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1.
Aquat Toxicol ; 271: 106937, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38728928

RESUMEN

In aquaculture around the world, sulfamonomethoxine (SMM), a long-acting antibiotic that harms microalgae, is widely employed in combination with trimethoprim (TMP), a synergist. However, their combined toxicity to microalgae under long-term exposures at environmentally relevant concentrations remains poorly understood. Therefore, we studied the effects of SMM single-exposures and co-exposures (SMM:TMP=5:1) at concentrations of 5 µg/L and 500 µg/L on Chlorella pyrenoidosa within one aquacultural drainage cycle (15 days). Photosynthetic activity and N assimilating enzyme activities were employed to evaluate microalgal nutrient assimilation. Oxidative stress and flow cytometry analysis for microalgal proliferation and death jointly revealed mechanisms of inhibition and subsequent self-adaptation. Results showed that exposures at 5 µg/L significantly inhibited microalgal nutrient assimilation and induced oxidative stress on day 7, with a recovery to levels comparable to the control by day 15. This self-adaptation and over 95 % removal of antibiotics jointly contributed to promoting microalgal growth and proliferation while reducing membrane-damaged cells. Under 500 µg/L SMM single-exposure, microalgae self-adapted to interferences on nutrient assimilation, maintaining unaffected growth and proliferation. However, over 60 % of SMM remained, leading to sustained oxidative stress and apoptosis. Remarkably, under 500 µg/L SMM-TMP co-exposure, the synergistic toxicity of SMM and TMP significantly impaired microalgal nutrient assimilation, reducing the degradation efficiency of SMM to about 20 %. Consequently, microalgal growth and proliferation were markedly inhibited, with rates of 9.15 % and 17.7 %, respectively, and a 1.36-fold increase in the proportion of cells with damaged membranes was observed. Sustained and severe oxidative stress was identified as the primary cause of these adverse effects. These findings shed light on the potential impacts of antibiotic mixtures at environmental concentrations on microalgae, facilitating responsible evaluation of the ecological risks of antibiotics in aquaculture ponds.


Asunto(s)
Microalgas , Estrés Oxidativo , Sulfamonometoxina , Trimetoprim , Contaminantes Químicos del Agua , Trimetoprim/toxicidad , Contaminantes Químicos del Agua/toxicidad , Microalgas/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Sulfamonometoxina/toxicidad , Chlorella/efectos de los fármacos , Chlorella/metabolismo , Chlorella/crecimiento & desarrollo , Nutrientes/metabolismo , Fotosíntesis/efectos de los fármacos , Antibacterianos/toxicidad
2.
Sci Total Environ ; 903: 166581, 2023 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-37634728

RESUMEN

Expanding aquaculture has generated pollutants like fishery drugs in wastewater, which affects the aquatic environments and hinders sustainable development of aquaculture. To evaluate the occurrence, mass fluxes and production factors of fishery drugs in aquaculture, full-aquaculture-cycle monitoring in finfish and crustacean wastewater was conducted in the lower Yangtze River Basin, and 28 pesticides and 15 antibiotics were detected. The results showed that individual fishery drugs varied from ppt to ppb levels. Among them, sulfonamides were dominant with a mean concentration of 105.95 ± 4.13 ng·L-1 in finfish aquacultural wastewater, and insecticides were prevailing in crustacean aquacultural wastewater with a content of 146.56 ± 0.66 ng·L-1. Since the susceptibility to finfish disease determined the aquaculture practice, there were significant differences between two types of aquacultural wastewater. Finfish aquacultural wastewater contained more drugs and reached peak earlier in rapid-growth period, yet crustacean aquacultural wastewater peaked at the harvest period, to prevent against disease. Meanwhile, higher ecological risk, especially for florfenicol, were found in finfish wastewater. With 6 production factors from Good Aquaculture Practice, the gross yield was the most influential factor of drug mass flux, explaining 98 % variance by stepwise regression. Apart from increasing concentrations of fishery drugs in wastewater, regional high-yield aquaculture also significantly impacted the corresponding mass flux. As estimated by linear regression, 1.63 tons of target drugs would be discharged by 1 Mt. aquatic products, and 7.77 tons were discharged from aquaculture in the lower Yangtze River Basin in 2021. This is the first report to quantify mass fluxes of fishery drugs and to highlight gross yield as the most influential factor, which provides guidance for the supervision and regulation of sustainable aquaculture.

3.
Chin J Nat Med ; 20(3): 161-176, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35369960

RESUMEN

Simiao Wan (SMW) is a traditional Chinese formula, including Atractylodis Rhizoma, Achyranthis Bidentatae Radix, Phellodendri Chinensis Cortex and Coicis Semen at the ratio of 1:1:2:2. It can be used to the treatment of diabetes. However, its bioactive compounds and underlying mechanism are unclear. This study aimed to screen the antilipolytic fraction from SMW and investigate its therapeutic mechanisms on hepatic insulin resistance. Different fractions of SMW were prepared by membrane separation combined with macroporous resin and their antilipolytic activities were screened in fasted mice. The effects of 60% ethanol elution (ESMW) on lipolysis were investigated in 3T3-L1 adipocytes stimulated by palmitic acid (PA) and high fat diet (HFD)-fed mice. In our study, ESMW is the bioactive fraction responsible for the antilipolytic activity of SMW and 13 compounds were characterized from ESMW by UHPLC-QTOF-MS/MS. ESMW suppressed protein kinase A (PKA)-hormone-sensitive lipase (HSL) related lipolysis and increased AMP-activated protein kinase (AMPK) phosphorylation in PA challenged 3T3-L1 adipocytes. AMPKα knockdown abolished the inhibitory effects of ESMW on IL-6 and HSL pSer-660, revealing that the antilipolytic and anti-inflammatory activities of ESMW are AMPK dependent. Furthermore, ESMW ameliorated insulin resistance and suppressed lipolysis in HFD-fed mice. It inhibited diacylglycerol accumulation in the liver and inhibited hepatic gluconeogenesis. Conditional medium collected from ESMW-treated 3T3-L1 cells ameliorated insulin action on hepatic gluconeogenesis in liver cells, demonstrating the antilipolytic activity contributed to ESMW beneficial effects on hepatic glucose production. In conclusion, ESMW, as the antilipolytic fraction of SMW, inhibited PKA-HSL related lipolysis by activating AMPK, thus inhibiting diacylglycerol (DAG) accumulation in the liver and thereby improving insulin resistance and hepatic gluconeogenesis.


Asunto(s)
Insulina , Lipólisis , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Insulina/metabolismo , Lipólisis/fisiología , Hígado/metabolismo , Ratones , Espectrometría de Masas en Tándem
4.
Environ Pollut ; 305: 119310, 2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-35430312

RESUMEN

Bacterial and fungal communities have been widely applied as bio-indicators for ecological evaluation of copper (Cu) mine pollution in river sediments. However, the response pattern of their abundant and rare sub-communities is still unknown, limiting the further development of biological diagnostics. Here, the alpha-diversity, community composition, environmental contribution and co-occurrence network of total, abundant and rare taxa for bacteria and fungi in the Jiaopingdu Cu Mine wastewater treatment plant (WWTP) were investigated through high-throughput sequencing. The results revealed different responses of microbial alpha-diversity for abundant and rare sub-communities. The abundant taxa were ubiquitous in all sediments, while rare taxa exhibited increases of species richness in polluted areas because of heterochthonous inputs of WWTP drainage. Nevertheless, the variations of community composition were consistent for bacterial and fungal abundant and rare taxa, all of which showed significant dissimilarity between control and polluted areas. Distance-decay relationship and canonical correlation analysis indicated that abundant taxa assemblies (rbacteria = -0.924, rfungi = -0.684) were more strongly driven by environmental changes than rare ones (rbacteria = -0.626, rfungi = -0.349), because abundant microbes had higher proportions of significant variations in abundance. Co-occurrence networks revealed more keystone species with high node degree and centrality among abundant taxa compared with rare ones. Moreover, bacterial abundant and rare taxa were more sensitive to Cu mine pollution than relevant fungal taxa owing to different Cu tolerance. In conclusion, among all microbial sub-communities, abundant bacteria had the highest environmental sensitivity, suggesting their important application in biological diagnosis of Cu mine pollution. Accordingly, the abundant taxa could act as "key reservoir" for future selection of specific indicator species, for example Thiobacillus, while rare taxa no longer need excessive in-depth analysis, which would greatly improve microbial diagnosis efficiency.


Asunto(s)
Microbiota , Micobioma , Bacterias , Cobre/toxicidad , Ríos
5.
Chemosphere ; 301: 134553, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35405194

RESUMEN

Owing to climate change and intensive agricultural development, freshwater bodies have been affected by increases in both CO2 levels and chemically-reduced forms of N. However, little is known about how these changes affect cyanobacterial growth and blooms. This study explored a range of light conditions (30, 80, 130, or 200 µmol photons/m2/s) wherein Microcystis aeruginosa, a widespread bloom-forming species, was exposed to different concentrations of CO2 (400 parts per million (ppm) and 1000 ppm) in a medium containing NH4+ or NO3-. The interactive effects of N sources and CO2 levels on the C/N metabolic balance and energy balance were examined to assess changes in the growth of M. aeruginosa. When the light intensity was 80 µmol photons/m2/s, elevated CO2 could reduce intracellular reactive oxygen species (ROS) in NH4+-grown M. aeruginosa. Meanwhile, cell density and chlorophyll a (Chl a) increased with increasing CO2 levels, and the increase in Chl a was significantly greater in NH4+-grown M. aeruginosa than in NO3--grown M. aeruginosa. Under light conditions of 200 µmol photons/m2/s, elevated CO2 concentration caused NO3--grown M. aeruginosa to be affected by a large amount of ROS, and the growth of NO3--grown M. aeruginosa was finally suppressed. However, NH4+-grown M. aeruginosa had a smaller amount of ROS and showed improved growth as CO2 was elevated. This difference can be attributed to the faster metabolic pathways in the NH4+ environment, which manifested in a lower accumulation of 2-oxoglutarate and fatty acids as CO2 was elevated. These findings suggest that the simultaneous increase in ammonium and CO2 in aquatic ecosystems confers cyanobacteria with greater advantages than the combination of nitrate and CO2, which may aggravate cyanobacterial blooms.


Asunto(s)
Compuestos de Amonio , Microcystis , Compuestos de Amonio/metabolismo , Dióxido de Carbono/metabolismo , Clorofila A/metabolismo , Ecosistema , Microcystis/metabolismo , Especies Reactivas de Oxígeno/metabolismo
6.
Front Public Health ; 10: 785383, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35174122

RESUMEN

BACKGROUND: The COVID-19 pandemic has been associated with significant impacts on mental health and well-being of populations worldwide. However, little is known about its significant impact on psychological aspects of vulnerable population groups such as pregnant women. Therefore, the aim of the study was to determine the psychological impact of the COVID-19 pandemic among pregnant women in mainland China. METHODS: A cross-sectional survey was performed between July and August 2020 using a modified validated 40-item questionnaire which consisted of sociodemographics, attitude, lifestyle changes and the Impact of Event Scale (IES) toward COVID-19 using snowball and convenience samplings. RESULTS: A total of 1,078 participants were included in the study. The mean age of participants was 29.4 ± 4.0 years. Overall, the mean IES of participants was 30.6 ± 12.8 (i.e., moderate-to-severe stressful impact) amidst the COVID-19 pandemic, with 63.9% of participants had an IES score ≥26. Despite increased family and social support, more than half of participants also reported increased feeling of being horrified, apprehensive and helpless. CONCLUSIONS: The COVID-19 pandemic has several psychological impacts on pregnant women. Therefore, based on these valuable data of pregnant women collected, we recommend that a thoughtful planning and time preparation by the government would definitely help to reduce the negative impacts caused by the COVID-19 pandemic and restore the quality of life among pregnant women. Further research is needed to identify vulnerable groups including pregnant women to better adapt and inform mental health interventions and policies by health authorities.


Asunto(s)
COVID-19 , Calidad de Vida , Adulto , Control de Enfermedades Transmisibles , Estudios Transversales , Femenino , Humanos , Pandemias , Embarazo , Mujeres Embarazadas/psicología , SARS-CoV-2
7.
Br J Pharmacol ; 179(5): 958-978, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33434948

RESUMEN

BACKGROUND AND PURPOSE: Ilexgenin A is a triterpenoid from ShanLv Cha with beneficial effects on metabolic homeostasis. We investigated whether ilexgenin A could inhibit hepatic de novo fatty acid synthesis via the interfering with SREBP1 maturation. EXPERIMENTAL APPROACH: The effects of Ilexgenin A on CRTC2 translocation and SREBP1 maturation were investigated in the liver of fasted mice and hepatocytes exposed to saturated fatty acids. The effect of Iilexgenin A on hepatic lipid accumulation was also observed in high-fat diet fed mice. KEY RESULTS: Sec23A and Sec31A are two subunits of COPII complex and their interaction is essential for the processing of SREBP1 maturation. Ilexgenin A activates AMPK by reducing cellular energy and preventing cytoplasmic CRTC2 to compete with Sec23A for binding to Sec31A under nutrient-rich conditions. Consequently, ilexgenin A impaired COPII-dependent SREBP1 maturation via disrupting Sec31A-Sec23A interaction, leading to the inhibition of de novo fatty acid synthesis in the liver. In contrast, mTORC1 phosphorylated Ser136 of CRTC2, facilitating the formation of Sec31A-Sec23A interaction to promote SREBP1 maturation, whereas this action was reversed by ilexgenin A in an AMPK-dependent manner. Ilexgenin A protected CRTC2 function and restrained hepatic lipogenic response in high fat diet-fed mice, providing in vivo evidence to support the beneficial effects of ilexgenin A on lipid metabolism. CONCLUSIONS AND IMPLICATIONS: Ilexgenin A activated AMPK and restrained CRTC2 to the cytoplasm to prevent SREBP1 maturation via impairing COPII function in the liver. This suggests that CRTC2 might be a potential target for pharmacological intervention to prevent hepatic lipid deposition. LINKED ARTICLES: This article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Adenilato Quinasa , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Adenilato Quinasa/metabolismo , Adenilato Quinasa/farmacología , Animales , Citoplasma/metabolismo , Ácidos Grasos/metabolismo , Lípidos , Hígado/metabolismo , Ratones , Factores de Transcripción/metabolismo , Triterpenos
8.
Environ Sci Pollut Res Int ; 28(31): 42300-42312, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33811632

RESUMEN

Bacterial communities play critical roles in biogeochemical cycles and serve as sensitive indicators of environmental fluctuation. However, the influence of mineral resource exploitation on shaping the bacterial communities in the urban river is still ambiguous. In this study, high-throughput sequencing was used to determine the spatial distribution of the sediment bacterial communities along an urban river in the famous mining city Panzhihua of China. The results showed that mineral resource exploitation had a significant impact on the urban river bacterial community structure but not on the bacterial ecological functions. Distinct families of bacteria often associated with nutrients (i.e., Comamonadaceae and Sphingomonadaceae) and metal contaminants (i.e., Rhodobacteraceae) were more predominant in the residential and mining area, respectively. Relative to dispersal dynamics, environmentally induced species sorting may primarily influence bacterial community structure. Heavy metals and sediment physicochemical properties had both similar and significant influence on shaping bacterial community structure. Among heavy metals, essential metal elements explained more rates of bacterial variation than toxic metals at moderate contaminant levels. Moreover, the bacteria with multiple metal resistances identified in culture-dependent experiments were probably not suitable for indicating heavy metal contamination in field research. Thus, several sensitive bacterial genera such as Rhodobacter, Hylemonella, and Dechloromonas were identified as potential bioindicators to monitor metals (iron and titanium) and nutrients (phosphorus and organic carbon) in the river ecosystem of the Panzhihua region. Together, these results profiled the coupling effect of urbanization and mineral resource utilization on shaping sediment bacterial communities in urban rivers.


Asunto(s)
Metales Pesados , Contaminantes Químicos del Agua , Bacterias , China , Ecosistema , Monitoreo del Ambiente , Sedimentos Geológicos , Metales Pesados/análisis , Ríos , Contaminantes Químicos del Agua/análisis
9.
Sci Total Environ ; 754: 141889, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-32920383

RESUMEN

Increasing atmospheric CO2 concentration negatively impacts aquatic ecosystems and may exacerbate the problem of undesirable cyanobacterial bloom development in freshwater ecosystems. Elevated levels of atmospheric CO2 may increase the levels of dissolved CO2 in freshwater systems, via air-water exchanges, enhancing primary production in the water and catchments. Although high CO2 levels improve cyanobacterial growth and increase cyanobacterial biomass, the impacts on their internal physiological processes can be more complex. Here, we have reviewed previous studies to evaluate the physiological responses of cyanobacteria to high concentrations of CO2. In response to high CO2 concentrations, the pressures of inorganic carbon absorption are reduced, and carbon concentration mechanisms are downregulated, affecting the intracellular metabolic processes and competitiveness of the cyanobacteria. Nitrogen and phosphorus metabolism and light utilization are closely related to CO2 assimilation, and these processes are likely to be affected by resource and energy reallocation when CO2 levels are high. Additionally, the responses of diazotrophic and toxic cyanobacteria to elevated CO2 levels were specifically reviewed. The responses of diazotrophic cyanobacteria to elevated CO2 concentrations were found to be inconsistent, probably because of differences in other factors in experimental designs. Toxic cyanobacteria tended to be superior to non-toxic strains at low levels of CO2; however, the specific effects of microcystin on the regulation require further investigation. Furthermore, the effects of increasing CO2 levels on cyanobacterial competitiveness in phytoplankton communities and nutrient cycling in aquatic ecosystems were reviewed. High CO2 concentrations may make cyanobacteria less competitive relative to other algal taxa; however, due to the complexity of natural systems and the specificity of algal species, the dominant positions of the cyanobacteria do not seems to be changed. To better understand cyanobacterial responses to elevated CO2 levels and help control cyanobacterial bloom developments, this review has identified key areas for future research.


Asunto(s)
Dióxido de Carbono , Cianobacterias , Ecosistema , Eutrofización , Nitrógeno , Fitoplancton
10.
Water Res ; 185: 116267, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32798892

RESUMEN

The effect of rising atmospheric CO2 on freshwater lakes is a subject of considerable debate. However, it is not clear how rising CO2 concentration affects cyanobacterial bloom development under potential nutrient limitation conditions and if CO2 should be taken into account in making nutrient reduction strategy. To fill the knowledge gaps, this study investigated the spatiotemporal variability in aquatic CO2 concentration (pCO2) from 2006 to 2016 in Lake Taihu, where cyanobacterial blooms often occurred from late spring to the early fall. Lake Taihu is an atmospheric CO2 source in May and November, with only 18% and 11% pCO2-undersaturated areas, respectively. During cyanobacterial bloom in August, 81% of the lake areas are pCO2-undersaturated, absorbing ~ 0.53 t C/h of atmospheric CO2. The results demonstrated that CO2 transfer across air-water interface was important in supporting cyanobacterial bloom development. Besides, Field investigation showed that the chlorophyll a level is significantly positively correlated with supersaturated pCO2 (>13.56 µmol/L) in May, but pCO2 decreases with high chlorophyll a levels in August, suggesting that cyanobacterial growth would be promoted by high pCO2 over a threshold. These observations suggested that the effect of rising atmospheric CO2 on freshwater lakes and cyanobacterial blooms should be paid attention to. Further, when the N- and P-levels are >0.3 mg/L and >0.02 mg/L, respectively, high-pCO2 conditions allow a more rapid growth rate of cyanobacteria via improved nutrient-use efficiency. Moreover, cyanobacteria afford maximum N- or P-use efficiency at lower N- or P-concentrations with high CO2 concentration. This improvement would result in an earlier bloom-maintenance phase and higher cyanobacterial biomass. In this case, nutrient reduction is more imperative under future high CO2 conditions.


Asunto(s)
Cianobacterias , Eutrofización , Biomasa , Dióxido de Carbono , China , Clorofila A , Lagos , Nitrógeno/análisis
11.
Sci Total Environ ; 691: 1144-1154, 2019 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-31466196

RESUMEN

Rising atmospheric carbon dioxide (CO2) may stimulate the proliferation of cyanobacteria. To investigate the possible physiological responses of cyanobacteria to elevated CO2 at different nutrient levels, Microcystis aeruginosa were exposed to different concentrations of CO2 (400, 1100, and 2200 ppm) under two nutrient regimes (i.e., in nutrient-rich and nutrient-poor media). The results indicated that M. aeruginosa differed in its responses to elevated atmospheric CO2 at different nutrient levels. The light utilization efficiency and photoprotection of photosystem II were improved by elevated CO2, particularly when cells were supplied with abundant nutrients. In nutrient-poor media, both total organic carbon and the polysaccharide/protein ratio of the extracellular polymeric substance increased with elevated CO2, accompanied by high cellular carbon/nitrogen ratios. Besides, cells growing with fewer nutrients were more prone to suffer intracellular acidification with elevated CO2 than those growing with abundant nutrients. Nonetheless, alkaline phosphate activity of cyanobacteria was improved by high CO2, provided that reduced pH was in the optimum range for alkaline phosphate activity. Nitrate reductase activity was inhibited by elevated CO2 regardless of nutrient levels, leading to a reduced nitrate uptake. These changes indicate that the biogeochemical cycling of nutrients would be affected by higher atmospheric CO2 conditions. Overall, cyanobacteria in eutrophic waters may benefit more than in oligotrophic waters from rising atmospheric CO2 concentrations, and evaluations of the influence of rising atmospheric CO2 on algae should account for the nutrient level of the ecosystem.


Asunto(s)
Atmósfera/química , Dióxido de Carbono/análisis , Cianobacterias/fisiología , Eutrofización
12.
IEEE Trans Image Process ; 22(7): 2521-31, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23475358

RESUMEN

Manifold learning is widely used in machine learning and pattern recognition. However, manifold learning only considers the similarity of samples belonging to the same class and ignores the within-class variation of data, which will impair the generalization and stableness of the algorithms. For this purpose, we construct an adjacency graph to model the intraclass variation that characterizes the most important properties, such as diversity of patterns, and then incorporate the diversity into the discriminant objective function for linear dimensionality reduction. Finally, we introduce the orthogonal constraint for the basis vectors and propose an orthogonal algorithm called stable orthogonal local discriminate embedding. Experimental results on several standard image databases demonstrate the effectiveness of the proposed dimensionality reduction approach.

13.
Atherosclerosis ; 174(2): 215-23, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15136051

RESUMEN

Tetrandrine (TET) is a well known naturally occurred nonspecific Ca(2+) channel blocker. It has long been used for the treatment of arrhythmia, hypertension, and occlusive cardiovascular disorders. The objective of the present study was to investigate the effect of TET on the proliferation of primary cultured rat aortic smooth muscle cells (RASMCs). TET significantly inhibited both 10% fetal bovine serum (FBS) and 50 ng/ml platelet-derived growth factor (PDGF)-BB-induced proliferation, [(3) H] ]thymidine incorporation into DNA, and p42/p44 mitogen-activated protein kinase (ERK1/2) phosphorylation at the concentration of 1.0 and 5.0 microM. Flow cytometry analysis of DNA content in synchronized cells revealed blocking of the FBS-inducible cell cycle progression by TET. In accordance with these findings, TET 5 microM caused a 48% decrease in the early elevation of c-fos expression induced after 10% FBS addition. Furthermore, in contrast to its distinguishable higher potency of Ca(2+) antagonistic activity, verapamil showed lower potent antiproliferative activities than TET. These results suggest that TET can exert antiproliferative effects against mitogenic stimuli for RASMCs in vitro by a mechanism that involves the MAPK pathway, altering cell cycle progression, and the inhibitory action cannot be limited to its Ca(2+) modulation.


Asunto(s)
Alcaloides/farmacología , Bencilisoquinolinas/farmacología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-fos/metabolismo , Análisis de Varianza , Animales , Aorta/citología , Becaplermina , Western Blotting , Ciclo Celular/efectos de los fármacos , División Celular/efectos de los fármacos , División Celular/fisiología , Células Cultivadas , ADN/biosíntesis , Activación Enzimática/efectos de los fármacos , Masculino , Proteína Quinasa 3 Activada por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/efectos de los fármacos , Músculo Liso Vascular/citología , Músculo Liso Vascular/enzimología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/fisiología , Reacción en Cadena de la Polimerasa , Probabilidad , Proteínas Proto-Oncogénicas c-sis , Ratas , Ratas Sprague-Dawley , Sensibilidad y Especificidad
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