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1.
J Pharmacol Sci ; 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-32414690

RESUMO

The optimum strategy for heart failure (HF) treatment has yet to be elucidated. This study intended to test the benefit of a combination of valsartan (VAL) and perifosine (PER), a specific AKT inhibitor, in protecting against pressure overload induced mouse HF. Mouse were subjected to aortic banding (AB) surgery to establish HF models and then were given vehicle (HF), VAL (50 mg/kg/d), PER (30 mg/kg/d) or combination of VAL and PER for 4 weeks. Mouse with sham surgery treated with VEH were used for control (VEH). VAL or PER treatment could significantly alleviate mouse heart weight, attenuate cardiac fibrosis and improve cardiac function. The combination treatment of VAL and PER presented much better benefit compared with VAL or PER group respectively. PER treatment significantly inhibited AKT/GSK3ß/mTORC1 signaling. Besides the classic AT1 inhibition, VAL treatment significantly inhibited MAPK (ERK1/2) signaling. Furthermore, VAL and PER treatment could markedly prevent neonatal rat cardiomyocyte hypertrophy and the activation of neonatal rat cardiac fibroblast. Combination of VAL and PER also presented superior beneficial effects than single treatment of VAL or PER in vitro experiments respectively. This study presented that the combination of valsartan and PER may be a potential treatment for HF prevention.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32367240

RESUMO

Effects of turbulent energy dissipation rate (increased from 1.28 × 10-6 to 1.67 × 10-5 m2 s-3) on Scenedesmus obliquus biomass and lipid accumulation at different aeration rates (0.3, 0.6, 0.9, 1.2, and 1.5 L min-1) were investigated. The turbulent energy dissipation rate was calculated by CFD model simulation. When the turbulent energy dissipation rate increased to 7.30 × 10-6 m2 s-3, the biomass and lipid productivity increased gradually, and finally reached their maximum values of 1.11 × 107 cells mL-1 and 16.0 mg L-1 day-1, respectively. When it exceeded 7.30 × 10-6 m2 s-3, the biomass and lipid productivity showed a decreasing trend. Therefore, the most favorable turbulent energy dissipation rate for S. obliquus growth and lipid accumulation was 7.30 × 10-6 m2 s-3.

3.
Nanoscale ; 12(14): 7864-7869, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32227024

RESUMO

Single crystals of a small bimetallic Ag3Cu2 nanocluster protected by six ligands of 2,4-dimethylbenzene thiol are synthesized by a one-pot procedure of wet chemistry. This Ag3Cu2 nanocluster bears a trigonal bipyramid metallic core with two copper atoms located on both sides of a triangular Ag3. Interestingly, the six Cu-Ag side edges of the trigonal bipyramid are fully protected by the six ligands giving rise to reinforced stability and high chemical purity. More interestingly, this Ag3Cu2 cluster shows strong dual fluorescence emissions in both ultraviolet visible (UV-vis) and near infrared (NIR) regions. Theoretical calculations reproduce the absorption and fluorescence spectra where the NIR emission at 824 nm is assigned to the S1 → S0 transition, while the simultaneous emission in the visible band is due to the radiation of highly excited states and is against Kasha's rule.

4.
Int J Mol Med ; 45(5): 1425-1435, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32323841

RESUMO

Corosolic acid (CRA) is a pentacyclic triterpenoid isolated from Lagerstroemia speciosa. The aim of the present study was to determine whether CRA reduces cardiac remodelling following myocardial infarction (MI) and to elucidate the underlying mechanisms. C57BL/6J mice were randomly divided into control (PBS­treated) or CRA­treated groups. After 14 days of pre­treatment, the mice were subjected to either sham surgery or permanent ligation of the left anterior descending artery. Following surgery, all animals were treated with PBS or CRA (10 or 20 mg/kg/day) for 4 weeks. After 4 weeks, echocardiographic, haemodynamic, gravimetric, histological and biochemical analyses were conducted. The results revealed that, upon MI, mice with CRA treatment exhibited decreased mortality rates, improved ventricular function and attenuated cardiac fibrosis compared with those in control mice. Furthermore, CRA treatment resulted in reduced oxidative stress, inflammation and apoptosis, as well as inhibited the transforming growth factor ß1/Smad signalling pathway activation in cardiac tissue. In vitro studies further indicated that inhibition of AMP­activated protein kinase α (AMPKα) reversed the protective effect of CRA. In conclusion, the study revealed that CRA attenuated MI­induced cardiac fibrosis and dysfunction through modulation of inflammation and oxidative stress associated with AMPKα.

5.
Cell Death Dis ; 11(3): 160, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123163

RESUMO

High-mobility group AT-hook1 (HMGA1, formerly HMG-I/Y), an architectural transcription factor, participates in a number of biological processes. However, its effect on cardiac remodeling (refer to cardiac inflammation, apoptosis and dysfunction) in diabetic cardiomyopathy remains largely indistinct. In this study, we found that HMGA1 was upregulated in diabetic mouse hearts and high-glucose-stimulated cardiomyocytes. Overexpression of HMGA1 accelerated high-glucose-induced cardiomyocyte inflammation and apoptosis, while HMGA1 knockdown relieved inflammation and apoptosis in cardiomyocytes in response to high glucose. Overexpression of HMGA1 in mice heart by adeno-associated virus 9 (AAV9) delivery system deteriorated the inflammatory response, increased apoptosis and accelerated cardiac dysfunction in streptozotocin-induced diabetic mouse model. Knockdown of HMGA1 by AAV9-shHMGA1 in vivo ameliorated cardiac remodeling in diabetic mice. Mechanistically, we found that HMGA1 inhibited the formation rather than the degradation of autophagy by regulating P27/CDK2/mTOR signaling. CDK2 knockdown or P27 overexpression blurred HMGA1 overexpression-induced deteriorating effects in vitro. P27 overexpression in mice heart counteracted HMGA1 overexpression-induced increased cardiac remodeling in diabetic mice. The luciferase reporter experiment confirmed that the regulatory effect of HMGA1 on P27 was mediated by miR-222. In addition, a miR-222 antagomir counteracted HMGA1 overexpression-induced deteriorating effects in vitro. Taken together, our data indicate that HMGA1 aggravates diabetic cardiomyopathy by directly regulating miR-222 promoter activity, which inhibits P27/mTOR-induced autophagy.

6.
Bioresour Technol ; 302: 122903, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32018084

RESUMO

Screening for highly efficient microalgae is an important technique for improving treatment efficiency. In this study, eight species of microalgae (five Scenedesmus and three Desmodesmus) were isolated from water and soil in the Hexi Corridor region, China, and identified by 18S rRNA gene sequence analysis. Scenedesmus sp. HXY2 grew well under high total organic carbon and ammonia conditions and had the highest nutrient removal efficiency (>95%). On day 12, the biomass of Scenedesmus sp. HXY2 was 7.2 × 106 cells mL-1. The lipid content and productivity of this species were 15.56% and 5.67 mg L-1 day-1, respectively. The proportion of unsaturated fatty acids (60.07%) indicated that the lipids of Scenedesmus sp. HXY2 were suitable for biodiesel production. Scenedesmus sp. HXY2 showed great potential for growth in wastewater with high ammonia and organic contents to simultaneously purify wastewater and produce lipids.


Assuntos
Microalgas , Scenedesmus , Biocombustíveis , Biomassa , China , Lipídeos , Águas Residuárias
7.
J Environ Manage ; 260: 110152, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32090842

RESUMO

Vertical flow constructed wetlands are facing the problem of low removal efficiency when treating high-load wastewater. This study explored the effect of oxygen supplement (1.2, 1.0, 0.8 L min-1 for 6 h; 1.0 L min-1 for 4 h and 2 h) on enhancing nitrogen removal in vertical flow constructed wetlands modified by adding biochar for treating secondary livestock effluent. The results indicated that biochar addition could enhance contaminant removal due to its adsorption of contaminants under the condition of no aeration. Additionally, the aeration addition of 1.0 L min-1 for 2 h per day in biochar-based constructed wetlands achieved the high efficiencies for chemical oxygen demand (95%) and total nitrogen (73%) removal. However, total nitrogen removal efficiency in biochar-based constructed wetlands declined under excessive dissolved oxygen conditions which might restrain the denitrification process. Average nitrous oxide emission fluxes in biochar-based constructed wetlands (575-1877 µg m-2 h-1) were lower than those in non-biochar constructed wetlands (745-2298 µg m-2 h-1). In addition, the variation of N2O emission under different aeration conditions was similar with the maximum value at the aeration condition of 1.2 L min-1 for 6 h d-1. These results could be useful for improving the sustainable design and operation of constructed wetlands for high-load wastewater treatments.


Assuntos
Nitrogênio , Áreas Alagadas , Animais , Análise da Demanda Biológica de Oxigênio , Carvão Vegetal , Desnitrificação , Gado , Oxigênio , Eliminação de Resíduos Líquidos , Águas Residuárias
8.
Gen Physiol Biophys ; 39(1): 59-67, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32039825

RESUMO

MT1JP is a LncRNA that is reportedly involved in gastric cancer development, but a biological role and mechanism for MT1JP in breast cancer is unknown. Quantitative RT-PCR was performed to detect the level of MT1JP and miR-92a-3p, and Western blotting assays ware performed to measure the expression of CDK2, cyclinE1, P21, CD151, CD147, MMP2 and MMP9 in breast cells. Subsequently, cell viability was analyzed with CCK-8 assay. Cell migration and invasion were analyzed with Transwell and Scratch Test, respectively. The results demonstrated that MT1JP was significantly down-regulated in breast cells. Additionally, we found that overexpression of MT1JP in breast cancer cells significantly inhibited cell proliferation, migration and invasion, and regulate the expression of CDK2, cyclinE1 and P21. We then investigated a possible mechanism for these results, MT1JP significantly inhibited CD151, CD147, MMP2 and MMP9 protein expression in breast cancer cells. Moreover, we found that MT1JP binds to and negatively regulates miR-92-3p, which is known to be an oncogene in some human cancers. Our data indicate that MT1JP functions as an anti-tumor LncRNA and downregulates miR-92-3p, CD151 and CD147, and may serve as a novel diagnostic and therapeutic marker in breast cancer.


Assuntos
Neoplasias da Mama , MicroRNAs/genética , RNA Longo não Codificante/genética , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos
9.
J Phys Chem A ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32091897

RESUMO

Utilizing a magnetron-sputtering (MagS) source in tandem with a multiple-ion laminar flow tube (MIFT) reactor and a customized triple quadrupole mass spectrometer (TQMS), we have prepared clean Pbn+ (n = 1-13) clusters and measured their reactivity with iodomethane under high carrier gas pressures. Strong size dependences are found for the reactivity of these cationic Pbn+ clusters with CH3I. For the Pbn+ with n ≤ 4, iodinated clusters PbnI+ were found to be the dominant products, in strong contrast to n > 4 where no such products were seen. Quantum chemical studies show that with an increasing number of Pb atoms, the Pb-Pb interatomic interactions become stronger compared with the Pb-I bonding in PbnI+ clusters. Furthermore, the reactions of Pb1-4+ with CH3I have fairly small transition state energy barriers, in contrast to those for Pbn>4+ clusters which have magnitudes that will prevent reactions under the ambient conditions.

10.
Phys Chem Chem Phys ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32107522

RESUMO

Correction for 'A hexagonal Ni6 cluster protected by 2-phenylethanethiol for catalytic conversion of toluene to benzaldehyde' by Anthony M. S. Pembere et al., Phys. Chem. Chem. Phys., 2019, 21, 17933-17938.

11.
J Clin Lab Anal ; : e23172, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907990

RESUMO

BACKGROUND: In previous research, we found diabetes rather than obesity was an independent risk factor of breast cancer. However, why diabetes could lead to increased risk of breast cancer patients remains elusive. Long non-coding RNAE330013P06 has been shown to be upregulated in diabetes, and long non-coding RNAs generally promote progression of cancer. METHODS: About 200 specimens of breast patients were obtained in previous clinical trial; 34 samples diagnosed as type 2 diabetes in breast cancer patient were enrolled in this research. Blood samples from 36 patients diagnosed as breast cancer without diabetes; 35 diabetic patients and 35 healthy peoples were obtained as control. All blood samples were measured by quantitative real-time PCR (qRT-PCR). Invasion and migration were tested by Transwell assay. Cell proliferation assay was tested by CCK-8. Protein analysis was determined by Western blot. RESULTS: Compared with breast cancer patients without diabetes, diabetic patients without breast cancer and healthy peoples, LncRNAE330013P06 was upregulated in breast cancer patient with diabetes. Furthermore, of 34 breast patients, high LncRNAE330013P06 expression was significantly associated with family history, tumor-node-metastasis stage and lymph node metastasis. E33 promoted cancer cell growth in vitro via downregulation of P53. CONCLUSION: Upregulation of LncRNAE330013P06 driven by type 2 diabetes is one of the factors which promoted progression of breast cancer.

12.
Cell Death Differ ; 27(2): 540-555, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31209361

RESUMO

Oxidative stress and cardiomyocyte apoptosis play critical roles in doxorubicin (DOX)-induced cardiotoxicity. Previous studies indicated that fibronectin type III domain-containing 5 (FNDC5) and its cleaved form, irisin, could preserve mitochondrial function and attenuate oxidative damage as well as cell apoptosis, however, its role in DOX-induced cardiotoxicity remains unknown. Our present study aimed to investigate the role and underlying mechanism of FNDC5 on oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity. Cardiomyocyte-specific FNDC5 overexpression was achieved using an adeno-associated virus system, and then the mice were exposed to a single intraperitoneal injection of DOX (15 mg/kg) to generate DOX-induced cardiotoxicity. Herein, we found that FNDC5 expression was downregulated in DOX-treated murine hearts and cardiomyocytes. Fndc5 deficiency resulted in increased oxidative damage and apoptosis in H9C2 cells under basal conditions, imitating the phenotype of DOX-induced cardiomyopathy in vitro, conversely, FNDC5 overexpression or irisin treatment alleviated DOX-induced oxidative stress and cardiomyocyte apoptosis in vivo and in vitro. Mechanistically, we identified that FNDC5/Irisin activated AKT/mTOR signaling and decreased DOX-induced cardiomyocyte apoptosis, and moreover, we provided direct evidence that the anti-oxidant effect of FNDC5/Irisin was mediated by the AKT/GSK3ß/FYN/Nrf2 axis in an mTOR-independent manner. And we also demonstrated that heat shock protein 20 was responsible for the activation of AKT caused by FNDC5/Irisin. In line with the data in acute model, we also found that FNDC5/Irisin exerted beneficial effects in chronic model of DOX-induced cardiotoxicity (5 mg/kg, i.p., once a week for three times, the total cumulative dose is 15 mg/kg) in mice. Based on these findings, we supposed that FNDC5/Irisin was a potential therapeutic agent against DOX-induced cardiotoxicity.

13.
Water Res ; 169: 115285, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31722275

RESUMO

Groundwater, as the most important drinking water source in arid regions of China, has been polluted seriously by accumulated nitrate and heavy metals. An economic alternative with capacity of simultaneous mitigation of nitrate and heavy metals is urgently needed. This study explored the incorporation of iron scraps and biochar into constructed wetlands (CWs) for enhancing purification performance and investigated interactions of effective nitrate reduction and heavy metals mitigation. The results showed that nitrate reduction performance could reach 87% in iron and carbon-based (Fe-C) CWs through Fe-C micro-electrolysis process, with lower nitrous oxide (N2O) emission (4.6-11.75 µg m-2 h-1) due to the complete denitrification process. Moreover, efficient heavy metals mitigation of 75-97% total chromium (Cr) and total lead (Pb) was obtained from Fe-C systems. However, the occurrence of heavy metals (Cr and Pb) in the influent posed an adverse impact on nitrate removal with the reduction rate of 19-43%. Biochemical characteristics of wetland plants indicated that the plants also suffered from the stress which induced from heavy metals. Overall, although the addition of iron and biochar in CWs enhanced nitrate and heavy metals removal in low carbon groundwater, further investigation is still needed to reveal the complex relationships between the removal of nitrate and heavy metals in CWs.


Assuntos
Água Subterrânea , Metais Pesados , Poluentes Químicos da Água , Carbono , China , Ferro , Eliminação de Resíduos Líquidos , Áreas Alagadas
14.
Ecotoxicol Environ Saf ; 187: 109809, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31654861

RESUMO

A theoretical non-linear combined toxicity assessment method is proposed and evaluated using Microcystis aeruginosa as the test organism. The combined toxicity of binary heavy metals was evaluated by comparing the actual inhibitory rates shown from the experiments with the theoretically calculated inhibitory rates. It was identified that the binary mixtures of Cu2++ Cd2+, Cu2++ Cr3+ and Zn2++ Cr3+ had the synergistic effects when the combined concentrations were low, but exhibited the antagonistic effects with the higher combined concentrations. Furthermore, the toxic effect of Pb2+ was not influenced by the addition of Cu2+ when combined concentration was low, but it was enhanced by Cu2+ at the high combined concentration. The binary mixtures of Zn2++ Cd2+, Pb2++ Cr3+, Pb2++ Cd2+, Pb2++ Zn2+, and Cr3++ Cd2+ always presented antagonistic effects, while the synergistic toxicity effect on M. aeruginosa was observed for the binary mixtures of Cu2++ Zn2+ regardless of combined concentration. The proposed assessment method was also validated by the antioxidant enzyme activity, which showed synergistic or antagonistic effects under different binary mixtures of heavy metals.


Assuntos
Metais Pesados/toxicidade , Microcystis/efeitos dos fármacos , Modelos Teóricos , Antioxidantes/metabolismo , Sinergismo Farmacológico , Malondialdeído/metabolismo , Metais Pesados/química , Microcystis/enzimologia , Dinâmica não Linear , Espécies Reativas de Oxigênio/metabolismo
15.
Oxid Med Cell Longev ; 2019: 6304058, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885808

RESUMO

Myricetin (Myr) is a common plant-derived polyphenol and is well recognized for its multiple activities including antioxidant, anti-inflammation, anticancer, and antidiabetes. Our previous studies indicated that Myr protected mouse heart from lipopolysaccharide and streptozocin-induced injuries. However, it remained to be unclear whether Myr could prevent mouse heart from pressure overload-induced pathological hypertrophy. Wild type (WT) and cardiac Nrf2 knockdown (Nrf2-KD) mice were subjected to aortic banding (AB) surgery and then administered with Myr (200 mg/kg/d) for 6 weeks. Myr significantly alleviated AB-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction in both WT and Nrf2-KD mice. Myr also inhibited phenylephrine- (PE-) induced neonatal rat cardiomyocyte (NRCM) hypertrophy and hypertrophic markers' expression in vitro. Mechanically, Myr markedly increased Nrf2 activity, decreased NF-κB activity, and inhibited TAK1/p38/JNK1/2 MAPK signaling in WT mouse hearts. We further demonstrated that Myr could inhibit TAK1/p38/JNK1/2 signaling via inhibiting Traf6 ubiquitination and its interaction with TAK1 after Nrf2 knockdown in NRCM. These results strongly suggested that Myr could attenuate pressure overload-induced pathological hypertrophy in vivo and PE-induced NRCM hypertrophy via enhancing Nrf2 activity and inhibiting TAK1/P38/JNK1/2 phosphorylation by regulating Traf6 ubiquitination. Thus, Myr might be a potential strategy for therapy or adjuvant therapy for malignant cardiac hypertrophy.

16.
J Phys Chem A ; 123(50): 10739-10745, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31765562

RESUMO

Hydrogenation of organic chemicals is one of the most frequent things that people take for granted in mass spectroscopy; however, it could provide important information on spontaneous or stimulated hydrogen transfer in initiating chemical reactions and in determining the product selectivity and conversion efficiency. Here, we present a study of hydrogenation of acetone via vacuum ultraviolet laser ionization mass spectrometry (VUV-LIMS) and density functional theory (DFT) calculations. It is interestingly found that acetone dimer readily captures a hydrogen to form (C3H6O)2H+ in the presence of alcohols, shedding light on the intracluster hydrogen atom transfer via a trimolecular mechanism. This is well consistent with the DFT calculation results of energetics and reaction kinetics. It is worth noting that, although the hydrogen bond interaction of O-H···O is stronger than that of C-H···O, the hydrogen atom transfer (HAT) tends to proceed from the methyl group of the alcohols to acetone. We fully demonstrate the intracluster HAT reactivity of such a simple system and provide new insights into hydrogen bond interactions and molecular cluster chemistry.

17.
Sci Total Environ ; 692: 613-621, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31539969

RESUMO

Dissolved organic matter (DOM) is a natural chemical component of all soils and influences soil organic pollutant migration, nutrient cycling, and global climate change. Previous field studies have focused on a single ecosystem, such as cropland, grassland, or forestland. However, the potential effect of different land-use types on the vertical distribution of soil DOM quantity and quality remains unclear. This study investigated the vertical characteristics of DOM in 5-m soil profiles under different land-use types (cropland, grassland, and forestland) on the Loess Plateau. The data from ultraviolet-visible spectral and parallel factor analysis of fluorescence excitation-emission matrix spectrophotometry were combined. These results indicated that the mean content of dissolved organic carbon (DOC) in the 30-yr forestland (203.33 mg kg-1 soil) was the highest, and the lowest was observed in the cropland (83.70 mg kg-1 soil). Meanwhile, the mean DOC content of the forestland increased through time, particularly after 20 years. In other words, afforestation activities only significantly affected soil DOM after a long time (over 20 years). The DOC content of the cropland initially increased and then decreased with soil depth in the 1-m soil profiles, which may be related to agricultural activities. Three fluorescence components, including two humic acid-like substances (C1 and C3) and a tryptophan-like substance (C2), were identified from all samples. The humic acid-like components significantly decreased by 51% with soil depth, while the tryptophan-like component increased by 49%, particularly in the cropland. The variation in ultraviolet-visible spectral and optical indexes also indicated that soil DOM was dominated by both microbial and terrestrial sources. These findings help to understand the dynamics of DOC in deep soil profiles and the biogeochemical effects of DOM in the natural environment.

18.
Phys Chem Chem Phys ; 21(32): 17933-17938, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31380877

RESUMO

We have synthesized single crystals of a 2-phenylethanethiol-protected Ni6 nanocluster, namely Ni6(C8H9S)12, which shows a hexagonal metallic core structure and reasonable stability. Interestingly this cluster is found to be an excellent candidate for the catalytic oxidation of toluene to benzaldehyde, with 100% conversion and 91% selectivity, showing application potential as an aromatic aldehyde in industry. Using DFT calculations, we rationalize the catalytic reaction mechanism for the conversion of toluene to benzaldehyde, and demonstrate that the presence of H2O2 initiates the Ni6 cluster via a highly exothermic step to form a Ni6O* intermediate which then results in active sites for the oxidation of toluene. What is interesting is that the likely steric geometry matching of the six-ring Ni6 core, a dozen phenylethanethiol ligands and the aromatic reactant toluene could attain a synergistic effect to facilitate the production of benzaldehyde free of catalyst support.

19.
Int J Mol Med ; 44(4): 1447-1461, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364721

RESUMO

Cardiac remodeling predisposes to heart failure if the burden is unresolved, and heart failure is an important cause of mortality in humans. The aim of the present study was to identify the key genes involved in cardiac pathological remodeling induced by pressure overload. Gene expression profiles of the GSE5500, GSE18224, GSE36074 and GSE56348 datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs), defined as |log2FC|>1 (FC, fold change) and an adjusted P­value of <0.05, were screened using the R software with the limma package. Gene ontology enrichment analysis was performed and a protein­protein interaction (PPI) network of the DEGs was constructed. A cardiac remodeling model induced by transverse aortic constriction (TAC) was established. Furthermore, consistent DEGs were further validated using reverse transcription­quantitative polymerase chain reaction (RT­PCR) analysis, western blotting and immunohistochemistry in the ventricular tissue samples after TAC or sham operation. A total of 24 common DEGs were identified (23 significantly upregulated and 1 downregulated), of which 9 genes had been previously confirmed to be directly involved in cardiac remodeling. Hence, the level of expression of the other 15 genes was detected in subsequent studies via RT­PCR. Based on the results of the PPI network analysis and RT­PCR, we further detected the protein levels of Itgbl1 and Asporin, which were consistent with the results of bioinformatics analysis and RT­PCR. The expression of Itgbl1, Aspn, Fstl1, Mfap5, Col8a1, Ltbp2, Mfap4, Pamr1, Cnksr1, Aqp8, Meox1, Gdf15 and Srpx was found to be upregulated in a mouse model of cardiac remodeling, while that of Retnla was downregulated. Therefore, the present study identified the key genes implicated in cardiac remodeling, aiming to provide new insight into the underlying mechanism.


Assuntos
Aorta/fisiopatologia , Perfilação da Expressão Gênica , Transcriptoma , Vasoconstrição , Remodelação Ventricular/genética , Animais , Biomarcadores , Biologia Computacional/métodos , Bases de Dados Genéticas , Modelos Animais de Doenças , Feminino , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Masculino , Camundongos , Miócitos Cardíacos/metabolismo , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/genética , Ratos , Reprodutibilidade dos Testes
20.
Acta Pharm Sin B ; 9(4): 690-701, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31384530

RESUMO

Oxidative stress and cardiomyocyte apoptosis are involved in the pathogenesis of doxorubicin (DOX)-induced cardiotoxicity. Matrine is well-known for its powerful anti-oxidant and anti-apoptotic capacities. Our present study aimed to investigate the effect of matrine on DOX-induced cardiotoxicity and try to unearth the underlying mechanisms. Mice were exposed with DOX to generate DOX-induced cardiotoxicity or normal saline as control. H9C2 cells were used to verify the effect of matrine in vitro. DOX injection triggered increased generation of reactive oxygen species (ROS) and excessive cardiomyocyte apoptosis, which were significantly mitigated by matrine. Mechanistically, we found that matrine ameliorated DOX-induced uncoupling protein 2 (UCP2) downregulation, and UCP2 inhibition by genipin could blunt the protective effect of matrine on DOX-induced oxidative stress and cardiomyocyte apoptosis. Besides, 5'-AMP-activated protein kinase α2 (Ampkα2) deficiency inhibited matrine-mediated UCP2 preservation and abolished the beneficial effect of matrine in mice. Besides, we observed that matrine incubation alleviated DOX-induced H9C2 cells apoptosis and oxidative stress level via activating AMPKα/UCP2, which were blunted by either AMPKα or UCP2 inhibition with genetic or pharmacological methods. Matrine attenuated oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity via maintaining AMPKα/UCP2 pathway, and it might be a promising therapeutic agent for the treatment of DOX-induced cardiotoxicity.

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