Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biomed Res Int ; 2020: 2461079, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32382538

RESUMO

Ischemic cerebral stroke is a severe neurodegenerative disease with high mortality. Ischemia and reperfusion injury plays a fundamental role in ischemic cerebral stroke. To date, the strategy for ischemic cerebral stroke treatment is limited. In the present study, we aimed to investigate the effect of kaempferol (KFL), a natural flavonol, on cell injury induced by oxygen and glucose deprivation (OGD) and reoxygenation (OGD-reoxygenation) in PC12 cells. We found that KFL inhibited OGD-induced decrease of cell viability and the increase of lactate dehydrogenase (LDH) release. OGD-induced activation of mitochondrial dysfunction, mitochondrial apoptotic pathway, and apoptosis was inhibited by KFL. KFL also reduced OGD-induced oxidative stress in PC12 cells. P66shc expression and acetylation were increased by OGD and KFL inhibited these changes. Upregulation of P66shc suppressed KFL-induced decrease of apoptosis, the decrease of LDH release, and the increase of cell viability. Furthermore, KFL inhibited OGD-induced decrease of sirtuin 1 (SIRT1) expression and downregulation of SIRT1 blocked KFL-induced decrease of apoptosis, the decrease of LDH release, and the increase of cell viability. In summary, we identified that KFL exhibited a beneficial effect against OGD-induced cytotoxicity in an ischemia/reperfusion injury cell model. The findings suggest that KFL may be a promising choice for the intervention of ischemic stroke and highlighted the SIRT1/P66shc signaling.

2.
Lipids Health Dis ; 19(1): 48, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32178680

RESUMO

BACKGROUND: Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a novel inflammatory marker that has been used to predict various inflammation-related diseases. This study aims to explore the association between MHR and prevalent hyperuricemia in a rural Chinese population. METHODS: 8163 eligible participants (mean age: 54.13 years, males: 45.71%) from northeast China were enrolled in this cross-sectional study between 2012 to 2013. MHR was determined as blood monocyte count ratio to high-density lipoprotein cholesterol concentration. RESULTS: The prevalence of hyperuricemia was 12.86%. After adjusting for potential confounding factors, per SD increase of MHR caused a 25.2% additional risk for hyperuricemia, and the top quartile of MHR had an 82.9% increased risk for hyperuricemia compared with the bottom quartile. Additionally, smooth curve fitting and subgroup analyses showed a linear and robust association between MHR and prevalent hyperuricemia respectively. Finally, after introducing MHR into the established model of risk factors, the AUC displayed a significant improvement (0.718 vs 0.724, p = 0.008). Furthermore, Category-free net reclassification improvement (0.160, 95% CI: 0.096-0.224, P < 0.001) and integrated discrimination improvement (0.003, 95% CI: 0.002-0.005, P < 0.001) also demonstrated significant improvements. CONCLUSIONS: The present study suggests that MHR was positively and independently correlated with prevalent hyperuricemia among rural Chinese adults. Our results also implicate an important value for MHR in optimizing the risk stratification of hyperuricemia.

3.
Cell Death Differ ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907393

RESUMO

Osteoporosis develops because of impaired bone formation and/or excessive bone resorption. Several pharmacological treatment of osteoporosis has been developed; however, new treatments are still necessary. Cholesterol and estrogen receptor-related receptor alpha (ERRα) promote osteoclasts formation, survival, and cellular fusion and thus become high risk factors of osteoporosis. In this study, we identified that carnosic acid (CA) suppressed bone loss by dual-targeting of sterol regulatory element-binding protein 2 (SREBP2, a major regulator that regulates cholesterol synthesis) and ERRα. Mechanistically, CA reduced nuclear localization of mature SREBP2 and suppressed de novo biogenesis of cholesterol. CA subsequently decreased the interaction between ERRα and peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1ß), resulting in decreased the transcription activity of ERRα and its target genes expression. Meanwhile, CA directly bound to the ligand-binding domain of ERRα and significantly promoted its ubiquitination and proteasomal degradation. Subsequently, STUB1 was identified as the E3 ligase of ERRα. The lysine residues (K51 and K68) are essential for ubiquitination and proteasomal degradation of ERRα by CA. In conclusion, CA dually targets SREBP2 and ERRα, thus inhibits the RANKL-induced osteoclast formation and improves OVX-induced bone loss. CA may serve as a lead compound for pharmacological control of osteoporosis.

4.
Lipids Health Dis ; 18(1): 127, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31142338

RESUMO

BACKGROUND: Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a recently emerged measure of inflammation and oxidative stress and has been used to predict multiple cardiovascular abnormalities, but data relative to ischemic stroke are lacking. The goal of this study was to estimate the associations of MHR and prevalent ischemic stroke among a large cohort of general Chinese population. METHOD: The study analyzed 8148 individuals (mean age: 54.1 years; 45.7% males) enrolled in a cross-sectional population-based Northeast China Rural Cardiovascular Health Study (NCRCHS). We identified 194 patients admitted from January and August 2013 with ischemic stroke. RESULTS: After adjustment for age, sex, and potential confounders, each standard deviation (SD) increment of MHR was predictive to a greater odd of ischemic stroke (odds ratio, 1.276; 95% confidence interval [CI], 1.082-1.504), with subjects in the highest quartile of MHR levels having a 1.6-fold higher risk of prevalent ischemic stroke (95% CI, 1.045-2.524) as compared with those in the lowest quartile. Moreover, smoothing curve showed a linear positive pattern of this association. The area under the curve (AUC) significantly increased (P = 0.042) to 0.808 (95% CI, 0.779-0.837) when the combined MHR was added to the baseline logistic regression model with ischemic stroke risk factors. Also, MHR (0.004) significantly improved integrated discrimination improvement when added to the baseline model. CONCLUSIONS: The present study demonstrated for the first time a linear relation between MHR levels and the odds of ischemic stroke in a large community-based population. The MHR, a marker of high atherosclerotic burden, demonstrated incremental predictive value over traditional clinical risk factors, thus providing clinical utility in risk stratification in subjects presenting with ischemic stroke. These findings had implications for strategies aimed at lowering MHR to prevent adverse cardiovascular and cerebrovascular outcomes.


Assuntos
Isquemia Encefálica/sangue , Inflamação/sangue , Lipoproteínas HDL/sangue , Acidente Vascular Cerebral/sangue , Idoso , Biomarcadores/sangue , Isquemia Encefálica/patologia , China/epidemiologia , HDL-Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Inflamação/epidemiologia , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/patologia
5.
Eur J Pharmacol ; 850: 23-34, 2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-30716311

RESUMO

Despite the massive efforts to develop the treatment of pancreatic cancers, no effective application exhibits satisfactory clinical outcome. Macropinocytosis plays a critical role for continuous proliferation of pancreatic ductal adenocarcinoma (PDAC). In this study, we generated a screening method and identified phellodendrine chloride (PC) as a potential macropinocytosis inhibitor. PC significantly inhibited the viability of KRAS mutant pancreatic cancer cells (PANC-1 and MiaPaCa-2) in a dose-dependent manner; however, it did not affect the wild type KRAS pancreatic cancer cells (BxPC-3). Further experiments indicated that PC reduced the growth of PANC-1 cells through inhibition of macropinocytosis and diminishing the intracellular glutamine level. Disruption of glutamine metabolism led to enhance the reactive oxygen species level and induce mitochondrial membrane potential depolarization in PANC-1 cells. PC treatment caused increased Bax and decreased Bcl-2 expression, along with the activation of cleaved caspase-3, 7, 9 and cleaved-PARP, thus induced mitochondrial apoptosis. Moreover, PC inhibited macropinocytosis in vivo and effectively reduced the growth of PANC-1 xenograft tumors. All together, we demonstrated that inhibition of macropinocytosis might be an effective strategy to treat pancreatic cancers. Thus, PC could be a potential compound with improved therapeutic efficacy in patients with pancreatic cancers.


Assuntos
Mutação , Nutrientes/metabolismo , Neoplasias Pancreáticas/patologia , Pinocitose/efeitos dos fármacos , Proteínas Proto-Oncogênicas p21(ras)/genética , Quinolizinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Glutamina/metabolismo , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Eur J Pharmacol ; 809: 156-162, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28501578

RESUMO

Nowadays, more and more attention has been paid to osteoporosis caused by diabetes mellitus. Elevated levels of pro-inflammatory cytokines in diabetic patients activate the activity of osteoclasts through the RANKL/OPG pathway. The nuclear transcription factor SREBP2, a master regulator of cholesterol metabolism, has been found involved in osteoclastogenesis. In our previous study, we have identified anhydroicaritin as a potent inhibitor of transcription factor SREBPs, which improves dyslipidemia and insulin resistance. In this study, we demonstrated that anhydroicaritin could also decrease the level of SREBP2 and its target genes in osteoclasts induced by RANKL without significant cytotoxicity. Moreover, anhydroicaritin suppressed RANKL-induced osteoclasts differentiation. In STZ-induced diabetic mice model, we found that the osteoclasts were largely increased accompanied with deterioration of bone structure. Anhydroicaritin decreased the level of blood glucose and alleviated insulin resistance. More importantly, anhydroicaritin inhibited osteoclast differentiation and rescued diabetes-induced bone loss in vivo. In conclusion, anhydroicaritin, a potent SREBP2 inhibitor, inhibits the osteoclasts formation and improves diabetes-induced bone loss.


Assuntos
Benzopiranos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Osteoclastos/efeitos dos fármacos , Osteoporose/patologia , Ligante RANK/farmacologia , Proteínas de Ligação a Elemento Regulador de Esterol/antagonistas & inibidores , Animais , Benzopiranos/uso terapêutico , Linhagem Celular , Camundongos , Osteoclastos/citologia , Osteoclastos/patologia , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos
7.
Biochem Pharmacol ; 122: 42-61, 2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27816546

RESUMO

SREBPs play important roles in the regulation of lipid metabolism, and are closely related to the occurrence and development of many metabolic diseases. Small molecular inhibitors of SERBPs are important tools in developing efficient treatment of metabolic diseases. However, there are no listing drug targeting SREBPs. Therefore, there is an urgent need to develop highly specific small molecules that inhibit SREBPs. In this study, using a hepatocyte-based high-throughput screening, we identified anhydroicaritin (AHI) as a novel inhibitor of SREBPs. HepG2, HL-7702, and human primary hepatocytes were used to verify the effects of AHI. We explored the mechanism by which AHI blocks the binding of SCAP/SREBPs complex with Sec23α/24D via regulating LKB1/AMPK/mTOR pathway. AHI reduced liver cell lipid level by preventing de novo lipogenesis. In diet induced obese mice, AHI ameliorated obesity, insulin resistance, fatty accumulation in liver and hyperlipemia. In conclusion, AHI improves diet-induced obesity and alleviates insulin resistance by suppressing SREBPs maturation which is dependent on LKB1/AMPK/mTOR pathway. Thus, AHI can serve as a leading compound for pharmacological control of metabolic diseases.


Assuntos
Benzopiranos/farmacologia , Resistência à Insulina , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo , Adenilato Quinase/genética , Adenilato Quinase/metabolismo , Animais , Benzopiranos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Estrutura Molecular , Proteínas de Ligação a Elemento Regulador de Esterol/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
8.
Zhongguo Zhong Yao Za Zhi ; 40(1): 108-11, 2015 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-25993798

RESUMO

This study is to establish an HPLC-DAD-ELSD method for simultaneous determination of 5 flavones and saponins in Rhizoma Anemarrhenae including neo-mangiferin, mangiferin, timosaponin B II, timosaponin B III and timosaponin A III. Samples were analyzed on a Merck Purospher STAR column(4.6 mm x 250 mm, 5 µm). The mobile phase consisted of acetonitrile( A) and 0. 1% formic acid (B) with gradient elution at a flow rate of 1.0 mL · min(-1). The column temperature was set at 40 °C. The DAD detector wavelength was set at 254 nm. The ELSD conditions were as follows: the nebulizing gas flow rate was 2.0 L · min(-1) and temperature of drift tube was 105 °C. The volume was 10 µL. The five compounds were well separated with good linear correlations. The mean recoveries were between 102.0%-104.0%. This method was quick and reliable which provides a foundation for quality control of R. Anemarrhenae.


Assuntos
Anemarrhena/química , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Flavonas/análise , Saponinas/análise , Cromatografia Líquida de Alta Pressão/instrumentação , Rizoma/química
9.
Biochem Genet ; 47(3-4): 179-90, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19184407

RESUMO

The protein of the gustavus (gus) gene has a typical SOCS box domain and repeats in the splA and RyR (SPRY) domains. GUS can interact with Vasa and is necessary for the specification of germ cells. We cloned two zebrafish genes, SSB-1 and SSB-4 (SPRY domain SOCS box proteins). Phylogenetic analysis shows that zebrafish SSB-1 and SSB-4 are clustered into clades of SSB-1-like and SSB-4-like genes from other species. RT-PCR analysis of tissues revealed that zebrafish SSB-1 and -4 are expressed in the ovary and testis. We investigated the spatial expression patterns of zebrafish SSB-1 and -4 in embryos from the two-cell stage to 72 h postfertilization (hpf) using whole-mount in situ hybridization. SSB-1 and -4 transcripts were present in all blastomeres during the early embryonic stages, but the genes differ in their expression pattern. SSB-4 mRNA was located in the region of the primordial germ cells in 24 and 72 hpf embryos, but SSB-1 mRNA was not detected at these stages. We hypothesize that SSB-4 plays a role in the early development of germ cells.


Assuntos
Proteínas Supressoras da Sinalização de Citocina/genética , Peixe-Zebra/genética , Animais , Clonagem Molecular , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Células HeLa , Humanos , Masculino , Ovário/embriologia , Ovário/metabolismo , Filogenia , RNA Mensageiro/metabolismo , Testículo/embriologia , Testículo/metabolismo , Distribuição Tecidual , Transfecção , Peixe-Zebra/embriologia
10.
J Phys Chem B ; 110(45): 22596-600, 2006 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-17092006

RESUMO

The equilibrium and dynamic adsorption data of H(2) and D(2) on different micro- and mesoporous adsorbents with orderly structure including 3A, 4A, 5A, Y, and 10X zeolites; carbon CMK-3; silica SBA-15; and so forth were collected. Critical effect of the nanodimension of adsorbents on the adsorption behavior of hydrogen and its isotopes is shown. The highest adsorption capacity was observed at pore size 0.7 nm, but equal or even larger isotope difference in the equilibrium adsorption was observed at larger pore sizes, whereas the largest isotope difference in the dynamic adsorption was observed at 0.5 nm. The adsorption rate of D(2) is larger than that of H(2) in microporous adsorbents, but the sequence could be switched over in mesoporous materials. Linear relationship was observed between the adsorption capacity for hydrogen and the specific surface area of adsorbents although the adsorbents are made of different material, which provides a convincing proof of the monolayer mechanism of hydrogen adsorption. The linear plot for microporous adsorbents has a larger slope than that for mesoporous adsorbents, which is attributed to the stronger adsorption potential in micropores.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA