Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
Mais filtros










Base de dados
Tipo de estudo
Intervalo de ano de publicação
1.
Nutr J ; 19(1): 7, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964410

RESUMO

BACKGROUND: Pregnant women, neonates, and school-age children are vulnerable to iodine deficiency. The iodine contents in the environment (drinking water and household salt for cooking) vary by geographical location in China. The aim of this study was to assess the iodine status in vulnerable groups from different geographical zones and analyze the iodine content in household salt and drinking water from these zones. METHODS: In coastal and inland regions of Zhejiang Province, China, samples of spot urine, drinking water, and household salt for cooking from both pregnant women and school-age children were determined for iodine concentration between 2017 and 2018. Thyroid-stimulating hormone (TSH) levels from neonates born between 2014 and 2015 were acquired from the Newborns Screening Information System. The iodine status of the vulnerable populations was assessed according to the criteria recommended by the World Health Organization. RESULTS: The median UIC of pregnant women was significantly lower in the coastal region (113.0 µg/L) than the inland region (134.9 µg/L; p < 0.001). The median UICs of pregnant women from these two regions were below the lower optimal iodine cutoff level of 150 µg/L. The percentage of neonates with elevated TSH (> 5 mIU/L) was significantly higher in the coastal region (15.8%) than the inland region (10.5%; p < 0.001). The percentage of neonates with elevated TSH from each region decreased within the range of mild iodine deficiency of 3-19.9%. The median UIC of the coastal school-age children was 156.0 µg/L, and the median UIC of inland children was 181.5 µg/L. Both medians fell within the recommended optimal iodine range of 100-299 µg/L. The iodine concentrations in drinking water varied from 1.0 µg/L in the inland region to 2.0 µg/L in the coastal region. The proportion of households that consumed iodized salt was lower in the coastal region (nearly 65%) than the inland region (approximately 95%). CONCLUSIONS: In these two regions with low iodine contents in drinking water, both pregnant women and neonates were iodine-deficient, although school-age children were iodine-sufficient. Urgent efforts are needed to improve the iodine status of pregnant women and neonates.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31917615

RESUMO

RATIONALE: Vascular remodeling, including smooth muscle cell hypertrophy and proliferation, is the key pathological feature of pulmonary arterial hypertension (PAH). Prostaglandin (PG) I2 analogs (baraprost, iloprost, and treprostinil) are effective in the treatment of PAH. Of note, the clinically favorable effects of treprostinil in severe PAH may be attributable to concomitant activation of PGD2 receptor subtype 1 (DP1). OBJECTIVES: To study the role of DP1 in the progression of PAH and its underlying mechanism. METHODS AND RESULTS: DP1 expression was downregulated in hypoxia-treated PASMCs and in pulmonary arteries (PAs) from rodent PAH models and idiopathic PAH patients. DP1 deletion exacerbated PA remodeling in hypoxia-induced PAH, whereas pharmacological activation or forced expression of DP1 receptor had the opposite effect in different rodent models. DP1 deficiency promoted PASMC hypertrophy and proliferation in response to hypoxia via induction of mammalian target of rapamycin complex (mTORC) 1 activity. Rapamycin, an inhibitor of mTORC1, alleviated the hypoxia-induced exacerbation of PAH in DP1-/- mice. DP1 activation facilitated raptor dissociation from mTORC1 complex and suppressed mTORC1 activity through protein kinase A (PKA)-dependent phosphorylation of raptor at Ser791. Moreover, treprostinil treatment blocked the progression of hypoxia-induced PAH in mice in part by targeting DP1 receptor. CONCLUSION: DP1 activation attenuates hypoxia-induced PA remodeling and PAH through PKA-mediated dissociation of raptor from the mTORC1 complex. These results suggest that DP1 receptor may serve as a therapeutic target for the management of PAH.

3.
Surg Laparosc Endosc Percutan Tech ; 29(6): 489-492, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31584497

RESUMO

OBJECTIVE: This study aimed to evaluate and discuss whether the transareola endoscopic surgery has similar outcome outcomes to open surgery in the treatment of papillary thyroid carcinoma (PTC). METHOD: A total of 102 patients with PTC were enrolled in this study. Among them, 53 patients were treated by transareola endoscopic surgery (endoscopic group) and 49 patients were treated by open surgery (open group). Some specific factors, including thyroglobulin (Tg), radioactive iodine uptake (RAIU), postoperative nuclide imaging in thyroid area, postoperative nuclide imaging of lymph nodes suspicious for metastasis (PNILNSM), etc. were analyzed and compared between the 2 groups. RESULTS: There were no significant differences between the 2 groups regarding body mass index (22.9±3.4 vs. 24.0±3.3, P=0.103), operation time (173.3±43.2 vs. 158.8±47.9 min, P=0.110), intraoperative blood loss (41.8±19.4 vs. 35.8±31.0 mL, P=0.251, P=0.251), tumor diameter (19.0±6.8 vs. 20.2±7.2 mm, P=0.400), and overall complications (11.3% vs. 10.2%, P=0.868). No significant difference was found in the specific factors between the 2 groups concerning RAIU-2h/24h (2.44±1.34 vs. 2.58±1.65%/2.83±3.75 vs. 2.35±3.44%, P=0.646/ P=0.506), number of dissected lymph nodes (4.4±1.4 vs. 4.6±1.5, P=0.595), Tg before radioiodine therapy (4.46±5.50 vs. 5.60±8.36; P=0.495), Tg after radioiodine therapy (1.03±1.93 vs. 1.11±1.61, P=0.812, P=0.812), postoperative nuclide imaging in thyroid area (1.76±1.50 vs. 2.19±1.85 cm, P=0.195), PNILNSM before radioiodine (none: 79.2% vs. 83.7%, P=0.566; central: 17.0% vs. 12.2%, P=0.653; lateral: 1.9% vs. 4.1%, P=0.450; central+lateral: 1.9% vs. 0%, P=1.000), and PNILNSM after radioiodine (none: 94.3% vs. 95.9%, P=0.111; central: 3.8% vs. 2.0%, P=1.000; lateral: 0 vs. 2.0%, P=0.480; central+lateral: 1.9% vs. 0%, P=1.000). CONCLUSIONS: Transareola endoscopic total thyroidectomy and central lymph nodes dissection are safe and effective. According to the evaluated postoperative specific factors, this technique achieves similar outcomes to open surgery in selected patients with PTC.

4.
FASEB J ; 33(9): 10207-10217, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31216422

RESUMO

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental pollutant that causes cardiovascular toxicity. The phenotypic transformation of vascular smooth muscle cells (VSMCs) from the contractile to the synthetic phenotype is a hallmark of vascular response to injury. However, the precise role and molecular mechanism of TCDD in vascular remodeling remains unknown. In the present study, we found that TCDD treatment promoted VSMC phenotypic transition from contractile to synthetic phenotype and exaggerated vascular neointimal hyperplasia after wire injury in mice. TCDD treatment enhanced VSMC entry into cell cycle from G0/G1 phase to S and G2/M phase. The expression of cyclin D1, cyclin-dependent kinase 4 (CDK4), and its phosphorylation were coordinately increased in response to TCDD treatment. Knocking down of aryl hydrocarbon receptor (AHR) inhibited VSMC phenotypic transition induced by TCDD and promoted S/G2 phase cell cycle arrest. TCDD treatment markedly increased oncogenic c-Jun gene expression in VSMCs. ChIP assay revealed the direct binding of AHR on the promoter of c-Jun to up-regulate the mRNA expression of c-Jun. Silencing of c-Jun gene enhanced the expression of p53 and p21, whereas attenuated the expression of CDK4 and cyclin D1 leading to the decrease in the TCDD-stimulated VSMC proliferation and synthetic phenotype transition in vitro. In vivo study showed that genetic ablation of c-Jun in VSMCs restricted injury-induced neointimal hyperplasia in TCDD-treated mice. Thus, TCDD exposure exaggerated injury-induced vascular remodeling by the activation of AHR and up-regulation of the expression of its target gene c-Jun, indicating that inhibition of AHR may be a promising prevention strategy for TCDD-associated cardiovascular diseases.-Guo, S., Zhang, R., Liu, Q., Wan, Q., Wang, Y., Yu, Y., Liu, G., Shen, Y., Yu, Y., Zhang, J. 2,3,7,8-Tetrachlorodibenzo-p-dioxin promotes injury-induced vascular neointima formation in mice.

5.
Nutrients ; 11(2)2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30781393

RESUMO

BACKGROUND: Iodine deficiency in pregnant women, defined as a median urinary iodine concentration (UIC) of less than 150 µg/L, is an important public health issue. To improve their iodine intake, it is important to understand the knowledge and practices regarding iodine. METHODS: A cross-sectional investigation was conducted on 2642 pregnant women during 2016⁻2017 in Zhejiang province, China. A 3-point Likert scale questionnaire was used to record knowledge. The UIC and iodine content in household salt were determined. RESULTS: Coastal participants were iodine deficient (median UIC 127.6 µg/L) while inland participants were iodine sufficient (median UIC 151.0 µg/L). The average knowledge scores were significantly lower for the coastal participants (24.2 points vs. 25 points for the inland participants; p < 0.001). The percentage for iodized salt consumption was significantly lower for the coastal participants (88.9% vs. 96.0% for those inland; p < 0.001). A generalized linear model analysis showed that non-iodized salt consumption, coastal region, and low knowledge scores were independently associated with a low UIC. CONCLUSIONS: Comprehensive interventional strategies are needed to develop to achieve an optimal iodine status. We recommend that coastal pregnant women should take iodine supplements based on the consumption of iodized salt, and improvement of iodine-related knowledge.


Assuntos
Ingestão de Alimentos/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Iodo/deficiência , Complicações na Gravidez/psicologia , Gestantes/psicologia , Adolescente , Adulto , China , Estudos Transversais , Feminino , Humanos , Iodo/análise , Iodo/urina , Estado Nutricional , Gravidez , Complicações na Gravidez/etiologia , Complicações na Gravidez/urina , Cloreto de Sódio na Dieta/análise , Sódio na Dieta/análise , Inquéritos e Questionários , Adulto Jovem
6.
Onco Targets Ther ; 11: 7423-7427, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30425530

RESUMO

Background: PD-1 checkpoint inhibitors have shown a robust tumor response in the treatment of various cancers. Pembrolizumab is an anti-PD-1 checkpoint antibody approved for the treatment of unresectable or metastatic melanoma in more than 40 countries. Although autoimmune pneumonitis is considered a common immune-related adverse event of PD-1 inhibitors, only limited studies have assessed the development of opportunistic infections such as pulmonary tuberculosis (TB). Case presentation: A patient with metastatic melanoma whose pulmonary TB was activated after administration of pembrolizumab for melanoma is reported. Anti-TB drugs were administered, followed by pembrolizumab (2 mg/kg, repeated every 28 days), which successfully cured the TB and achieved complete response for melanoma. Conclusion: Activated pulmonary TB was observed during the administration of pembrolizumab. It was safe and effective in the current patient to combine anti-TB drugs and PD-1 inhibitors. More importantly, screening pulmonary TB before administration of PD-1 inhibitors is recommended.

7.
Mol Cell Probes ; 41: 32-38, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30170103

RESUMO

Streptococcus pyogenes (Group A Streptococcus, GAS) and Streptococcus agalactiae (Group B Streptococcus, GBS) are common pathogens that threaten public health. In this study, a double recombinase polymerase (RPA) amplification assay was developed to rapidly detect these pathogens. Specificity tests revealed that the GAS and GBS strains were positive for speB and SIP genes, respectively. In clinical samples, the double assay performed similarly to the traditional biochemical method. The limits of detection were both ≤100 copies per reaction. In tests for simulant-contaminated samples, bacterial-culture media containing 103 CFU/mL original concentrations of S. pyogenes and S. agalactiae were positive in RPA assays after incubating for 4 h. Results can be obtained at 37 °C in 20 min. To determine whether propidium monoazide (PMA) can eliminate the influence of DNA extracted from dead cells, a bacterial suspension was treated with PMA before DNA extraction. Findings of RPA assay showed that DNA extracted from dead cells had no fluorescence signal. Therefore, the PMA-RPA assay is a promising technology for field tests and rapid point-of-care diagnosis.


Assuntos
Azidas/química , Propídio/análogos & derivados , Reação em Cadeia da Polimerase em Tempo Real/métodos , Recombinases/metabolismo , Streptococcus agalactiae/isolamento & purificação , Streptococcus pyogenes/isolamento & purificação , Ovos/microbiologia , Genes Bacterianos , Humanos , Carne/microbiologia , Propídio/química , Sensibilidade e Especificidade , Streptococcus agalactiae/genética , Streptococcus pyogenes/genética
8.
BMC Pregnancy Childbirth ; 18(1): 313, 2018 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-30075759

RESUMO

BACKGROUND: Zhejiang has achieved the goal of elimination of iodine deficiency disorders (IDD) via the implementation of universal salt iodization (USI) since 2011. Iodine content in household table salt decreased from the national standard (35 ppm) to the Zhejiang provincial standard (25 ppm) in 2012. It is crucial to periodically monitor iodine status in pregnant women because IDD in pregnancy have adverse effects on fetal neurodevelopment. METHODS: We carried out a cross-sectional study between April 2014 and September 2015 in the eight sentinel surveillance counties across Zhejiang Province, where IDD was previously known to be endemic. A total of 1304 pregnant women participated and provided a random spot urine sample and a household table salt sample. Urinary iodine concentration (UIC) was determined using arsenic-cerium catalytic spectrophotometry. Iodine content in salt was measured using a titration method with sodium thiosulphate. RESULTS: Overall, the median UIC of the total study population of pregnant women was 129.3 µg/L, with a higher UIC in inland (152.54 µg/L) and a lower UIC in coastal counties (107.54 µg/L). Household coverage of iodized salt was 94.6% and the rate of adequately iodized salt was 89.9%. CONCLUSIONS: Our results indicate deficient iodine status in the pregnant population of Zhejiang, according to the lower cut-off value of optimal iodine nutrition (150 µg/L) recommended by the World Health Organization. In addition to sustaining USI, more efforts are urgently needed to improve iodine intake in women during pregnancy, especially those residing in the coastal counties.


Assuntos
Deficiências Nutricionais , Desenvolvimento Fetal/efeitos dos fármacos , Iodo/deficiência , Transtornos do Neurodesenvolvimento , Complicações na Gravidez , Cloreto de Sódio na Dieta/normas , Adulto , China/epidemiologia , Estudos Transversais , Deficiências Nutricionais/diagnóstico , Deficiências Nutricionais/epidemiologia , Deficiências Nutricionais/etiologia , Deficiências Nutricionais/prevenção & controle , Feminino , Humanos , Recém-Nascido , Iodo/normas , Iodo/urina , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/prevenção & controle , Política Nutricional , Necessidades Nutricionais , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/etiologia , Complicações na Gravidez/prevenção & controle , Cloreto de Sódio na Dieta/análise , Urinálise/métodos
9.
J Exp Med ; 215(8): 2175-2195, 2018 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-29970474

RESUMO

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive pulmonary artery (PA) remodeling. T helper 2 cell (Th2) immune response is involved in PA remodeling during PAH progression. Here, we found that CRTH2 (chemoattractant receptor homologous molecule expressed on Th2 cell) expression was up-regulated in circulating CD3+CD4+ T cells in patients with idiopathic PAH and in rodent PAH models. CRTH2 disruption dramatically ameliorated PA remodeling and pulmonary hypertension in different PAH mouse models. CRTH2 deficiency suppressed Th2 activation, including IL-4 and IL-13 secretion. Both CRTH2+/+ bone marrow reconstitution and CRTH2+/+ CD4+ T cell adoptive transfer deteriorated hypoxia + ovalbumin-induced PAH in CRTH2-/- mice, which was reversed by dual neutralization of IL-4 and IL-13. CRTH2 inhibition alleviated established PAH in mice by repressing Th2 activity. In culture, CRTH2 activation in Th2 cells promoted pulmonary arterial smooth muscle cell proliferation through activation of STAT6. These results demonstrate the critical role of CRTH2-mediated Th2 response in PAH pathogenesis and highlight the CRTH2 receptor as a potential therapeutic target for PAH.


Assuntos
Hipertensão Pulmonar/imunologia , Ativação Linfocitária/imunologia , Receptores Imunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Células Th2/imunologia , Transferência Adotiva , Adulto , Animais , Anticorpos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Proliferação de Células/efeitos dos fármacos , Quimera , Doença Crônica , Modelos Animais de Doenças , Feminino , Deleção de Genes , Humanos , Hipertensão Pulmonar/fisiopatologia , Hipóxia/complicações , Hipóxia/fisiopatologia , Imunidade/efeitos dos fármacos , Indóis , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Camundongos , Ovalbumina , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Pirróis , Receptores Imunológicos/deficiência , Receptores de Prostaglandina/deficiência , Fator de Transcrição STAT6/metabolismo , Regulação para Cima/efeitos dos fármacos
10.
Sci Rep ; 8(1): 8835, 2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29892022

RESUMO

Zhejiang introduced universal salt iodization (USI) programme in 1995 and has achieved the goal of elimination of iodine deficiency disorders (IDD) since 2011. However, no systematical data of iodine nutritional status in population in pregnancy is available. In this cross-sectional study, pregnant women were interviewed to complete questionnaires in addition to handing in samples of urine and household table salt between March 2016 to February 2017. Date of birth, age of pregnancy, ethnicity and dietary iodine habits were recorded. The overall median urinary iodine concentration in 8561 pregnant women was 130.47 µg/L, which was lower than the cut-off value of iodine sufficiency of 150 µg/L recommended by the WHO. Participants using non-iodized salt, taking non-iodine-containing supplements, in coastal and in Han group were independently associated with iodine deficiency. The current USI programme did not supply Zhejiang pregnant women with sufficient iodine intake. They are generally iodine deficient, which have great public health importance since even mild IDD in pregnancy have adverse effects on fetal neurodevelopment. We strongly recommend urgent measures to improve iodine intake in pregnancy.


Assuntos
Iodo/deficiência , Desnutrição/epidemiologia , Complicações na Gravidez/epidemiologia , Oligoelementos/deficiência , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Iodo/administração & dosagem , Iodo/urina , Gravidez , Cloreto de Sódio na Dieta/administração & dosagem , Inquéritos e Questionários , Urina/química
11.
J Colloid Interface Sci ; 526: 28-34, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29715612

RESUMO

High-efficiency removal of chloramphenicol (CAP) drug from waste water still faces a large challenge up to date. Herein, we report the first metal-organic framework-based adsorbent (PCN-222) for CAP and effective removal was achieved. PCN-222 exhibits a large adsorption capacity of 370 mg g-1, superior to some other MOFs and various reported adsorbents; and more importantly, the adsorption equilibrium can be quickly obtained at only 58 s. Besides, ∼99.0% of CAP can be removed from water in the low concentrations (including the concentrations found in real water). Further investigation indicates that H-bond interaction, electrostatic interaction and the special pore structure of PCN-222 all play important effects on the high-efficiency removal of CAP. Therefore, our work may provide a novel perspective for removing CAP or other antibiotic drugs from contaminated water.

12.
Diabetes ; 67(9): 1748-1760, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29773555

RESUMO

Gluconeogenesis is drastically increased in patients with type 2 diabetes and accounts for increased fasting plasma glucose concentrations. Circulating levels of prostaglandin (PG) F2α are also markedly elevated in diabetes; however, whether and how PGF2α regulates hepatic glucose metabolism remain unknown. Here, we demonstrated that PGF2α receptor (F-prostanoid receptor [FP]) was upregulated in the livers of mice upon fasting- and diabetic stress. Hepatic deletion of the FP receptor suppressed fasting-induced hepatic gluconeogenesis, whereas FP overexpression enhanced hepatic gluconeogenesis in mice. FP activation promoted the expression of gluconeogenic enzymes (PEPCK and glucose-6-phosphatase) in hepatocytes in a FOXO1-dependent manner. Additionally, FP coupled with Gq in hepatocytes to elicit Ca2+ release, which activated Ca2+/calmodulin-activated protein kinase IIγ (CaMKIIγ) to increase FOXO1 phosphorylation and subsequently accelerate its nuclear translocation. Blockage of p38 disrupted CaMKIIγ-induced FOXO1 nuclear translocation and abrogated FP-mediated hepatic gluconeogenesis in mice. Moreover, knockdown of hepatic FP receptor improved insulin sensitivity and glucose homeostasis in ob/ob mice. FP-mediated hepatic gluconeogenesis via the CaMKIIγ/p38/FOXO1 signaling pathway, indicating that the FP receptor might be a promising therapeutic target for type 2 diabetes.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Dinoprosta/metabolismo , Proteína Forkhead Box O1/metabolismo , Gluconeogênese , Fígado/metabolismo , Obesidade/metabolismo , Receptores de Prostaglandina/agonistas , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/química , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Células Cultivadas , Cruzamentos Genéticos , Dieta Hiperlipídica/efeitos adversos , Jejum/metabolismo , Proteína Forkhead Box O1/agonistas , Proteína Forkhead Box O1/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Gluconeogênese/efeitos dos fármacos , Humanos , Resistência à Insulina , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos Endogâmicos C57BL , Camundongos Obesos , Camundongos Transgênicos , Obesidade/etiologia , Obesidade/patologia , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , Receptores de Prostaglandina/antagonistas & inibidores , Receptores de Prostaglandina/genética , Receptores de Prostaglandina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
EMBO Mol Med ; 10(3)2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29335338

RESUMO

Apoptotic death of cardiac myocytes is associated with ischemic heart disease and chemotherapy-induced cardiomyopathy. Chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) is highly expressed in the heart. However, its specific role in ischemic cardiomyopathy is not fully understood. Here, we demonstrated that CRTH2 disruption markedly improved cardiac recovery in mice postmyocardial infarction and doxorubicin challenge by suppressing cardiomyocyte apoptosis. Mechanistically, CRTH2 activation specifically facilitated endoplasmic reticulum (ER) stress-induced cardiomyocyte apoptosis via caspase-12-dependent pathway. Blockage of m-calpain prevented CRTH2-mediated cardiomyocyte apoptosis under ER stress by suppressing caspase-12 activity. CRTH2 was coupled with Gαq to elicit intracellular Ca2+ flux and activated m-calpain/caspase-12 cascade in cardiomyocytes. Knockdown of caspase-4, an alternative to caspase-12 in humans, markedly alleviated CRHT2 activation-induced apoptosis in human cardiomyocyte response to anoxia. Our findings revealed an unexpected role of CRTH2 in promoting ER stress-induced cardiomyocyte apoptosis, suggesting that CRTH2 inhibition has therapeutic potential for ischemic cardiomyopathy.


Assuntos
Apoptose , Calpaína/metabolismo , Estresse do Retículo Endoplasmático , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Receptores Imunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Medula Óssea/patologia , Cálcio/metabolismo , Cardiotônicos/farmacologia , Caspase 12/metabolismo , Hipóxia Celular/efeitos dos fármacos , Reprogramação Celular/genética , Doxorrubicina/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Deleção de Genes , Humanos , Masculino , Camundongos , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Prostaglandina D2/metabolismo , Regeneração/efeitos dos fármacos , Tetrazóis/farmacologia
14.
J Colloid Interface Sci ; 514: 234-239, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29274554

RESUMO

The porous metal-organic frameworks, MIL-101, MIL-101-SO3H and MIL-101-NH2 were used for the removal of harmful drug (rocephin) from water via adsorption. The kinetics study suggests that the adsorption onto all the MOFs follows the pseudo-second-order model. The adsorption isotherms results suggest that the adsorption onto MIL-101 and MIL-101-NH2 fits well with Langmuir model and the maximum adsorption capacities are calculated to 204.08 mg g-1 and 277.78 mg g-1, respectively; while the adsorption onto MIL-101-SO3H cannot fit well with both Langmuir and Freundlich models and the maximum adsorption capacity in the experiment is 25 mg g-1. Furthermore, the effect of pH as well as the adsorption mechanism was analysed systematically. It was found that electrostatic interaction as well as hydrogen-bond interaction plays dominant roles in adsorption of rocephin, and MIL-101-NH2 with abundant amino groups can exhibit better adsorption capacity and removal percentage towards rocephin than MIL-101, MIL-101-SO3H, and some other common adsorbents. In addition, co-existed Zn(NO3)2 can induce a large improvement of rocephin adsorption performance of MIL-101-NH2. At last, MIL-101-NH2 demonstrates to be a renewable adsorbent. In conclusion, we suggest MIL-101-NH2 is a promising adsorbent for effective removal of rocephin in water.

15.
J Mol Model ; 23(5): 170, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28451882

RESUMO

Metal-coordinated nitrogen-doped carbons are highly active in promoting electrochemical oxygen reduction reactions (ORR). The detailed kinetic and thermodynamic ORR behavior on three different FeN2-graphene [FeN2-G (A), (B) and (C)] structures was investigated in this work. The results show that formation of these FeN2-G configurations is energetically favorable; however, not all of them are effective for ORR. The higher HOMO energy and smaller HOMO-LUMO gap of FeN2-G (A) and (C) make them have strong adsorption strengths to ORR intermediates, which leads to occupation the active sites on the catalysts during ORR, and thus loss of catalytic activity. Examination of the results of ∆G of each reduction step also drew the same conclusion. The ∆G of the elementary steps of the ORR at zero electrode potential vs. standard hydrogen electrode are downhill only on FeN2-G (B). Throughout the entire four-electron ORR, the reduction of O to OH displays the highest reaction barrier. When the potential is >0.19 V, the reduction of OH species into water is uphill. Therefore, ORR activity is limited by two rate-determining steps on FeN2-G (B) at high potential: O and OH reduction steps.

16.
EMBO Mol Med ; 9(5): 571-588, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28341703

RESUMO

Niacin, as an antidyslipidemic drug, elicits a strong flushing response by release of prostaglandin (PG) D2 However, whether niacin is beneficial for inflammatory bowel disease (IBD) remains unclear. Here, we observed niacin administration-enhanced PGD2 production in colon tissues in dextran sulfate sodium (DSS)-challenged mice, and protected mice against DSS or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in D prostanoid receptor 1 (DP1)-dependent manner. Specific ablation of DP1 receptor in vascular endothelial cells, colonic epithelium, and myeloid cells augmented DSS/TNBS-induced colitis in mice through increasing vascular permeability, promoting apoptosis of epithelial cells, and stimulating pro-inflammatory cytokine secretion of macrophages, respectively. Niacin treatment improved vascular permeability, reduced apoptotic epithelial cells, promoted epithelial cell update, and suppressed pro-inflammatory gene expression of macrophages. Moreover, treatment with niacin-containing retention enema effectively promoted UC clinical remission and mucosal healing in patients with moderately active disease. Therefore, niacin displayed multiple beneficial effects on DSS/TNBS-induced colitis in mice by activation of PGD2/DP1 axis. The potential efficacy of niacin in management of IBD warrants further investigation.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Niacina/uso terapêutico , Prostaglandina D2/imunologia , Receptores de Prostaglandina/imunologia , Complexo Vitamínico B/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Permeabilidade Capilar/efeitos dos fármacos , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Prostaglandina D2/análise , Receptores de Prostaglandina/análise
17.
Artigo em Inglês | MEDLINE | ID: mdl-28230748

RESUMO

Universal salt iodization (USI) has been implemented for two decades in China. It is crucial to periodically monitor iodine status in the most vulnerable population, such as pregnant women. A cross-sectional study was carried out in an evidence-proved iodine-sufficient province to evaluate iodine intake in pregnancy. According to the WHO/UNICEF/ICCIDD recommendation criteria of adequate iodine intake in pregnancy (150-249 µg/L), the median urinary iodine concentration (UIC) of the total 8159 recruited pregnant women was 147.5 µg/L, which indicated pregnant women had iodine deficiency at the province level. Overall, 51.0% of the total study participants had iodine deficiency with a UIC < 150 µg/L and only 32.9% of them had adequate iodine. Participants living in coastal areas had iodine deficiency with a median UIC of 130.1 µg/L, while those in inland areas had marginally adequate iodine intake with a median UIC of 158.1 µg/L (p < 0.001). Among the total study participants, 450 pregnant women consuming non-iodized salt had mild-moderate iodine deficiency with a median UIC of 99.6 µg/L; 7363 pregnant women consuming adequately iodized salt had a lightly statistically higher median UIC of 151.9 µg/L, compared with the recommended adequate level by the WHO/UNICEF/ICCIDD (p < 0.001). Consuming adequately iodized salt seemed to lightly increase the median UIC level, but it may not be enough to correct iodine nutrition status to an optimum level as recommended by the WHO/UNICEF/ICCIDD. We therefore suggest that, besides strengthening USI policy, additional interventive measure may be needed to improve iodine intake in pregnancy.


Assuntos
Iodo/deficiência , Complicações na Gravidez/epidemiologia , Cloreto de Sódio na Dieta/administração & dosagem , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Iodo/administração & dosagem , Iodo/sangue , Iodo/urina , Estado Nutricional , Gravidez , Características de Residência , Adulto Jovem
18.
Hepatology ; 65(3): 999-1014, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28039934

RESUMO

Prostaglandin E2 (PGE2 ) is an important lipid mediator of inflammation. However, whether and how PGE2 regulates hepatic cholesterol metabolism remains unknown. We found that expression of the PGE2 receptor, E prostanoid receptor 3 (EP3) expression is remarkably increased in hepatocytes in response to hyperlipidemic stress. Hepatocyte-specific deletion of EP3 receptor (EP3hep-/- ) results in hypercholesterolemia and augments diet-induced atherosclerosis in low-density lipoprotein receptor knockout (Ldlr-/- ) mice. Cholesterol 7α-hydroxylase (CYP7A1) is down-regulated in livers of EP3hep-/- Ldlr-/- mice, leading to suppressed hepatic bile acid (BA) biosynthesis. Mechanistically, hepatic-EP3 deficiency suppresses CYP7A1 expression by elevating protein kinase A (PKA)-dependent Ser143 phosphorylation of hepatocyte nuclear receptor 4α (HNF4α). Disruption of the PKA-HNF4α interaction and BA sequestration rescue impaired BA excretion and ameliorated atherosclerosis in EP3hep-/- Ldlr-/- mice. CONCLUSION: Our results demonstrated an unexpected role of proinflammatory mediator PGE2 in improving hepatic cholesterol metabolism through activation of the EP3-mediated PKA/HNF4α/CYP7A1 pathway, indicating that inhibition of this pathway may be a novel therapeutic strategy for dyslipidemia and atherosclerosis. (Hepatology 2017;65:999-1014).


Assuntos
Aterosclerose/metabolismo , Colesterol 7-alfa-Hidroxilase/genética , Dinoprostona/metabolismo , Fator 4 Nuclear de Hepatócito/metabolismo , Receptores de Prostaglandina E Subtipo EP3/metabolismo , Animais , Aterosclerose/patologia , Células Cultivadas , Colesterol 7-alfa-Hidroxilase/metabolismo , Dieta Ocidental , Modelos Animais de Doenças , Regulação Enzimológica da Expressão Gênica , Hepatócitos/metabolismo , Metabolismo dos Lipídeos/fisiologia , Lipoproteínas LDL/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fosforilação/genética , Distribuição Aleatória , Sensibilidade e Especificidade
19.
Circ Res ; 118(8): 1194-207, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26957525

RESUMO

RATIONALE: Autologous adipose-derived stromal cells (ASCs) offer great promise as angiogenic cell therapy for ischemic diseases. Because of their limited self-renewal capacity and pluripotentiality, the therapeutic efficacy of ASCs is still relatively low. Thromboxane has been shown to play an important role in the maintenance of vascular homeostasis. However, little is known about the effects of thromboxane on ASC-mediated angiogenesis. OBJECTIVE: To explore the role of the thromboxane-prostanoid receptor (TP) in mediating the angiogenic capacity of ASCs in vivo. METHODS AND RESULTS: ASCs were prepared from mouse epididymal fat pads and induced to differentiate into endothelial cells (ECs) by vascular endothelial growth factor. Cyclooxygenase-2 expression, thromboxane production, and TP expression were upregulated in ASCs on vascular endothelial growth factor treatment. Genetic deletion or pharmacological inhibition of TP in mouse or human ASCs accelerated EC differentiation and increased tube formation in vitro, enhanced angiogenesis in in vivo Matrigel plugs and ischemic mouse hindlimbs. TP deficiency resulted in a significant cellular accumulation of ß-catenin by suppression of calpain-mediated degradation in ASCs. Knockdown of ß-catenin completely abrogated the enhanced EC differentiation of TP-deficient ASCs, whereas inhibition of calpain reversed the suppressed angiogenic capacity of TP re-expressed ASCs. Moreover, TP was coupled with Gαq to induce calpain-mediated suppression of ß-catenin signaling through calcium influx in ASCs. CONCLUSION: Thromboxane restrained EC differentiation of ASCs through TP-mediated repression of the calpain-dependent ß-catenin signaling pathway. These results indicate that TP inhibition could be a promising strategy for therapy utilizing ASCs in the treatment of ischemic diseases.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Diferenciação Celular/fisiologia , Células Endoteliais/metabolismo , Receptores de Tromboxano A2 e Prostaglandina H2/biossíntese , Tromboxanos/biossíntese , Adipócitos/efeitos dos fármacos , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , beta Catenina/biossíntese
20.
Arterioscler Thromb Vasc Biol ; 35(7): 1687-95, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25977569

RESUMO

OBJECTIVE: To investigate whether rs12731181 (A→G) interrupted miR-590-3p-mediated suppression of the prostaglandin F2α receptor (FP) and whether it is associated with essential hypertension in the Chinese population. APPROACH AND RESULTS: We found that miR-590-3p regulates human FP gene expression by binding to its 3'-untranslated region. rs12731181 (A→G) altered the binding affinity between miR-590-3p and its FP 3'-untranslated region target, thus reducing the suppression of FP expression, which, in turn, enhanced FP receptor-mediated contractility of vascular smooth muscle cells. Overexpression of FP augmented vascular tone and elevated blood pressure in mice. An association study was performed to analyze the relationship between the FP gene and essential hypertension in the Han Chinese population. The results indicated that the rs12731181 G allele was associated with susceptibility to essential hypertension. Carriers of the AG genotype exhibited significantly higher blood pressure than those of the AA genotype. FP gene expression was significantly higher in human peripheral leukocytes from individuals with the AG genotype than that in leukocytes from individuals with the AA genotype. CONCLUSIONS: rs12731181 in the seed region of the miR-590-3p target site is associated with increased risk of essential hypertension and represents a new paradigm for FP involvement in blood pressure regulation.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Hipertensão/genética , MicroRNAs/genética , Receptores de Prostaglandina/genética , Regiões 3' não Traduzidas , Animais , Sítios de Ligação , China/etnologia , Hipertensão Essencial , Predisposição Genética para Doença , Humanos , Camundongos , Polimorfismo de Nucleotídeo Único , Transcrição Genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA