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1.
Cell Death Dis ; 11(2): 97, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029701

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

2.
Cell Death Dis ; 11(1): 22, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924749

RESUMO

Accelerated atherosclerotic calcification is responsible for plaque burden, especially in diabetes. The regulatory mechanism for atherosclerotic calcification in diabetes is poorly characterized. Here we show that deletion of PARP-1, a main enzyme in diverse metabolic complications, attenuates diabetic atherosclerotic calcification and decreases vessel stiffening in mice through Runx2 suppression. Specifically, PARP-1 deficiency reduces diabetic arteriosclerotic calcification by regulating Stat1-mediated synthetic phenotype switching of vascular smooth muscle cells and macrophage polarization. Meanwhile, both vascular smooth muscle cells and macrophages manifested osteogenic differentiation in osteogenic media, which was attenuated by PARP-1/Stat1 inhibition. Notably, Stat1 acts as a positive transcription factor by directly binding to the promoter of Runx2 and promoting atherosclerotic calcification in diabetes. Our results identify a new function of PARP-1, in which metabolism disturbance-related stimuli activate the Runx2 expression mediated by Stat1 transcription to facilitate diabetic arteriosclerotic calcification. PARP-1 inhibition may therefore represent a useful therapy for this challenging complication.

3.
Chin J Integr Med ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31919749

RESUMO

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION: Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

4.
J Environ Manage ; 259: 110070, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31929037

RESUMO

Salt marshes are changeable and important ecosystems that currently face various threats, including global climate change and human activities. The influence of these factors can result in the degradation of salt marshes. Tidal creeks, which are an important source of nutrients and other substances for salt marsh vegetation, play an important role in the health of salt marshes. In this study, the morphological characteristics of tidal creeks and the characteristics of two typical plants, Suaeda glauca (SG) and Phragmites communis (PC), in the Yellow River Delta, China were investigated to determine the effect of tidal creeks on these plants. Aerial photography and field measurements of tidal creeks were carried out from May to July 2018 in the study area. At the same time, nine line-intercepts were set in the vertical direction of tidal creeks to investigate plants. The results showed that different grades of tidal creek exerted no significant influence on the growth of either S. glauca or P. communis. However, unlike grade, the size of a creek and the distance from it had marked effects on these plants. The cross-sectional area of a tidal creek had a significant positive impact on the density of S. glauca (r = 0.39, p = 0.02). For P. communis, the depth of a tidal creek had a strong correlation with this species' density (r = 0.51, p = 0.04) and height (r = 0.63, p = 0.01). Meanwhile, there was a negative relationship between the distance from tidal creeks and the height of S. glauca (r = -0.52, p = 0.02). Conversely, the height (r = 0 0.90, p = 0.00) and density (r = 0.62, p = 0.01) of P. communis were positively affected by its vertical distance from tidal creeks. We found that the subtidal zone near a tidal creek was more conducive to the recovery and growth of S. glauca, and that areas further away from a tidal creek, located in the intertidal and subtidal zones, were more conducive to the recovery and growth of P. communis. The parameters associated with tidal creeks in the subtidal zone (cross sectional area 4.55 m2, distance 0-10 m) were beneficial for the growth of S. glauca. For P. communis, relevant features in the intertidal and subtidal zones (depth 0.40-0.45 m, distance 20-60 m) are useful. Our results suggest that attention should be paid to the effects of size and distribution of tidal creeks during the process of salt marsh restoration. This work also provides practical guidance for the restoration of native salt marshes in China.


Assuntos
Ecossistema , Áreas Alagadas , China , Poaceae , Rios
5.
J Mol Cell Cardiol ; 139: 98-112, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31982427

RESUMO

BACKGROUND: Salvianolic acid B (Sal B) is the representative component of phenolic acids derived from the dried root and rhizome of Salvia miltiorrhiza Bge. (Labiatae), which has been widely used for the treatment of cardiovascular and cerebrovascular diseases. However, the effect of Sal B on diabetic cardiomyopathy (DCM) is still unclear. METHODS: Type 1 diabetes mellitus was induced in C57BL/6 J mice by streptozotocin (STZ) treatment, whereas meanwhile Salvianolic Acid B (Sal B (15 or 30 mg/kg/d) was intraperitoneally injected for 16 weeks. At the end of this period, cardiac function was assessed by echocardiography, and total collagen deposition was evaluated by Masson's trichrome and Picrosirius Red staining. Human umbilical vein endothelial cells exposed to hypoxia were used to investigate the effect of different doses of Sal B on angiogenesis and tube formation in vitro. Transcriptome sequencing was performed to identify potential targets of Sal B. RESULTS: Sal B ameliorated left ventricular dysfunction and remodeling, and decreased collagen deposition in the heart of diabetic mice. Administration of Sal B increased the expression of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and VEGFA in a dose-dependent manner and promoted angiogenesis both in vivo and in vitro. Furthermore, Sal B reduced HG-induced insulin-like growth factor-binding protein 3 (IGFBP3) expression, induced the phosphorylation of extracellular signal-regulated protein kinase and protein kinase B (AKT) activities, enhanced cell proliferation, and activated VEGFR2/VEGFA signaling in endothelial cells. The underlying mechanisms involve SalB that enhances IGFBP3 promoter DNA methylation and induce nuclear translocation of IGFBP3 in HUVECs under hypoxia. CONCLUSIONS: Sal B promoted angiogenesis and alleviated cardiac fibrosis and cardiac remodeling in DCM by suppressing IGFBP3.

6.
Sci Total Environ ; 702: 134889, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31733556

RESUMO

The Yellow River Delta is one of the International Important Wetlands on the west coastline of the Pacific Ocean in China. Despite its importance for regional and global ecological security, it is vulnerable because of human activities and climate change. Local government is trying to identify a more efficient way to conserve the delta thereby reducing a potential environmental crisis. The framework of hydrological connectivity provides a new perspective to study hydrological related ecological processes, while the method is highly exclusive because of environment and scale heterogeneity. This study collaborated with managers to develop a new algorithm to parameterize the hydrological connectivity on plot, point and landscape scales. Then the interspecific and conspecific structures of two dominate species (Phragmites communis and Suaeda salsa) are linked to these indices. The results show: (1) According to the point and plot scale results, AP (semi-artificial pond) and IF (intertidal flat) has the strongest hydrological connectivity followed by TM (tidal marsh). The average positive point-scale index values in AP, IF RS (river side wetland) and TM are 0.610, 0.495, 1.162 and 1.217 and the average plot-scale index values in AP, IF RS and TM are 1.53, 0.87, 0.48 0.55. At the landscape scale, index values show high collinearity with plot density and lack of hydrological significance because of low data resolution and scale effects. (2) At the individual level, P. communis and S. salsa showed a higher interspecific and conspecific competitive strength to respond to environmental stress in the weak hydrological connectivity area. (3) At the community level, in higher salinity wetland classes, biomass, plant coverage and biodiversity showed a positive linear correlation with plot-scale indices. Future study will improve the current parametrization method at the landscape scale and reveal the response of other important plant species to hydrological connectivity in this area.


Assuntos
Monitoramento Ambiental , Hidrologia , Plantas , Biodiversidade , Chenopodiaceae , China , Poaceae , Rios , Salinidade , Solo/química
7.
PeerJ ; 7: e7851, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31637124

RESUMO

With the rapid development of industry, studies on lead pollution in total suspended particulate matter (TSP) have received extensive attention. This paper analyzed the concentration and pollution sources of lead in the Cuihu Wetland in Beijing during the period of 2016-2017. The results show that the lead contents in TSP in the Cuihu Wetland were approximately equal in summer and spring, greater in winter, and greatest in autumn. The corresponding lead concentrations were 0.052, 0.053, 0.101, and 0.115 ng/m3, respectively. We compared the 206Pb/207Pb data with other materials to further understand the potential sources of atmospheric lead. The mean values of 206Pb/207Pb from spring to winter were 1.082, 1.098, 1.092, and 1.078, respectively. We found that the lead sources may be associated with coal burning, brake and tire wear, and vehicle exhaust emissions. We also calculated the enrichment factor values for the four seasons, and the values were all much greater than 10, indicating that the lead pollution is closely related to human activities.

8.
J Clin Transl Hepatol ; 7(3): 221-225, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31608213

RESUMO

Background and Aims: Genotype (GT) 1 remains the predominant hepatitis c virus (HCV) GT in Chinese patients. Over 80% of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860, which is favorable for interferon-based treatment regimens. This phase III clinical trial aimed to evaluate the efficacy and safety of the ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin regimen for 12 weeks in treatment-naïve mainland Chinese patients infected with HCV GT1 without cirrhosis. Methods: One hundred and forty-one treatment-naïve, non-cirrhotic HCV GT1 Chinese patients (age ≥18 years) were enrolled for this single-arm, multicenter, phase III MANASA study (NCT03020082). Patients received a combination of ritonavir-boosted danoprevir (100 mg/100 mg) twice a day plus subcutaneous injection of weekly pegylated-interferon α-2a (180 µg) and oral ribavirin (1000/1200 mg/day body weight <75/≥75 kg) for 12 weeks. The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment. The secondary end-points were safety outcomes, tolerability, virologic response over time and relapse rate. Results: All enrolled patients were HCV GT1-infected, and most among them (97.9%, 123/141) had the HCV GT1b subtype. Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype (87.2%, 123/141). Overall, 140 patients completed the 12-week treatment, and 97.1% (136/140) patients achieved sustained virologic response at 12 weeks (per protocol population group, 95% confidence interval: 92.9-99.2%). Only drug-related serious adverse event occurred. Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction. One patient discontinued treatment because of severe head injury in a car accident. Conclusions: The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin produced a sustained virologic response rate of 97.1% after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients, and was safe and well tolerated. Trial Registration Clinical-Trials.gov Identifier: NCT03020082.

9.
J Clin Transl Hepatol ; 7(3): 249-257, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31608217

RESUMO

Background and Aims: Data are limited on the use of pegylated-interferon alpha-2a (peg-IFNα) in Chinese patients with chronic hepatitis B virus (HBV) infection (CHB). We evaluated the effectiveness and safety of peg-IFNα in Chinese patients with hepatitis B envelope antigen-negative CHB in routine clinical practice. Methods: In this prospective, multicenter, observational, non-interventional cohort study, patients were assessed for up to 1 year after peg-IFNα treatment cessation. Treating physicians established the dosing and treatment duration according to Chinese clinical practice. Effectiveness of peg-IFNα treatment was measured by the percentage of: patients with HBV DNA <2000 IU/mL and loss of hepatitis B surface antigen (commonly known as HBsAg); HBV DNA level at end of treatment (EOT), and 6 months and 1 year posttreatment; and time course change in quantitative HBV DNA and HBsAg. Results: At EOT, 6 months posttreatment, and 1 year posttreatment, the percentage of patients with HBV DNA <2000 IU/mL was 90.0%, 81.8%, and 82.2%, and that of patients with HBsAg loss was 6.5%, 9.4%, and 9.5%, respectively. The HBV DNA level decreased from 5.61 log IU/mL at baseline to 2.48 log IU/mL at EOT and 2.67 log IU/mL at 1 year posttreatment. The HBsAg level decreased from 3.08 log IU/mL at baseline to 2.24 log IU/mL at EOT and 2.10 log IU/mL at 1 year posttreatment. The incidence of adverse events was 52.0%. Conclusions: Peg-IFNα has the potential to provide functional cure (HBsAg loss) for CHB and is well tolerated in hepatitis B envelope antigen-negative CHB patients in routine clinical practice in China. Clinical Trial Registration: ClinicalTrials.gov (NCT01730508).

10.
ACS Appl Mater Interfaces ; 11(36): 33124-33131, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31424185

RESUMO

Highly porous GaN submicron rods have been synthesized successfully by a facile hydrothermal method and heat treatment under controlled atmosphere. The morphology and size of the hydrothermal products are tailorable by adjusting the concentration of precursor solutions. Upon calcination in air, the nanorod-assembled GaOOH submicron rods are converted into bundlelike Ga2O3 and into porous GaN submicron rods under an ammonia flow. Gas-sensing characterization demonstrates that the sensors based on porous GaN exhibit high sensitivity and fast response to ethanol vapor, as well as excellent stability and reliability at high temperature. The highly porous GaN submicron rods with a large specific surface area, small grain size, and high length-to-diameter ratio show better response to ethanol. A possible sensing enhancement mechanism is also proposed. This study provides a promising route for the novel synthesis of GaN submicron rods for high-performance gas sensors.

11.
Environ Sci Pollut Res Int ; 26(28): 29041-29051, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31392615

RESUMO

As a transitional zone between aquatic and terrestrial ecosystems, the riparian buffer is an important control measure for non-point source pollution. The research presented here mainly discussed the interception efficiencies of different vegetation types for nitrogen and phosphorus pollution. The results showed that canopy, shrub, and grass interceptions basically accounted for about 80.0% of total interception, and therefore riparian buffer configurations should clearly distinguish three levels of vegetation types. (1) Canopy, shrub, grass, and litter interceptions of Pinus tabuliformis (YS) were the highest, up to about 71.1%. (2) Platycladus orientalis (CB) had the highest transportation and enrichment for the elements nitrogen (N) and phosphorus (P) throughout the process, which the value of TP decreased from 0.2 to 0.12 mg/L and the value of TN decreased from 5.0 to 2.5 mg/L. (3) The transportation of total phosphorus (TP) of the three tree species was higher than the transportation of total nitrogen (TN), showing that the enrichment of P was stronger than that of N. Thus, Pinus tabuliformis is the best configuration for rainfall interception, while Platycladus orientalis is the best configuration for N and P removals. Different forest configurations should also be considered to build a riparian buffer to remove nutrient in the future.


Assuntos
Monitoramento Ambiental , Poluição da Água/análise , Pequim , Ecossistema , Florestas , Nitrogênio/análise , Fósforo/análise , Pinus , Árvores , Água , Poluição da Água/estatística & dados numéricos
12.
Environ Sci Pollut Res Int ; 26(18): 18304-18315, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31041710

RESUMO

Litter decomposition is a complex process that is influenced by many different physical, chemical, and biological processes. Environmental variables and leaf litter quality (e.g., nutrient content) are important factors that play a significant role in regulating litter decomposition. In this study, the effects of adding fungi and using different mesh size litter bags on litter (Populus tomentosa Carr. and Salix matsudana Koidz.) decomposition rates and water quality were investigated, and investigate the combination of these factors influences leaf litter decomposition. Dissolved oxygen (DO), chemical oxygen demand (COD), total phosphorus (TP), and ammonia-nitrogen (NH3-N) were measured during the 112-day experiment. The salix leaf litter (k = 0.045) displayed faster decomposition rates than those of populous leaf litter (k = 0.026). Litter decomposition was initially slow and then accelerated; and by the end of the experiment, the decomposition rate was significantly higher (p = 0.012, p < 0.05) when fungi were added to the treatment process compared to the blank, and litter bags with different mesh sizes did not influence the decomposition rate. The variations in the decomposition rates and nutrient content were influenced by litter quality and a number of environmental factors. The decomposition rate was most influenced by internal factors related to litter quality, including the N/P and C/P ratios of the litter. By quantifying the interact effect of environment and litter nutrient dynamic, to figure out the revetment plant litter decomposition process in a wetland system in biological physical and chemical aspects, which can help us in making the variables that determine decomposition rates important for assessing wetland function.


Assuntos
Biodegradação Ambiental , Fungos/fisiologia , Folhas de Planta , Populus , Salix , Qualidade da Água , Áreas Alagadas , China , Ecossistema , Vidro , Nitrogênio/análise , Tamanho da Partícula , Fósforo/análise , Folhas de Planta/química , Microbiologia do Solo
13.
Acta Biochim Biophys Sin (Shanghai) ; 51(3): 293-300, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30883649

RESUMO

Diabetic cardiomyopathy is an important contributor to morbidity and mortality of diabetic patients by causing heart failure. Interstitial and perivascular fibrosis plays a crucial role in diabetic cardiomyopathy. However, there is a lack of effective specific treatments available for diabetic cardiomyopathy. In the present study, we aim to explore the effects of Liraglutide, a GLP-1 analogue, on diabetic cardiomyopathy in STZ-induced diabetic rats fed with high-fat diet. A total of 60 male Wistar rats were randomly assigned to three groups, i.e. normal group, model group, and Liraglutide group, with 20 rats in each group. Serum levels of TC, TG, LDL-C, NEFA, and hydroxyproline were measured using commercial kits. Cardiac function was evaluated by QRS waves, LVEDd, LVESd, and LVEF. Myocardial fibrosis was measured by immunohistochemistry. Our results demonstrated that chronic administration of Liraglutide decreased the level of blood glucose and significantly alleviated lipid metabolic disturbance compared with the model group. Furthermore, Liraglutide was found to improve the damaged cardiac function. In line with this, we also found that the alleviation of cardiac dysfunction was associated with the decreased fibrosis in diabetic myocardial tissues, which was reflected by the decreased expressions of P4hα-1, COL-1, COL-3, MMP-1, and MMP-9. Our results thus suggest that Liraglutide might have a myocardial protective effect by inhibiting P4hα-1-mediated myocardial fibrosis.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Cardiomiopatias Diabéticas/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Liraglutida/uso terapêutico , Miocárdio/patologia , Pró-Colágeno-Prolina Dioxigenase/antagonistas & inibidores , Animais , Glicemia/análise , Diabetes Mellitus Experimental/complicações , Fibrose , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Estreptozocina
14.
Sci Rep ; 9(1): 2532, 2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30796348

RESUMO

Structural hydrological connectivity has been proposed to describe the geological structure of the landscape as well as to explain hydrological behaviors. Indices based on the topological or soil condition were developed to interpret their relationships. While previous studies mainly focused on well-instrumented catchments which are narrow in humidity or temperate zone, the hydrological responses to structural connectivity at the plot and hill slope scale as well as in arid or semi-arid climate conditions remain unclear. This study was conducted in the semi-arid mountainous region of northern China in Haihe Basin which is the source of water of about 350 million people. Experiments were conducted during the rainy season in 2012 and 2013 using four runoff plots. Two indices, flow path length (FL) based on topography and integral connectivity scale length (ICSL) based on soil moisture conditions, developed to represent hydrological connectivity structure and the runoff response to rainfall were analyzed. The results showed that the surface runoff coefficient was strongly and positively linearly correlated to FL, and the correlation between subsurface flow and ICSLs was quadratic. Plots with shorter FL required more rainfall to generate surface runoff. In the shallow soil layer, when the ICSLs are relatively low, the soil can store more water and less rainfall feeds subsurface runoff. Further analysis indicated that improved shallow soil connectivity conditions might enhance the water-holding capacity and lead to lower water yields for each event. This study demonstrated that hydrological structure connectivity could explain the mechanism of runoff generation in semi-arid areas while further experiments should be undertaken to find the threshold-like relationship between FL and surface runoff as well as the influence of plant cover on hydrological behaviors.

15.
Biomed Pharmacother ; 112: 108689, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30802825

RESUMO

AIM: The aim of this study was to evaluate the antihypertensive effect of Xin Mai Jia (XMJ) and to explore the mechanism of its hypotensive effect. METHODS: A total of 50 spontaneously hypertensive rats (SHR) were randomised into five groups. A total of 30 Wistar-Kyoto rats were randomised into three groups, comprising the control group. All of the rats were administered medicine through a gastrogavage once a day for 8 weeks. The tail-cuff method was applied to their monitor blood pressure. After 8 weeks of treatment, serum NO, SOD activity, MDA level, ET, ALD, AngII, RE, and CGRP in the serum were detected in all of the rats. Pathological changes in the aorta were observed via haematoxylin-eosin (HE) and immunohistochemical staining. Vasodilation function was assessed by measuring acetylcholine-induced vessel relaxation in the rats' organ chambers. The function of the mesenteric arteries was measured using DMT wire myography. Human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVECs) injury models were induced by hydrogen peroxide (H2O2). HASMCs and HUVECs were injured by H2O2 and then exposed to various drugs. HASMC and HUVEC migration was evaluated using the cell scratch test. The expression of the AT1 receptors (AT1R) in the HASMCs was detected via immunofluorescence (IFC) assay. RESULTS: After 8 weeks of treatment, XMJ reduced the systolic blood pressure of the SHR. XMJ significantly reduced the serum RE, AngII, ALD, and ET-1 levels and increased the content of CGRP and NO in the SHR, upregulated the SOD content, and downregulated MDA level of the SHR. XMJ improved pathological damage of the aorta to varying degrees, decreased the expression of AT1R in the SHR aortic vessels, and improved the mesenteric microvascular relaxation of the SHR. Cell experiments confirmed that XMJ inhibited the migration of the HUVECs and HASMCs induced by H2O2 and the expression of AT1R in the HASMCs. CONCLUSION: XMJ had satisfactory hypotensive action on the SHR in this study. Its mechanism may be associated with inhibiting RAAS activity and improving RAAS function, inhibiting hypertensive-induced vascular diastolic dysfunction, and improving vascular endothelial function.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Hipertensão/tratamento farmacológico , Animais , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/fisiologia , Células Cultivadas , Medicamentos de Ervas Chinesas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Hipertensão/fisiopatologia , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Distribuição Aleatória , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
16.
Pflugers Arch ; 471(2): 347-355, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30353369

RESUMO

Our study explored the effects of lncRNA UCA1 on the proliferation and apoptosis in hypoxic human pulmonary artery smooth muscle cells (HPASMCs) and highlighted the endogenous relationship between UCA1, ING5, and hnRNP I in cell proliferation. Hypoxia-induced HPASMCs were used to simulate pulmonary arterial hypertension in vitro. Microarray assay was adopted to screen the dysregulated expressed lncRNAs in HPASMCs to find out the target gene of our study. And RT-qPCR was performed to detect the expression of lncRNA UCA1 under hypoxia and normoxia. After transfection, the relationship between UCA1 and cell proliferation in HPASMCs under hypoxia were determined by cell proliferation assay and relative expression of PCNA. Next, ELISA assays were conducted to measure the protein levels of PCNA and ING5. What's more, flow cytometry was employed to measure the apoptosis rate in differentially UCA1-expressed HPASMCs. RIP assays were conducted to further clarify the endogenous relationship between UCA1 and ING5 in hypoxic HPASMCs. Finally, the effects of ING5 to HPASMCs were detected after transfection of ING5 and UCA1 to figure out the role of ING5 in HPASMCs. Hypoxia was revealed to induce proliferation and inhibited apoptosis in HPASMCs. Besides, UCA1 was confirmed to be highly expressed under hypoxia compared with normoxia. UCA1 boosted cell proliferation under hypoxia in HPASMCs. However, the apoptosis was suppressed in the hypoxic HPASMCs transfected with pcDNA3.1-UCA1. Further, mechanism studies found that UCA1 competed with ING5 for hnRNP I, so that upregulating UCA1 inhibited the protein levels of ING5. And finally we found that ING5 restrained cell viability, but promoted cell apoptosis in hypoxic HPASMCs, which was reversed by UCA1 over-expression. In summary, our findings manifested that UCA1 promoted proliferation and restrained apoptosis by competing with ING5 for hnRNP I in HPASMCs induced by hypoxia, indicating their potential roles for the cure of hypoxic pulmonary hypertension.

17.
J Cell Physiol ; 234(6): 9535-9550, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30367500

RESUMO

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by the apoptosis resistance and hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Its pathogenesis has not been revealed. Here, we carried out experiments to investigate the functions of miR-140-5p and tumor necrosis factor-α (TNF-α). METHODS: We selected GSE703 from Gene Expression Omnibus (GEO) Database to conduct microarray analysis using R software and Gene Set Enrichment Analysis (GSEA). Combing bioinformatics results, the upregulation of miR-140-5p inhibited PAH progression through targeting TNF-α. RNA expression was measured by quantitative real-time polymerase chain reaction (RT-qPCR) and protein level was measured by western blot analysis and enzyme-linked immunosorbent assays (ELISA). We conducted monocrotaline (MCT) injection to rats to form PAH animal models. The lung tissues were observed by hematoxylin-eosin (HE) staining and Sirius red-picric acid staining. Right ventricular systolic pressure (RVSP) and the ratio of right ventricle (RV)-to-left ventricle (LV) plus septum (S) weight (RV/[LV + S]) were measured in MCT-induced animal models. Overexpression of miR-140-5p and TNF-α were utilized to research the proliferation, migration, and phenotypic variation of hypoxia-mediated PASMCs. The binding between miR-140-5p and TNF-α 3'-untranslated region (3'-UTR) was confirmed via luciferase reporter assay. RESULTS: Downregulation of miR-140-5p and upregulation of TNF-α were observed in PAH rat model and hypoxia-mediated PASMCs. And we proved that overexpression of miR-140-5p could suppress the proliferation, migration, and phenotypic variation of PASMCs, therefore inhibiting PAH pathogenesis. Luciferase assay verified that miR-140-5p targeted TNF-α directly. A converse correlation was also shown between miR-140-5p and TNF-α in PASMCs. CONCLUSIONS: miR-140-5p and TNF-α are important regulators in PAH pathology and may serve as a therapeutic target for PAH.

18.
J Asthma ; 56(1): 11-20, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29985082

RESUMO

OBJECTIVE: To investigate the correlations among airway inflammation, airway epithelial injury and airway hyperresponsiveness (AHR) in asthmatic mice treated with dexamethasone. METHODS: Female BALB/c mice were sensitized with intraperitoneal and hypodermic injections of ovalbumin (OVA) and aluminum on days 0, 7 and 14, challenged with OVA starting on day 21 for 10 days, and treated with dexamethasone via intraperitoneal injection starting on day 28 for 3 days. Female C57BL/6 mice were treated intranasally with house dust mite (HDM) on days 1 and 14, challenged intranasally with HDM on days 21, 23, 25, 27 and 29, and treated with sivelestat (a selective neutrophil elastase inhibitor) via intraperitoneal injection after each challenge. Following the final challenge, enhanced pause (Penh) and differential cell counts in the broncho-alveolar lavage fluid were measured and the correlations were analyzed. RESULTS: Compared with OVA-challenged BALB/c mice, the counterpart mice treated with dexamethasone showed reduced Penh and shedding of airway epithelial cells. In addition, we found that Penh 50 (an indicator of AHR) had positive correlations with airway neutrophils and shedding of airway epithelial cells, but no correlation with eosinophils, lymphocytes or macrophages. Moreover, shedding of airway epithelial cells had positive correlations with airway neutrophils, but no correlation with eosinophils, lymphocytes or macrophages. Further, sivelestat decreased Penh 50 and shed airway-epithelial cells in HDM-challenged C57BL/6 mice. CONCLUSIONS: Collectively, our findings suggest that airway neutrophils and excessive shedding of airway epithelial cells, but not eosinophils, lymphocytes or macrophages, may be involved in AHR in asthmatic mice treated with dexamethasone.


Assuntos
Anti-Inflamatórios/farmacologia , Asma/fisiopatologia , Dexametasona/farmacologia , Glicina/análogos & derivados , Neutrófilos/efeitos dos fármacos , Mucosa Respiratória/efeitos dos fármacos , Sulfonamidas/farmacologia , Animais , Líquido da Lavagem Broncoalveolar/citologia , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Feminino , Glicina/farmacologia , Inflamação/fisiopatologia , Linfócitos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ovalbumina/farmacologia , Pyroglyphidae , Mucosa Respiratória/fisiopatologia , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/fisiopatologia
19.
Mediators Inflamm ; 2019: 3013716, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32082073

RESUMO

Sepsis is a leading cause of death in patients with severe infection worldwide. Remifentanil is an ultra-short-acting, potent opioid analgesic. In the study, we aimed to investigate the role and underlying mechanism of remifentanil in lipopolysaccharide- (LPS-) induced inflammation in human aortic endothelial cells (HAECs). HAECs were pretreated with phosphate-buffered saline (PBS) or remifentanil (2.5 µM) for 30 min, then stimulated by LPS (10 µg/ml) for another 24 h. Poly(ADP-ribose) polymerase 1 (PARP-1) was inhibited by small interfering RNA (siRNA). Superoxide anion production and DNA damage were analyzed by dihydroethidium (DHE) staining and comet assay. The inducible nitric oxide synthase (iNOS), intercellular adhesion molecule 1 (ICAM-1), PARP-1, poly(ADP-ribose) (PAR), and nuclear factor-kappa B p65 (NF-κB p65) expressions were analyzed by RT-PCR or western blotting analysis. NF-κB p65 nuclear translocation was assessed by immunofluorescence. Compared with the control group, pretreatment with remifentanil significantly reduced superoxide anion production and DNA damage, with downregulation of iNOS, ICAM-1, and PARP-1 expressions as well as PAR expression. Moreover, pretreatment with PARP-1 siRNA or remifentanil inhibited LPS-induced NF-κB p65 expression and nuclear translocation. Remifentanil reduced LPS-induced inflammatory response through PARP-1/NF-κB signaling pathway. Remifentanil might be an optimal choice of analgesia in septic patients.

20.
Hypertension ; 72(5): 1189-1199, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30354818

RESUMO

Abdominal aortic aneurysm (AAA) is a common vascular degenerative disease. PARP-1 (poly[ADP-ribose] polymerase 1) is a nuclear enzyme, which plays a critical role in vascular diseases. We hypothesized that PARP-1 inhibition might have protective effects on AAA. In vivo, Ang II (angiotensin II) was continuously infused by a micropump for 28 days to induce AAA in mice. In vitro, aortic endothelial cells and smooth muscle cells were stimulated by Ang II for 24 hours. Ang II infusion increased PARP-1 expression and activity and successfully induced AAA formation partly with a hemorrhage in ApoE-/- mice. Genetic deletion of PARP-1 markedly reduced the AAA incidence, abdominal aortic diameter, macrophage infiltration, ICAM-1 (intercellular adhesion molecule 1) and VCAM-1 (vascular adhesion molecule 1) expression, and MMP (matrix metalloproteinase) expression, as well as MMP activity; but increased smooth muscle cells content and collagens expression in AAA. PARP-1 inhibition by PJ-34 also exerted a protective effect on AAA in mice. In aortic endothelial cells, Ang II-induced oxidative stress and DNA damage, resulting in increased PARP-1 expression and activity. Compared with the control, Ang II increased TNF-α (tumor necrosis factor α) and IL-6 (interleukin-6) secretions, ICAM-1 expression and THP-1 (human acute monocytic leukemia cell line) cells adhesion, while PARP-1 inhibition by siRNA reduced the inflammatory response probably through inhibition of the phosphorylation of ERK (extracellular signal-regulated kinase), NF-κB (nuclear factor-κB), and Akt signaling pathways. In smooth muscle cells, Ang II promoted cell migration, proliferation, and apoptosis, reduced collagens expression, but increased MMPs expression, while PARP-1 deletion alleviated these effects partly by reducing NF-κB-targeted MMP-9 expression. PARP-1 inhibition might be a feasible strategy for the treatment of AAA.


Assuntos
Aneurisma da Aorta Abdominal/prevenção & controle , Pressão Sanguínea/fisiologia , Poli(ADP-Ribose) Polimerase-1/metabolismo , Angiotensina II , Animais , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Colágeno/metabolismo , Citocinas/metabolismo , Dano ao DNA/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Camundongos , Camundongos Knockout , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Poli(ADP-Ribose) Polimerase-1/genética , RNA Interferente Pequeno , Transdução de Sinais/efeitos dos fármacos
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