Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 36
Filtrar
1.
Inorg Chem ; 60(24): 19328-19335, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34865466

RESUMO

Ethylene (C2H4) is one of the most significant substances in the petrochemical industry; however, the capture of acetylene (C2H2) in about 1% from C2H2/C2H4 mixtures is a difficult task because of the similarity of their physical properties. With the aggravation of the energy crisis, using metal-organic framework (MOF) materials to purify C2H4 through adsorptive separation is a promising way to save energy and reduce emission. Pore-space partition (PSP) with the aim of enhancing the density of the binding sites and the strength of the host-guest interactions is an effective means to promote a solution for the challenging gas separation problems. Herein, we report a new embedding metal-carboxylate chain-induced topology upgrade strategy within a MOF to realize PSP and separation of C2H2/C2H4 mixtures. As a proof of concept, we construct a microporous MOF (NUM-12) utilizing the in situ insertion of cobalt terephthalic chains into a pretargeted ant-type framework during synthesis. Because of the attainment of an elaborately tuned aperture size and a specific pore environment through this strategy, NUM-12a (activated NUM-12) not only has a remarkable gas sorption capacity and strong interactions for C2H2 but also possesses an excellent purification performance for C2H2/C2H4 mixtures. Both experiments and simulation calculations clearly reveal that NUM-12 is a promising candidate for the separation of C2H2/C2H4, proving the feasibility of this new strategy for developing newly fashioned MOFs with adjustable structure and performance.

2.
Biomolecules ; 11(11)2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34827605

RESUMO

The subcellular locations of proteins are closely related to their functions. In the past few decades, the application of machine learning algorithms to predict protein subcellular locations has been an important topic in proteomics. However, most studies in this field used only amino acid sequences as the data source. Only a few works focused on other protein data types. For example, three-dimensional structures, which contain far more functional protein information than sequences, remain to be explored. In this work, we extracted various handcrafted features to describe the protein structures from physical, chemical, and topological aspects, as well as the learned features obtained by deep neural networks. We then used these features to classify the protein subcellular locations. Our experimental results demonstrated that some of these structural features have a certain effect on the protein location classification, and can help improve the performance of sequence-based location predictors. Our method provides a new view for the analysis of protein spatial distribution, and is anticipated to be used in revealing the relationships between protein structures and functions.


Assuntos
Proteínas , Sequência de Aminoácidos , Biologia Computacional , Bases de Dados de Proteínas , Redes Neurais de Computação
3.
World J Clin Cases ; 9(16): 3796-3813, 2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34141737

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is spreading at an alarming rate, and it has created an unprecedented health emergency threatening tens of millions of people worldwide. Previous studies have indicated that SARS-CoV-2 ribonucleic acid could be detected in the feces of patients even after smear-negative respiratory samples. However, demonstration of confirmed fecal-oral transmission has been difficult. Clinical studies have shown an incidence rate of gastrointestinal (GI) symptoms ranging from 2% to 79.1% in patients with COVID-19. They may precede or accompany respiratory symptoms. The most common GI symptoms included nausea, diarrhea, and abdominal pain. In addition, some patients also had liver injury, pancreatic damage, and even acute mesenteric ischemia/thrombosis. Although the incidence rates reported in different centers were quite different, the digestive system was the clinical component of the COVID-19 section. Studies have shown that angiotensin-converting enzyme 2, the receptor of SARS-CoV-2, was not only expressed in the lungs, but also in the upper esophagus, small intestine, liver, and colon. The possible mechanism of GI symptoms in COVID-19 patients may include direct viral invasion into target cells, dysregulation of angiotensin-converting enzyme 2, immune-mediated tissue injury, and gut dysbiosis caused by microbiota. Additionally, numerous experiences, guidelines, recommendations, and position statements were published or released by different organizations and societies worldwide to optimize the management practice of outpatients, inpatients, and endoscopy in the era of COVID-19. In this review, based on our previous work and relevant literature, we mainly discuss potential fecal-oral transmission, GI manifestations, abdominal imaging findings, relevant pathophysiological mechanisms, and infection control and prevention measures in the time of COVID-19.

4.
J Agric Food Chem ; 69(25): 7016-7027, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34060828

RESUMO

Daily intake of tea has been known to relate to a low risk of depression. In this study, we report that a special variety of tea in China, Camellia assamica var. kucha (kucha), possesses antidepressant effects but with less adverse effects as compared to traditional tea Camellia sinensis. This action of kucha is related to its high amount of theacrine, a purine alkaloid structurally similar to caffeine. We investigated the antidepressant-like effects and mechanisms of theacrine in chronic water immersion restraint stress and chronic unpredictable mild stress mice models. PC12 cells and primary hippocampal neural stem cells were treated with stress hormone corticosterone (CORT) to reveal the potential antidepression mechanism of theacrine from the perspective of adult hippocampus neurogenesis. Results of behavioral and neurotransmitter analysis showed that intragastric administration of theacrine significantly counteracted chronic stress-induced depression-like disorders and abnormal 5-hydroxytryptamine (5-HT) metabolism with less central excitability. Further investigation from both in vivo and in vitro experiments indicated that the antidepressant mechanism of theacrine was associated with promoting adult hippocampal neurogenesis, via the modulation of the phosphodiesterase-4 (PDE4)/cyclic adenosine monophosphate (cAMP)/cAMP response-element binding (CREB)/brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway. Collectively, our findings could promote the prevalence of kucha as a common beverage with uses for health care and contribute to the development of theacrine as a potential novel antidepressant medicine.


Assuntos
Alcaloides , Camellia sinensis , Animais , Antidepressivos , Fator Neurotrófico Derivado do Encéfalo/genética , China , Depressão/tratamento farmacológico , Hipocampo , Camundongos , Neurogênese , Purinas , Ratos , Estresse Psicológico , Chá , Ácido Úrico/análogos & derivados
5.
Nat Chem Biol ; 17(4): 465-476, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542532

RESUMO

Ferroptosis, triggered by discoordination of iron, thiols and lipids, leads to the accumulation of 15-hydroperoxy (Hp)-arachidonoyl-phosphatidylethanolamine (15-HpETE-PE), generated by complexes of 15-lipoxygenase (15-LOX) and a scaffold protein, phosphatidylethanolamine (PE)-binding protein (PEBP)1. As the Ca2+-independent phospholipase A2ß (iPLA2ß, PLA2G6 or PNPLA9 gene) can preferentially hydrolyze peroxidized phospholipids, it may eliminate the ferroptotic 15-HpETE-PE death signal. Here, we demonstrate that by hydrolyzing 15-HpETE-PE, iPLA2ß averts ferroptosis, whereas its genetic or pharmacological inactivation sensitizes cells to ferroptosis. Given that PLA2G6 mutations relate to neurodegeneration, we examined fibroblasts from a patient with a Parkinson's disease (PD)-associated mutation (fPDR747W) and found selectively decreased 15-HpETE-PE-hydrolyzing activity, 15-HpETE-PE accumulation and elevated sensitivity to ferroptosis. CRISPR-Cas9-engineered Pnpla9R748W/R748W mice exhibited progressive parkinsonian motor deficits and 15-HpETE-PE accumulation. Elevated 15-HpETE-PE levels were also detected in midbrains of rotenone-infused parkinsonian rats and α-synuclein-mutant SncaA53T mice, with decreased iPLA2ß expression and a PD-relevant phenotype. Thus, iPLA2ß is a new ferroptosis regulator, and its mutations may be implicated in PD pathogenesis.


Assuntos
Ferroptose/fisiologia , Fosfolipases A2 do Grupo VI/metabolismo , Animais , Araquidonato 15-Lipoxigenase/metabolismo , Modelos Animais de Doenças , Feminino , Fosfolipases A2 do Grupo VI/fisiologia , Humanos , Ferro/metabolismo , Leucotrienos/metabolismo , Metabolismo dos Lipídeos/fisiologia , Peróxidos Lipídicos/metabolismo , Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , Doença de Parkinson/metabolismo , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Fosfolipases/metabolismo , Fosfolipídeos/metabolismo , Ratos , Ratos Endogâmicos Lew
6.
Life Sci ; 270: 119061, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33454364

RESUMO

For patients with hepatocellular carcinoma (HCC), early detection is critical to improve survival. Secreted frizzled-related protein 2 (SFRP2) is a candidate tumor suppressor as Wnt antagonist and SFRP2 promoter has been found hypermethylated in various malignancies. This study aimed to investigate the methylation status of SFRP2 promoter in hepatitis B virus (HBV) associated HCC and estimate its diagnostic value as a non-invasive biomarker. A total of 293 patients, including 132 patients with HBV-associated HCC, 121 with chronic hepatitis B (CHB) and 40 healthy controls (HCs) were enrolled. SFRP2 methylation level in peripheral mononuclear cells (PBMCs) was quantitatively detected by MethyLight. SFRP2 methylation level was significantly higher in patients with HBV-associated HCC than in those with CHB (p < 0.001) and HCs (p < 0.001) while mRNA level of SFRP2 was significantly lower in HCC group than the other two groups (p < 0.05). In HCC subgroup, SFRP2 methylation level markedly increased in patients >50 years old, female, with negative HBeAg, negative HBV-DNA and poor differentiation compared with the remaining groups (P < 0.05). Furthermore, SFRP2 methylation level showed a significantly better diagnostic value than alpha-fetoprotein (AFP) and the combination of AFP and methylation levels of SFRP2 markedly improved the area under the receiver operating characteristic curve (p < 0.05). In conclusion, hypermethylation of SFRP2 promoter exists in HBV-associated HCC. The combination of SFRP2 methylation level in PBMCs and AFP could significantly improve the diagnostic ability of AFP in discriminating HBV-associated HCC from CHB and SFRP2 methylation level had the potential to serve as a non-invasive biomarker for HCC diagnosis.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Membrana/genética , Adulto , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Metilação de DNA/genética , Feminino , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , RNA Mensageiro/metabolismo , alfa-Fetoproteínas/genética
7.
Tohoku J Exp Med ; 252(4): 297-307, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33239483

RESUMO

Wnt1-inducible signaling pathway protein 1 (WISP1) regulates cell proliferation, differentiation, adhesion, migration and survival. Abnormal WISP1 expression is associated with the carcinogenesis of hepatocellular carcinoma (HCC). Aberrant DNA methylation is one of the major epigenetic alterations in HCC. However, the methylation status of the WISP1 promoter is still unclear. We therefore aimed to determine the methylation status of the WISP1 promoter and evaluate its clinical value in HCC. The study enrolled 251 participants, including 123 participants with HCC, 90 participants with chronic hepatitis B (CHB) and 38 healthy controls (HCs). WISP1 methylation status, mRNA levels and plasma soluble WISP1 were detected by methylation-specific polymerase chain reaction (MSP), quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. We found that the methylation frequency of WISP1 in patients with HCC was significantly lower than that in patients with CHB and HCs, while the relative expression levels of WISP1 mRNA were markedly higher in patients with HCC than in patients with CHB and HCs. Furthermore, the plasma soluble WISP1 in patients with HCC was obviously lower than in that in patients with CHB and HCs. Alpha-fetoprotein (AFP) is a widely recognized biomarker to diagnose HCC which lacks enough sensitivity and specificity. WISP1 promoter methylation status combined with AFP significantly improved the diagnostic ability in discriminating HCC from CHB compared with AFP or WISP1 methylation status alone. In conclusion, hypomethylation of the WISP1 gene promoter may serve as a noninvasive biomarker for detecting HBV-associated HCC.


Assuntos
Proteínas de Sinalização Intercelular CCN/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Metilação de DNA/genética , Vírus da Hepatite B/fisiologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas/genética , Sequência de Bases , Proteínas de Sinalização Intercelular CCN/sangue , Proteínas de Sinalização Intercelular CCN/metabolismo , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatite B Crônica/genética , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/virologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Proteínas Proto-Oncogênicas/sangue , Proteínas Proto-Oncogênicas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Curva ROC
8.
Sci Rep ; 10(1): 6584, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32313098

RESUMO

Breastfeeding is related to maternal health. However, the association of women's breastfeeding duration with cognitive function in their later life is limited and inconsistent. The aim of this study was to accurately evaluate the association in Chinese postmenopausal women. We analyzed the data from Zhejiang Ageing and Health Cohort Study including 5487 postmenopausal women. Cognitive impairment was assessed via the Mini-Mental State Examination. Data on breastfeeding duration was collected in the reproductive history section within the questionnaire. Generalized additive models (GAMs) and logistic regression models, controlled for an extensive range of potential confounders, were generated to examine the associations. A U-shaped association was identified between breastfeeding duration and cognitive impairment based on GAM. The nadir with lowest odds of cognitive impairment was ascertained by quadratic model as 12 months. The logistic models showed that compared with women breastfeeding 12 months per child, the fully adjusted odds ratios (ORs) were 1.50 (95% Confidence Interval (CI): 1.20-1.88), 1.58 (95% CI: 1.29-1.93), 1.33 (95% CI: 1.06-1.68), 2.08 (95% CI: 1.64-2.65) for those averagely breastfeeding <6, 6-<12,>12-18,>18 months, respectively. Furthermore, we did not observe significant effect modification of the association. Future longitudinal studies are needed to confirm the association.


Assuntos
Aleitamento Materno , Disfunção Cognitiva/fisiopatologia , Pós-Menopausa/fisiologia , Adulto , Idoso , China/epidemiologia , Cognição/fisiologia , Disfunção Cognitiva/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Fatores Socioeconômicos , Fatores de Tempo
9.
Mol Nutr Food Res ; 64(3): e1901019, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31860939

RESUMO

SCOPE: Dietary advanced glycation products (dAGEs) have been reported to induce cognitive impairment while quercetin possesses potential neuroprotective effects. The aim is to explore whether dAGEs would induce similar cognitive impairment from both young and aged ICR mice, and the protective effects of quercetin. METHODS AND RESULTS: A total of 32 aged ICR mice (15-month-old) and 16 young ICR mice (3-month-old) are randomly assigned into the following six groups: Young mice control group, young mice fed with AGEs diet group, old mice control group, old mice fed with AGEs diet group, old mice with quercetin supplemented diet group, old mice fed with AGE diet supplemented with quercetin group. Dietary AGEs induced cognitive impairment only in aged, but not in young, ICR mice, while quercetin intervention is capable of reversing dAGEs-induced cognitive dysfunction. This may be since quercetin 1) increased miR-219, miR-15a, and miR-132 expression, inhibited p-ERK1/2, and tau phosphorylation; and 2) improved gut microbiota richness and diversity, inhibited phylum Tenericutes and Proteobacteria, and elevated butyric acid from cecum. CONCLUSION: Prolonged application of quercetin may be beneficial in the elderly, especially for those with high consumption of dAGEs.


Assuntos
Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Produtos Finais de Glicação Avançada/toxicidade , Quercetina/farmacologia , Fatores Etários , Peptídeos beta-Amiloides/metabolismo , Animais , Ceco/metabolismo , Envelhecimento Cognitivo , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos Endogâmicos ICR , MicroRNAs , Teste do Labirinto Aquático de Morris , Fármacos Neuroprotetores/farmacologia , RNA Ribossômico 16S , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo
10.
Transl Cancer Res ; 9(9): 5493-5507, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35117914

RESUMO

BACKGROUND: It has been proved that DNA methylation, as an epigenetic regulatory mode, plays a crucial role in the initiation, progression and invasion of hepatocellular carcinoma (HCC). However, there still are some pathways and factors that regulates the carcinogenesis of HCC remains unclear. METHODS: The original datasets comparing DNA methylation, clinical information and transcriptome profiling between HCC and normal controls were downloaded from The Cancer Genome Atlas (TCGA) database. R software was used to screen for methylation-differential genes (MDGs) and methylation-driven genes. Gene-functional enrichment analysis, ConsensusPathDB pathway analysis, protein-protein interaction (PPI) network construction and survival analysis were performed; methylation-specific polymerase chain reaction (MSP) and real-time quantitative polymerase chain reaction (RT-qPCR) were used for validation. RESULTS: One hundred and sixty-seven MDGs and 285 methylation-driven genes were identified. Function and pathway enrichment analysis revealed that they are associated with sequence-specific DNA binding, nuclear nucleosome, regulation of insulin-like growth factor transport, etc. An eight-gene (HIST1H1D, RP11-476B1.1, OR2AK2, TNFRSF12A, CTD-2313N18.8, AC133644.2, RP11-467L13.4 and LINC00989) prognostic model was identified from the MDGs; its methylation degree can strongly predict the overall survival of HCC. Among them, TNFRSF12A being the only one belongs to both MDGs and methylation-driver genes, shows a significant independent correlation with the prognosis of HCC. That was validated in further details. CONCLUSIONS: Our research has identified a registry of novel genes and pathways that's important for regulating the carcinogenesis of HCC. In addition, we identified a strong molecular model for prognostic prediction. These findings will not only provide guidance for clinical individualized treatment, but also to set us targets for further research on the molecular mechanism of HCC.

12.
Br J Pharmacol ; 176(18): 3695-3711, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31222723

RESUMO

BACKGROUND AND PURPOSE: We have shown that cholesterol is synthesized in the principal cells of renal cortical collecting ducts (CCD) and stimulates the epithelial sodium channels (ENaC). Here we have determined whether lovastatin, a cholesterol synthesis inhibitor, can antagonize the hypertension induced by activated ENaC, following deletion of the cholesterol transporter (ATP-binding cassette transporter A1; ABCA1). EXPERIMENTAL APPROACH: We selectively deleted ABCA1 in the principal cells of mouse CCD and used the cell-attached patch-clamp technique to record ENaC activity. Western blot and immunofluorescence staining were used to evaluate protein expression levels. Systolic BP was measured with the tail-cuff method. KEY RESULTS: Specific deletion of ABCA1 elevated BP and ENaC single-channel activity in the principal cells of CCD in mice. These effects were antagonized by lovastatin. ABCA1 deletion elevated intracellular cholesterol levels, which was accompanied by elevated ROS, increased expression of serum/glucocorticoid regulated kinase 1 (Sgk1), phosphorylated neural precursor cell-expressed developmentally down-regulated protein 4-2 (Nedd4-2) and furin, along with shorten the primary cilium, and reduced ATP levels in urine. CONCLUSIONS AND IMPLICATIONS: These data suggest that specific deletion of ABCA1 in principal cells increases BP by stimulating ENaC channels via a cholesterol-dependent pathway which induces several secondary responses associated with oxidative stress, activated Sgk1/Nedd4-2, increased furin expression, and reduced cilium-mediated release of ATP. As ABCA1 can be blocked by cyclosporine A, these results suggest further investigation of the possible use of statins to treat CsA-induced hypertension.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/genética , Anti-Hipertensivos/uso terapêutico , Bloqueadores do Canal de Sódio Epitelial/uso terapêutico , Hipertensão/tratamento farmacológico , Lovastatina/uso terapêutico , Animais , Anticolesterolemiantes/farmacologia , Anti-Hipertensivos/farmacologia , Bloqueadores do Canal de Sódio Epitelial/farmacologia , Canais Epiteliais de Sódio/fisiologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Túbulos Renais/metabolismo , Lovastatina/farmacologia , Masculino , Camundongos Knockout
13.
Biochim Biophys Acta Mol Basis Dis ; 1865(7): 1915-1924, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31109455

RESUMO

We have previously shown that blockade of ATP-binding cassette transporter A1 (ABCA1) with cyclosporine A (CsA) stimulates the epithelial sodium channel (ENaC) in cultured distal nephron cells. Here we show that CsA elevated systolic blood pressure in both wild-type and apolipoprotein E (ApoE) knockout (KO) mice to a similar level. The elevated systolic blood pressure was completely reversed by inhibition of cholesterol (Cho) synthesis with lovastatin. Inside-out patch-clamp data show that intracellular Cho stimulated ENaC in cultured distal nephron cells by interacting with phosphatidylinositol­4,5­bisphosphate (PIP2), an ENaC activator. Confocal microscopy data show that both α­ENaC and PIP2 were localized in microvilli via a Cho-dependent mechanism. Deletion of membrane Cho reduced the levels of γ­ENaC in the apical membrane. Reduced ABCA1 expression and elevated intracellular Cho were observed in old mice, compared to young mice. In parallel, cell-attached patch-clamp data from the split-open cortical collecting ducts (CCD) show that ENaC activity was significantly increased in old mice. These data suggest that elevation of intracellular Cho due to blockade of ABCA1 stimulates ENaC, which may contribute to CsA-induced hypertension. This study also implies that reduced ABCA1 expression may mediate age-related hypertension by increasing ENaC activity via elevation of intracellular Cho.


Assuntos
Colesterol/metabolismo , Ciclosporina/efeitos adversos , Inibidores Enzimáticos/efeitos adversos , Canais Epiteliais de Sódio/metabolismo , Hipertensão/induzido quimicamente , Transportador 1 de Cassete de Ligação de ATP/antagonistas & inibidores , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Linhagem Celular , Hipertensão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fosfatos de Fosfatidilinositol/metabolismo , Xenopus
14.
BMJ Open ; 8(12): e023188, 2018 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-30552262

RESUMO

OBJECTIVE: To analyse the independent and combined associations of postlunch napping duration and night-time sleep duration with risk of cognitive impairment among Chinese elderly. DESIGN: A cross-sectional study. SETTING: We analysed the data from Zhejiang Ageing and Health Cohort, a population-based survey of seven counties located in Zhejiang province in eastern China. PARTICIPANTS: 10 740 participants aged 60 years or older were included in final analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: Cognitive impairment was assessed through Mini-Mental State Examination. Data on sleep-related characteristics was collected in the behavioural habits section within the questionnaire. RESULTS: Relative to participants with 1-30 min of postlunch napping, those who did not nap and who napped longer had significantly higher risks for cognitive impairment. OR of cognitive impairment were 1.41 (95% CI 1.14 to 1.75) for participants with longer night-time sleep duration (≥9 hours), compared with those sleeping 7-8.9 hours. In addition, combined effects were further identified. Participants with both longer night-time sleep duration (≥9 hours) and longer postlunch napping duration (>60 min) (OR=2.01, 95% CI 1.30 to 3.13), as well as those with both longer night-time sleep duration (≥9 hours) and appropriate postlunch napping duration (1-30 min) (OR=2.01, 95% CI 1.20 to 3.38), showed significantly higher risk of cognitive impairment than those with sleeping 7-8 hours and napping 1-30 min. Meanwhile, a 34% increase in odds of cognitive impairment was observed in participants with both shorter night-time sleep duration (5-6.9 hours) and no napping. CONCLUSION: Both postlunch napping duration and night-time sleep duration were independently and jointly associated with cognitive impairment, which needs verification in prospective studies.


Assuntos
Ritmo Circadiano , Disfunção Cognitiva/etiologia , Almoço , Sono , Idoso , Idoso de 80 Anos ou mais , China , Estudos de Coortes , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Vigilância da População , Fatores de Risco , Fatores de Tempo
15.
Cell Physiol Biochem ; 47(3): 1051-1059, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29843130

RESUMO

BACKGROUND/AIMS: The epithelial sodium channel (ENaC) in cortical collecting duct (CCD) principal cells plays a critical role in regulating systemic blood pressure. We have previously shown that cholesterol (Cho) in the apical cell membrane regulates ENaC; however, the underlying mechanism remains unclear. METHODS: Patch-clamp technique and confocal microscopy were used to evaluate ENaC activity and density. RESULTS: Here we show that extraction of membrane Cho with methyl-ß-cyclodextrin (MßCD) significantly reduced amiloride-sensitive current and ENaC single-channel activity. The effects were reproduced by inhibition of Cho synthesis in the cells with lovastatin. We have previously shown that phosphatidylinositol-4,5-bisphosphate (PIP2), an ENaC activator, is predominantly located in the microvilli, a specialized apical membrane domain. Here, our confocal microscopy data show that α-ENaC was co-localized with PIP2 in the microvilli and that Cho was also co-localized with PIP2 in the microvilli. Either extraction of Cho with MßCD or inhibition of Cho synthesis with lovastatin consistently reduced the levels of Cho, PIP2, and ENaC in the microvilli. CONCLUSIONS: Since PIP2 can directly stimulate ENaC and also affect ENaC trafficking, these data suggest that depletion of Cho reduces ENaC apical density and activity at least in part by decreasing PIP2 in the microvilli.


Assuntos
Colesterol/metabolismo , Canais Epiteliais de Sódio/metabolismo , Túbulos Renais Coletores/metabolismo , Microvilosidades/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Animais , Proteínas de Xenopus , Xenopus laevis , beta-Ciclodextrinas/farmacologia
16.
Metabolism ; 85: 227-239, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29727630

RESUMO

OBJECTIVE: Acylcarnitine metabolism disorder contributes significantly to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). There are, however, few ideal medications for NAFLD, which work by targeting acylcarnitine metabolism. The aim of this study was to investigate the protective effects of theacrine, a rare purine alkaloid isolated from Camellia assamica var. kucha, against acylcarnitine metabolism disorder in NAFLD. METHODS: The pharmacological activities of theacrine were studied using high-fat diet (HFD)-fed ApoE-/- and C57BL/6J mice models. Oleate-treated HepG2 and L-02 cells were used to investigate the molecular mechanism of theacrine on acylcarnitine metabolism. The target of theacrine was confirmed in vitro as the blockade of sirtuin 3 (SIRT3) and protein kinase A. RESULTS: Theacrine inhibits hepatic steatosis and liver inflammation and improves energy expenditure in HFD-fed mice. Theacrine ameliorates acylcarnitine metabolism disorder in HFD-fed mice and oleate-treated hepatocytes by improving fatty acid oxidation. The underlying mechanism involves theacrine's activation of the mitochondrial deacetylase SIRT3 and consequently, the increased activity of long-chain acyl coenzyme A dehydrogenase (LCAD) through deacetylation. CONCLUSION: Theacrine promotes acylcarnitine metabolism in NAFLD through the SIRT3/LCAD signaling pathway. The target of theacrine's activities on NAFLD is identified as SIRT3.


Assuntos
Carnitina/análogos & derivados , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Ácido Úrico/análogos & derivados , Animais , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Carnitina/metabolismo , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácido Oleico , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ácido Úrico/farmacologia , Ácido Úrico/uso terapêutico
17.
Oncol Res ; 26(3): 483-494, 2018 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-28550687

RESUMO

Oral submucous fibrosis (OSF) induced by chewing of the areca nut has been considered to be a precancerous lesion with a high probability of developing oral squamous cell carcinoma. Tanshinone (TSN) is the main component extracted from Salvia miltiorrhiza, a traditional Chinese medicine, which was found to have diverse pharmacological effects, such as anti-inflammatory and antitumor. In the current study, we aimed to identify the inhibitory effects and the underlying mechanism of TSN on OSF progress. We found that treatment with TSN inhibited the arecoline-mediated proliferation of primary human oral mucosal fibroblasts and reversed the promotive effects of arecoline on the EMT process. By RNA deep sequencing, we screened two possible targets for TSN: LSD1 and p53. We confirmed that p53 is much lower in OSF than in normal mucous tissues. In addition, p53 and its downstream molecules were decreased by arecoline treatment in oral mucosal fibroblasts, which was reversed by treatment with TSN in a dose-dependent manner. Our results also revealed that arecoline stimulation resulted in hypermethylation of the promoter of TP53 and subsequent downregulation of p53 levels, which was reversed by TSN. Furthermore, we identified that LSD1 could epigenetically activate TP53 by recruiting H3K27me1 and H3K4m2 to its promoter. Our findings provide new insights into the mechanism by which TSN influences arecoline-induced OSF and rationale for the development of clinical intervention strategies for OSF and even oral squamous cell carcinoma.


Assuntos
Abietanos/farmacologia , Areca/química , Arecolina/toxicidade , Transição Epitelial-Mesenquimal , Mucosa Bucal/patologia , Fibrose Oral Submucosa/patologia , Proteína Supressora de Tumor p53/genética , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Apoptose , Proliferação de Células , Células Cultivadas , Agonistas Colinérgicos/toxicidade , Metilação de DNA , Epigênese Genética , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Nus , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Fibrose Oral Submucosa/induzido quimicamente , Fibrose Oral Submucosa/metabolismo , Regiões Promotoras Genéticas , Proteína Supressora de Tumor p53/metabolismo
18.
J Biol Chem ; 293(5): 1666-1675, 2018 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-29180450

RESUMO

It has been suggested that voltage-dependent anion channels (VDACs) control the release of superoxide from mitochondria. We have previously shown that reactive oxygen species (ROS) such as superoxide (O2̇̄) and hydrogen peroxide (H2O2) stimulate epithelial sodium channels (ENaCs) in sodium-transporting epithelial tissue, including cortical collecting duct (CCD) principal cells. Therefore, we hypothesized that VDACs could regulate ENaC by modulating cytosolic ROS levels. Herein, we find that VDAC3-knockout(KO) mice can maintain normal salt and water balance on low-salt and high-salt diets. However, on a high-salt diet for 2 weeks, VDAC3-KO mice had significantly higher systolic blood pressure than wildtype mice. Consistent with this observation, after a high-salt diet for 2 weeks, ENaC activity in VDAC3-KO mice was significantly higher than wildtype mice. EM analysis disclosed a significant morphological change of mitochondria in the CCD cells of VDAC3-KO mice compared with wildtype mice, which may have been caused by mitochondrial superoxide overload. Of note, compared with wildtype animals, ROS levels in VDAC3-KO animals fed a normal or high-salt diet were consistently and significantly increased in renal tubules. Both the ROS scavenger 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine (TEMPOL) and the mitochondrial ROS scavenger (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (mito-TEMPO) could reverse the effect of high-salt on ENaC activity and systolic blood pressure in the VDAC3-KO mice. Mito-TEMPO partially correct the morphological changes in VDAC3-KO mice. Our results suggest that knocking out mitochondrial VDAC3 increases ROS, alters renal sodium transport, and leads to hypertension.


Assuntos
Canais Epiteliais de Sódio/metabolismo , Peróxido de Hidrogênio/metabolismo , Rim/metabolismo , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/deficiência , Sódio/metabolismo , Superóxidos/metabolismo , Canais de Ânion Dependentes de Voltagem/deficiência , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/genética , Óxidos N-Cíclicos/farmacologia , Canais Epiteliais de Sódio/genética , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/patologia , Transporte de Íons/efeitos dos fármacos , Transporte de Íons/genética , Rim/patologia , Camundongos , Camundongos Knockout , Mitocôndrias/genética , Mitocôndrias/patologia , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Compostos Organofosforados/farmacologia , Piperidinas/farmacologia , Marcadores de Spin , Canais de Ânion Dependentes de Voltagem/metabolismo
19.
Int J Ophthalmol ; 10(11): 1633-1639, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29181304

RESUMO

AIM: To investigate whether DNA vaccine encoding herpes simplex virus 1 (HSV-1) glycoprotein C (gC) and glycoprotein D (gD) will achieve better protective effect against herpes simplex keratitis (HSK) than DNA vaccine encoding gD alone. METHODS: DNA vaccine expressing gD or gC combined gD (gD.gC) were constructed and carried by chitosan nanoparticle. The expression of fusion protein gD and gC were detected in DNA/nanoparticle transfected 293T cells by Western-blot. For immunization, mice were inoculated with DNA/nanoparticle for 3 times with 2wk interval, and two weeks after the final immunization, the specific immune responses and clinical degrees of primary HSK were evaluated. RESULTS: Fusion protein gD.gC could be expressed successfully in cultured 293T cells. And, pRSC-gC.gD-IL21 DNA/chitosan nanoparticle could effectively elicit strongest humoral and cellular immune response in primary HSK mice evidenced by higher levels of specific neutralizing antibody and sIgA production, enhanced cytotoxicities of splenocytes and nature killer cells (NK), when compared with those of gD alone or mocked vaccine immunized mice. As a result, gC-based vaccine immunized mice showed least HSK disease. CONCLUSION: gC-based DNA vaccine could effectively prevent the progress of primary HSK, suggesting that this DNA vaccine could be a promising vaccine for HSK treatment in the future.

20.
Oncotarget ; 8(3): 5123-5134, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-28030826

RESUMO

Recent studies indicate that the transient receptor potential canonical 6 (TRPC6) channel is highly expressed in several types of cancer cells. However, it remains unclear whether TRPC6 contributes to the malignancy of human non-small cell lung cancer (NSCLC). We used a human NSCLC A549 cell line as a model and found that pharmacological blockade or molecular knockdown of TRPC6 channel inhibited A549 cell proliferation by arresting cell cycle at the S-G2M phase and caused a significant portion of cells detached and rounded-up, but did not induce any types of cell death. Western blot and cell cycle analysis show that the detached round cells at the S-G2M phase expressed more TRPC6 than the still attached polygon cells at the G1 phase. Patch-clamp data also show that TRPC whole-cell currents in the detached cells were significantly higher than in the still attached cells. Inhibition of Ca2+-permeable TRPC6 channels significantly reduced intracellular Ca2+ in A549 cells. Interestingly, either blockade or knockdown of TRPC6 strongly reduced the invasion of this NSCLC cell line and decreased the expression of an adherent protein, fibronectin, and a tight junction protein, zonula occluden protein-1 (ZO-1). These data suggest that TRPC6-mediated elevation of intracellular Ca2+ stimulates NSCLC cell proliferation by promoting cell cycle progression and that inhibition of TRPC6 attenuates cell proliferation and invasion. Therefore, further in vivo studies may lead to a consideration of using a specific TRPC6 blocker as a complement to treat NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Imidazóis/farmacologia , Neoplasias Pulmonares/metabolismo , RNA Interferente Pequeno/farmacologia , Canal de Cátion TRPC6/antagonistas & inibidores , Células A549 , Cálcio/metabolismo , Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fibronectinas/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Invasividade Neoplásica , Proteína da Zônula de Oclusão-1/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...