADAR1). To characterize the site-specific preferences of binding and structural changes in DNA containing the 2'-O-methyl guanosine derivative (mG), titration of the imino proton spectra and chemical shift perturbations were performed on hZαADAR1 upon binding to Z-DNA. The structural transition between B-Z conformation as the changing ratio between DNA and protein showed a binding affinity of the modified DNA onto the Z-DNA binding protein similar to wild-type DNA or RNA. The chemical shift perturbation results showed that the overall structure and environment of the modified DNA revealed DNA-like properties rather than RNA-like characteristics. Moreover, we found evidence for two distinct regimes, "Z-DNA Sensing" and "Modification Sensing", based on the site-specific chemical shift perturbation between the DNA (or RNA) binding complex and the modified DNA-hZαADAR1 complex. Thus, we propose that modification of the sugar backbone of DNA with 2'-O-methyl guanosine promotes the changes in the surrounding α3 helical structural segment as well as the non-perturbed feature of the ß-hairpin region.


Assuntos
Adenosina Desaminase/química , DNA de Forma B/química , DNA Forma Z/química , Proteínas de Ligação a RNA/química , Adenosina Desaminase/metabolismo , DNA/química , DNA de Forma B/metabolismo , DNA Forma Z/metabolismo , Guanosina/química , Humanos , Modelos Moleculares , Ressonância Magnética Nuclear Biomolecular , Domínios Proteicos , Proteínas de Ligação a RNA/metabolismo
12.
Biomacromolecules ; 21(12): 4795-4805, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-32955865

RESUMO

Although biological therapies based on growth factors and transplanted cells have demonstrated some positive outcomes for intervertebral disc (IVD) regeneration, repeated injection of growth factors and cell leakage from the injection site remain considerable challenges for human therapeutic use. Herein, we prepare human bone marrow-derived mesenchymal stem cells (hBMSCs) and transforming growth factor-ß3 (TGF-ß3)-loaded porous particles with a unique leaf-stack structural morphology (LSS particles) as a combination bioactive delivery matrix for degenerated IVD. The LSS particles are fabricated with clinically acceptable biomaterials (polycaprolactone and tetraglycol) and procedures (simple heating and cooling). The LSS particles allow sustained release of TGF-ß3 for 18 days and stable cell adhesiveness without additional modifications of the particles. On the basis of in vitro and in vivo studies, it was observed that the hBMSCs/TGF-ß3-loaded LSS particles can provide a suitable milieu for chondrogenic differentiation of hBMSCs and effectively induce IVD regeneration in a beagle dog model. Thus, therapeutically loaded LSS particles offer the promise of an effective bioactive delivery system for regeneration of various tissues including IVD.


Assuntos
Disco Intervertebral , Células-Tronco Mesenquimais , Regeneração , Fator de Crescimento Transformador beta3/farmacologia , Animais , Diferenciação Celular , Cães , Humanos , Porosidade
13.
Behav Pharmacol ; 30(7): 596-604, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503068

RESUMO

Engelhardtia chrysolepis Hance (ECH) is a perennial plant used in traditional medicine. A major active ingredient of ECH is astilbin (ASB), which has recently been shown to have neuroprotective effects as well as to affect catecholamine neurotransmissions in brain areas such as the prefrontal cortex. In this study, we investigated the effects of ECH and ASB on long-term memory in mice using a battery of behavioral tests. Acute ECH treatments dose-dependently facilitated nonspatial, but not spatial, memory. ECH treatments also upregulated expression of tyrosine hydroxylase, the enzyme mediating catecholamine synthesis, in neuroblastoma cell culture. Acute ASB treatments similarly improved nonspatial memory, whereas chronic ASB treatments improved both nonspatial and spatial memory. In accordance with such behavioral effects, the increased ratio of tissue concentrations of dopamine metabolites over dopamine in striatal regions was observed in mice with chronic ASB treatments. These results suggest that ECH and its active ingredient ASB may facilitate long-term memory by modulating catecholamine transmission.


Assuntos
Flavonóis/farmacologia , Memória de Longo Prazo/efeitos dos fármacos , Animais , Catecolaminas/metabolismo , Fagales/metabolismo , Juglandaceae/metabolismo , Masculino , Aprendizagem em Labirinto , Medicina Tradicional/métodos , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Córtex Pré-Frontal/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo
14.
Mar Drugs ; 17(11)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31717394

RESUMO

The inflammatory bowel diseases (IBD) cause chronic inflammation of the gastrointestinal tract and include ulcerative colitis (UC) and Crohn's disease (CD). The prevalence of IBD has been increasing worldwide, and has sometimes led to irreversible impairment of gastrointestinal structure and function. In the present study, we successfully isolated a new phylloketal derivative, deacetylphylloketal (1) along with four known compounds from the sponge genus Phyllospongia. The anti-inflammatory properties of deacetylphylloketal (1) and phyllohemiketal A (2) were evaluated using an in vitro co-culture system that resembles the intestinal epithelial environment. A co-culture system was established that consisted of human epithelial Caco-2 cells and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage cells. The treatment of co-cultured THP-1 cells with compounds 1 or 2 significantly suppressed the production and/or gene expression of lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), Interleukin-6 (IL-6), IL-1ß and Tumor Necrosis Factor alpha (TNF-α). The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 were down-regulated in response to inhibition of NF-kB translocation into the nucleus in cells. In addition, we observed that 1 and 2 markedly promoted the nuclear translocation of Nrf2 and subsequent increase in the expression of heme oxygernase (HO)-1. These findings suggest the potential use of sponge genus Phyllospongia and its metabolites as a pharmaceutical aid in the treatment of inflammation-related diseases including IBD.


Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Poríferos/química , Sesterterpenos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Células CACO-2 , Linhagem Celular , Técnicas de Cocultura , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Sesterterpenos/isolamento & purificação
15.
Molecules ; 24(18)2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31540496

RESUMO

Crohn's disease (CD) and ulcerative colitis (UC), collectively referred to as inflammatory bowel disease (IBD), are autoimmune diseases characterized by chronic inflammation within the gastrointestinal tract. Debromohymenialdisine is an active pyrrole alkaloid that is well known to serve as a stable and effective inhibitor of Chk2. In the present study, we attempted to investigate the anti-inflammatory properties of (10Z)-debromohymenialdisine (1) isolated from marine sponge Stylissa species using an intestinal in vitro model with a transwell co-culture system. The treatment with 1 attenuated the production and gene expression of lipopolysaccharide (LPS)-induced Interleukin (IL)-6, IL-1ß, prostaglandin E2 (PGE2), and tumor necrosis factor-α in co-cultured THP-1 macrophages at a concentration range of 1-5 µM. The protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were down-regulated in response to the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) translocation into the nucleus in cells. In addition, we observed that 1 markedly promoted the nuclear translocation of nuclear factor erythroid 2 related factor 2 (Nrf2) and subsequent increase of heme oxygenase-1 (HO-1) expression. These findings suggest the potential use of 1 as a pharmaceutical lead in the treatment of inflammation-related diseases including IBD.


Assuntos
Organismos Aquáticos/química , Azepinas/farmacologia , Colite Ulcerativa , Doença de Crohn , Intestinos/patologia , Poríferos/química , Pirróis/farmacologia , Animais , Azepinas/química , Células CACO-2 , Técnicas de Cocultura , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Dinoprostona/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Pirróis/química , Células THP-1
16.
Molecules ; 23(11)2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30355979

RESUMO

Z-DNA is stabilized by various Z-DNA binding proteins (ZBPs) that play important roles in RNA editing, innate immune response, and viral infection. In this review, the structural and dynamics of various ZBPs complexed with Z-DNA are summarized to better understand the mechanisms by which ZBPs selectively recognize d(CG)-repeat DNA sequences in genomic DNA and efficiently convert them to left-handed Z-DNA to achieve their biological function. The intermolecular interaction of ZBPs with Z-DNA strands is mediated through a single continuous recognition surface which consists of an α3 helix and a ß-hairpin. In the ZBP-Z-DNA complexes, three identical, conserved residues (N173, Y177, and W195 in the Zα domain of human ADAR1) play central roles in the interaction with Z-DNA. ZBPs convert a 6-base DNA pair to a Z-form helix via the B-Z transition mechanism in which the ZBP first binds to B-DNA and then shifts the equilibrium from B-DNA to Z-DNA, a conformation that is then selectively stabilized by the additional binding of a second ZBP molecule. During B-Z transition, ZBPs selectively recognize the alternating d(CG)n sequence and convert it to a Z-form helix in long genomic DNA through multiple sequence discrimination steps. In addition, the intermediate complex formed by ZBPs and B-DNA, which is modulated by varying conditions, determines the degree of B-Z transition.


Assuntos
DNA Forma Z/química , Proteínas de Ligação a DNA/química , DNA/química , Modelos Moleculares , Termodinâmica , Algoritmos , Sítios de Ligação , Proteínas de Ligação a DNA/metabolismo , Substâncias Macromoleculares/química , Substâncias Macromoleculares/metabolismo , Conformação Proteica , Relação Estrutura-Atividade
17.
Biol Pharm Bull ; 40(11): 1856-1865, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29093332

RESUMO

Halophyte Limonium tetragonum has recently been of interest in Korea for its nutritional value and salty taste which made it an ideal vegetable. In this study, the potential of L. tetragonum preventing excess weight gain, obesity and the related health problem has been evaluated in vitro and in vivo. The treatment with 100 mg/kg of L. tetragonum EtOAc soluble fraction (EALT) apparently prevented the body weight gain, adipose tissue weight gain, and the increase of triglyceride and total cholesterol level in mice fed a high-fat diet for 8 weeks. In addition, both glucose tolerance and insulin resistance in dietary obese mice were improved by EALT administration. A marked decrease in adipocyte differentiation was observed in the EALT (50 µg/mL)-treated 3T3-L1 cells, which was mediated by the suppression of adipogenesis-related transcription factors including peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer binding protein (C/EBP)α, and Sterol regulatory element binding protein-1 (SREBP-1) and adipocyte-specific proteins such as fatty acid synthase (FAS), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein (aP2). The major components contained in EALT were identified as (-)-epigallocatechin-3-(3″-O-methyl) gallate, (-)-epigallocatechin-3-gallate, and myricetin-3-O-ß-D-galactopyranoside based on its phytochemical analysis. Results suggested that EALT might be available as functional crop and bioactive diet supplement for the prevention and/or treatment of obesity.


Assuntos
Adipogenia/efeitos dos fármacos , Fármacos Antiobesidade/uso terapêutico , Obesidade/prevenção & controle , Extratos Vegetais/uso terapêutico , Plumbaginaceae/química , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Fármacos Antiobesidade/farmacologia , Glicemia , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Modelos Animais de Doenças , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/sangue , Obesidade/etiologia , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/farmacologia , República da Coreia , Triglicerídeos/sangue , Aumento de Peso/efeitos dos fármacos
18.
BMC Health Serv Res ; 17(1): 661, 2017 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-28915814

RESUMO

BACKGROUND: To examine whether medication related information processing defined as reading of over-the-counter drug labels, understanding prescription instructions, and information seeking-and medication adherence account for the association between health literacy and quality of life, and whether these associations may be moderated by age and gender. METHODS: A sample of 305 adults in South Korea was recruited through a proportional quota sampling to take part in a cross-sectional survey on health literacy, medication-related information processing, medication adherence, and quality of life. Descriptive statistics and structural equation modeling (SEM) were performed. RESULTS: Two mediation pathways linking health literacy with quality of life were found. First, health literacy was positively associated with reading drug labels, which was subsequently linked to medication adherence and quality of life. Second, health literacy was positively associated with accurate understanding of prescription instructions, which was associated with quality of life. Age moderation was found, as the mediation by reading drug labels was significant only among young adults whereas the mediation by understanding of medication instruction was only among older adults. CONCLUSION: Reading drug labels and understanding prescription instructions explained the pathways by which health literacy affects medication adherence and quality of life. The results suggest that training skills for processing medication information can be effective to enhance the health of those with limited health literacy.


Assuntos
Compreensão , Rotulagem de Medicamentos , Letramento em Saúde , Adesão à Medicação , Qualidade de Vida , Adulto , Estudos Transversais , Feminino , Letramento em Saúde/estatística & dados numéricos , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , República da Coreia , Inquéritos e Questionários , Adulto Jovem
20.
J Adhes Dent ; 19(1): 21-29, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28195275

RESUMO

PURPOSE: To evaluate the effects of tribochemical silica coating and different 10-methacryloyloxydecyl dihydrogen phosphate (MDP)-containing primers on the shear bond strength (SBS) of orthodontic metal brackets to yttrium-stabilized tetragonal zirconia polycrystal (Y-TZP) surfaces. MATERIALS AND METHODS: One hundred ninety polished Y-TZP specimens were randomly assigned to 19 groups (n = 10): 30 specimens were used for surface analyses after polishing with 600-grit silicon carbide paper, airborneparticle abrasion with 50-µm alumina (A), or tribochemical silica coating (CoJet [C]); 160 specimens were used in SBS testing of orthodontic metal brackets to Y-TZP after alumina airborne-particle abrasion or tribochemical silica coating and application of either ESPE-Sil (S) (ASn, ASa, CSn, CSa), Alloy Primer (AP) (AAPn, AAPa, CAPn, CAPa), Clearfil Ceramic Primer (CP) (ACPn, ACPa, CCPn, CCPa), or Scotchbond Universal (U) (AUn, AUa, CUn, CUa) and either stored in water for 24 h (non-aged, n) or thermocycled 5000 times (aged, a). The surface analyses and SBSs were statistically analyzed with ANOVA and Tukey's tests. RESULTS: Both mechanically treated surfaces had significantly greater surface roughness and surface free energy than did the polished surfaces. The type of primer and aging significantly affected the bond strength. Among the thermocycled specimens, the AAPa, AUa, and CCPa groups showed the greatest SBS. CONCLUSION: After alumina airborne-particle abrasion, the application of Alloy Primer, Clearfil Ceramic Primer, or Scotchbond Universal provided stable bonding to Y-TZP ceramics. After tribochemical silica coating, however, only Clearfil Ceramic Primer produced a durable bond to Y-TZP ceramics.


Assuntos
Colagem Dentária , Metacrilatos , Braquetes Ortodônticos , Dióxido de Silício , Zircônio , Teste de Materiais , Distribuição Aleatória , Propriedades de Superfície
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