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1.
Plant Physiol ; 193(3): 2164-2179, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37610417

RESUMO

The lipid transport protein (LTP) product of the AsE246 gene of Chinese milk vetch (Astragalus sinicus) contributes to the transport of plant-synthesized lipids to the symbiosome membranes (SMs) that are required for nodule organogenesis in this legume. However, the mechanisms used by nodule-specific LTPs remain unknown. In this study, a functional protein in the DnaJ-like family, designated AsDJL1, was identified and shown to interact with AsE246. Immunofluorescence showed that AsDJL1 was expressed in infection threads (ITs) and in nodule cells and that it co-localized with rhizobium, and an immunoelectron microscopy assay localized the protein to SMs. Via co-transformation into Nicotiana benthamiana cells, AsDJL1 and AsE246 displayed subcellular co-localization in the cells of this heterologous host. Co-immunoprecipitation assays confirmed that AsDJL1 interacted with AsE246 in nodules. The essential interacting region of AsDJL1 was determined to be the zinc finger domain at its C-terminus. Chinese milk vetch plants transfected with AsDJL1-RNAi had significantly decreased numbers of ITs, nodule primordia and nodules as well as reduced (by 83%) nodule nitrogenase activity compared with the controls. By contrast, AsDJL1 overexpression led to increased nodule fresh weight and nitrogenase activity. RNAi-AsDJL1 also significantly affected the abundance of lipids, especially digalactosyldiacylglycerol, in early-infected roots and transgenic nodules. Taken together, the results of this study provide insights into the symbiotic functions of AsDJL1, which may participate in lipid transport to SMs and play an essential role in rhizobial infection and nodule organogenesis.


Assuntos
Astrágalo , Fabaceae , Rhizobium , Fixação de Nitrogênio/genética , Nódulos Radiculares de Plantas/genética , Nódulos Radiculares de Plantas/metabolismo , Proteínas de Transporte/metabolismo , Astrágalo/metabolismo , Nitrogenase/metabolismo , Lipídeos , Simbiose/genética , Nodulação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
2.
Clin Exp Pharmacol Physiol ; 51(8): e13872, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38886134

RESUMO

Atherosclerosis, a lipid-driven chronic inflammatory disorder, is a significant global health concern associated with high rates of morbidity and mortality, imposing a substantial societal burden. The purpose of this study is to investigate the possible molecular mechanisms of atherosclerosis and identify potential therapeutic targets. We conducted an integrated bioinformatics analysis using data from peripheral blood mononuclear cell and TISSUE databases obtained from the Gene Expression Omnibus, to identify key genes associated with the progression of atherosclerosis. Here, IRF8 was found to be a key gene in atherosclerosis patients. Silencing IRF8 with small interfering RNA reduced inflammation in endothelial cells. This suggests IRF8 is a crucial biomarker for immune infiltration in atherosclerosis advance.


Assuntos
Aterosclerose , Biomarcadores , Biologia Computacional , Fatores Reguladores de Interferon , Humanos , Aterosclerose/genética , Aterosclerose/imunologia , Biologia Computacional/métodos , Fatores Reguladores de Interferon/genética , Biomarcadores/metabolismo , Inflamação/genética , Inflamação/imunologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-38937951

RESUMO

A 50-day feeding trial was conducted to evaluate the effects of mulberry leaf powder water extract (MLE) on the growth performance, immunity, antioxidant, meat quality and intestinal microbiota of yellow feather broilers. A total of 720 birds (initial body weight 40.07 ± 0.05 g) were randomly distributed into four groups with six replicates per group and 30 birds per replicate. Four diets were formulated with 0% (CON), 200 mg/kg MLE (MLE200), 400 mg/kg MLE (MLE400) and 600 mg/kg MLE (MLE600) supplementation. Results showed that the addition of 200-600 mg/kg MLE to the diet significantly increased the body weight (BW) and average daily weight gain (ADG), but feed to gain ratio (F/G) were linearly decreased (p = 0.045) as dietary MLE increased. Birds fed MLE400 had higher (p < 0.05) total antioxidant capacity (T-AOC), interleukin-10 (Il-10), secretory immunoglobulin A (SIgA) and complement 3 (C3) contents than those fed CON, whereas MLE400 had lower malondialdehyde (MDA) content than CON (p < 0.05). Analysis of 16 S rDNA indicated that supplementation with 200 mg/kg MLE increased the Shannon indices in the caecum (p < 0.05). Supplementation with MLE decreased the abundance of the phylum Proteobacteria and genus Helicobacter, and increased the abundance of the phylum Bacteroidetes in the caecum in broiler chickens (p < 0.05). The drip loss rate in the MLE600 was significantly diminished (p < 0.05), whereas the shear force was significantly elevated (p < 0.05). In summary, dietary supplementation with MLE can effectively improve growth performance, intestinal immunity, serum antioxidant capacity, meat quality and intestinal microbiota of yellow feather broilers. The most appropriate MLE supplementation level was 400 mg/kg. This study provides a practical strategy for the dietary application of MLE in yellow feather broilers.

4.
J Am Chem Soc ; 145(49): 26817-26823, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38019281

RESUMO

Generative artificial intelligence has depicted a beautiful blueprint for on-demand design in chemical research. However, the few successful chemical generations have only been able to implement a few special property values because most chemical descriptors are mathematically discrete or discontinuously adjustable. Herein, we use spectroscopic descriptors with machine learning to establish a quantitative spectral structure-property relationship for adsorbed molecules on metal monatomic catalysts. Besides catalytic properties such as adsorption energy and charge transfer, the complete spatial relative coordinates of the adsorbed molecule were successfully inverted. The spectroscopic descriptors and prediction models are generalized, allowing them to be transferred to several different systems. Due to the continuous tunability of the spectroscopic descriptors, the design of catalytic structures with continuous adsorption states generated by AI in the catalytic process has been achieved. This work paves the way for using spectroscopy to enable real-time monitoring of the catalytic process and continuous customization of catalytic performance, which will lead to profound changes in catalytic research.

5.
BMC Microbiol ; 23(1): 57, 2023 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-36869296

RESUMO

BACKGROUND: Heavy metal pollution has become a major source of environmental pollution because of increasing industrialization. Microbial remediation is a promising approach to remediate lead-contaminated environments owing to its cost-effective, environment-friendly, ecologically sustainable, and highly efficient properties. In this study, the growth-promoting functions and lead-adsorption ability of Bacillus cereus SEM-15 were examined, and the functional mechanism of the strain was preliminarily identified using scanning electron microscopy, energy spectrum, infrared spectrum, and genome analyses, providing theoretical support for utilization of B. cereus SEM-15 in heavy metals remediation. RESULTS: B. cereus SEM-15 showed strong ability to dissolve inorganic phosphorus and secrete indole-3-acetic acid. The lead adsorption efficiency of the strain at lead ion concentration of 150 mg/L was more than 93%. Single factor analysis revealed the optimal conditions for heavy metal adsorption by B. cereus SEM-15 (adsorption time, initial lead ion concentration, pH, and inoculum amount were 10 min, 50-150 mg/L, 6-7, and 5 g/L, respectively) in nutrient-free environment, with the lead adsorption rate reaching 96.58%. Scanning electron microscopy of B. cereus SEM-15 cells before and after lead adsorption showed adherence of a large number of granular precipitates to the cell surface after lead adsorption. X-Ray photoelectron spectroscopy and Fourier transform infrared spectroscopy results indicated the characteristic peaks of Pb-O, Pb-O-R (R = functional group), and Pb-S bonds after lead adsorption, and a shift in the characteristic peaks of bonds and groups related to C, N, and O. Genome annotation results showed the presence of genes related to heavy metals tolerance and plant growth promotion in B. cereus SEM-15, providing a molecular basis for the strain's heavy metals tolerance and plant growth promotion functions. CONCLUSIONS: This study analyzed the lead adsorption characteristics of B. cereus SEM-15 and the associated influencing factors, and discussed the adsorption mechanism and related functional genes, providing a basis for clarifying the underlying molecular mechanism and offering a reference for further research on plant-microorganisms combined remediation of heavy metals polluted environments.


Assuntos
Bacillus cereus , Chumbo , Adsorção , Solubilidade , Fósforo
6.
Mol Plant Microbe Interact ; 35(10): 893-905, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35762679

RESUMO

Legumes in the inverted repeat-lacking clade (IRLC) each produce a unique set of nodule-specific cysteine-rich (NCR) peptides, which act in concert to determine the terminal differentiation of nitrogen-fixing bacteroid. IRLC legumes differ greatly in their numbers of NCR and sequence diversity. This raises the significant question how bacteroid differentiation is collectively controlled by the specific NCR repertoire of an IRLC legume. Astragalus sinicus is an IRLC legume that forms indeterminate nodules with its microsymbiont Mesorhizobium huakuii 7653R. Here, we performed transcriptome analysis of root and nodule samples at 3, 7, 14, 28 days postinoculation with M. huakuii 7653R and its isogenic ∆bacA mutant. BacA is a broad-specificity peptide transporter required for the host-derived NCRs to target rhizobial cells. A total of 167 NCRs were identified in the RNA transcripts. Comparative sequence and electrochemical analysis revealed that A. sinicus NCRs (AsNCRs) are dominated by a unique cationic group (termed subgroup C), whose mature portion is relatively long (>60 amino acids) and phylogenetically distinct and possessing six highly conserved cysteine residues. Subsequent functional characterization showed that a 7653R variant harboring AsNCR083 (a representative of subgroup C AsNCR) displayed significant growth inhibition in laboratory media and formed ineffective white nodules on A. sinicus with irregular symbiosomes. Finally, bacterial two-hybrid analysis led to the identification of GroEL1 and GroEL3 as the molecular targets of AsNCR067 and AsNCR076. Together, our data contribute to a systematic understanding of the NCR repertoire associated with the A. sinicus and M. huakuii symbiosis. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Assuntos
Cisteína , Fabaceae , Cisteína/química , Cisteína/genética , Cisteína/metabolismo , Fabaceae/microbiologia , Nitrogênio/metabolismo , Fixação de Nitrogênio/genética , Peptídeos/metabolismo , RNA/metabolismo , Nódulos Radiculares de Plantas/microbiologia , Simbiose/genética , Transcriptoma/genética
7.
Mol Plant Microbe Interact ; 34(5): 547-559, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33596109

RESUMO

Rhizobia are rod-shaped bacteria that form nitrogen-fixing root nodules on leguminous plants; however, they don't carry MreB, a key determinant of rod-like cell shape. Here, we introduced an actin-like mreB homolog from a pseudomonad into Mesorhizobium huakuii 7653R (a microsymbiont of Astragalus sinicus L.) and examined the molecular, cellular, and symbiotic phenotypes of the resultant mutant. Exogenous mreB caused an enlarged cell size and slower growth in laboratory medium. However, the mutant formed small, ineffective nodules on A. sinicus (Nod+ Fix-), and rhizobial cells in the infection zone were unable to differentiate into bacteroids. RNA sequencing analysis also revealed minor effects of mreB on global gene expression in free-living cells but larger effects for cells grown in planta. Differentially expressed nodule-specific genes include cell cycle regulators such as the tubulin-like ftsZ1 and ftsZ2. Unlike the ubiquitous FtsZ1, an FtsZ2 homolog was commonly found in Rhizobium, Sinorhizobium, and Mesorhizobium spp. but not in closely related nonsymbiotic species. Bacterial two-hybrid analysis revealed that MreB interacts with FtsZ1 and FtsZ2, which are targeted by the host-derived nodule-specific cysteine-rich peptides. Significantly, MreB mutation D283A disrupted the protein-protein interactions and restored the aforementioned phenotypic defects caused by MreB in M. huakuii. Together, our data indicate that MreB is detrimental for modern rhizobia and its interaction with FtsZ1 and FtsZ2 causes the symbiotic process to cease at the late stage of bacteroid differentiation. These findings led to a hypothesis that loss of mreB in the common ancestor of members of Rhizobiales and subsequent acquisition of ftsZ2 are critical evolutionary steps leading to legume-rhizobial symbiosis.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Assuntos
Fabaceae , Rhizobium , Proteínas do Citoesqueleto , Mesorhizobium , Fixação de Nitrogênio , Nódulos Radiculares de Plantas , Simbiose
8.
Plant Physiol ; 180(1): 509-528, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30765481

RESUMO

Plant nonspecific lipid transfer proteins (nsLTPs) are involved in a number of biological processes including root nodule symbiosis. However, the role of nsLTPs in legume-rhizobium symbiosis remains poorly understood, and no rhizobia proteins that interact with nsLTPs have been reported to date. In this study, we used a bacteria two-hybrid system and identified the high temperature protein G (HtpG) from Mesorhizobium huakuii that interacts with the nsLTP AsE246. The interaction between HtpG and AsE246 was confirmed by far-Western blotting and bimolecular fluorescence complementation. Our results indicated that the heat shock protein 90 (HSP90) domain of HtpG mediates the HtpG-AsE246 interaction. Immunofluorescence assay showed that HtpG was colocalized with AsE246 in infected nodule cells and symbiosome membranes. Expression of the htpG gene was relatively higher in young nodules and was highly expressed in the infection zones. Further investigation showed that htpG expression affects lipid abundance and profiles in root nodules and plays an essential role in nodule development and nitrogen fixation. Our findings provide further insights into the functional mechanisms behind the transport of symbiosome lipids via nsLTPs in root nodules.


Assuntos
Astrágalo/microbiologia , Proteínas de Bactérias/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Mesorhizobium/fisiologia , Fixação de Nitrogênio/fisiologia , Proteínas de Plantas/metabolismo , Astrágalo/metabolismo , Proteínas de Bactérias/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Regulação Bacteriana da Expressão Gênica , Proteínas de Choque Térmico HSP90/genética , Mutação , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Domínios Proteicos , Mapas de Interação de Proteínas , Nódulos Radiculares de Plantas/metabolismo , Nódulos Radiculares de Plantas/microbiologia , Simbiose , Nicotiana/genética , Nicotiana/metabolismo , Nicotiana/microbiologia , Técnicas do Sistema de Duplo-Híbrido
9.
Clin Exp Pharmacol Physiol ; 45(2): 122-126, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28945935

RESUMO

Acute coronary syndrome (ACS) is a dangerous and urgent clinical pattern of coronary artery disease. Aspirin and adenosine diphosphate P2Y12 receptor antagonists are the standard dual anti-platelet therapy for patients with ACS. Ticagrelor is a new oral antagonist of the adenosine diphosphate P2Y12 receptor. Randomized controlled trials (RCTs) have evaluated the efficacy and safety of ticagrelor compared to clopidogrel or prasugrel in patients with ACS, obtaining conflicting results. Thus, we conducted a meta-analysis of these RCTs to determine the efficacy and safety of ticagrelor in patients with ACS. Results of the meta-analysis indicate that ticagrelor decreased the risk of major adverse cardiovascular events (MACE) and all-cause death, but increased the risk of bleeding events. In Asiatic patients, analysis indicates that ticagrelor did not decrease the risk of MACE and all-cause death, while increasing the risk of bleeding events. Together, this meta-analysis suggests that ticagrelor was more effective, but less safe than clopidogrel and prasugrel in patients with ACS. Subgroup analysis indicates that ticagrelor was not more effective, although less safe than clopidogrel in Asiatic patients, thus more evidence is needed to further evaluate the efficacy and safety of ticagrelor in Asiatic patients.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Ticagrelor/efeitos adversos , Ticagrelor/uso terapêutico , Humanos
10.
J Phys Chem Lett ; 15(7): 1956-1961, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38346267

RESUMO

The study of molecular adsorption is crucial for understanding various chemical processes. Spectroscopy offers a convenient and non-invasive way of probing structures of adsorbed states and can be used for real-time observation of molecular binding profiles, including both structural and energetic information. However, deciphering atomic structures from spectral information using the first-principles approach is computationally expensive and time-consuming because of the sophistication of recording spectra, chemical structures, and their relationship. Here, we demonstrate the feasibility of a data-driven machine learning approach for predicting binding energy and structural information directly from vibrational spectra of the adsorbate by using CO adsorption on iron porphyrin as an example. Our trained machine learning model is not only interpretable but also readily transferred to similar metal-nitrogen-carbon systems with comparable accuracy. This work shows the potential of using structure-encoded spectroscopic descriptors in machine learning models for the study of adsorbed states of molecules on transition metal complexes.

11.
Microbiol Spectr ; 11(1): e0335022, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36633436

RESUMO

Rhizobia can infect legumes and induce the coordinated expression of symbiosis and defense genes for the establishment of mutualistic symbiosis. Numerous studies have elucidated the molecular interactions between rhizobia and host plants, which are associated with Nod factor, exopolysaccharide, and T3SS effector proteins. However, there have been relatively few reports about how the host plant recognizes the outer membrane proteins (OMPs) of rhizobia to mediate symbiotic nodulation. In our previous work, a gene (Mhopa22) encoding an OMP was identified in Mesorhizobium huakuii 7653R, whose homologous genes are widely distributed in Rhizobiales. In this study, a germin-like protein GLP1 interacting with Mhopa22 was identified in Astragalus sinicus. RNA interference of AsGLP1 resulted in a decrease in nodule number, whereas overexpression of AsGLP1 increased the number of nodules in the hairy roots of A. sinicus. Consistent symbiotic phenotypes were identified in Medicago truncatula with MtGLPx (refer to medtr7g111240.1, the isogeny of AsGLP1) overexpression or Tnt1 mutant (glpx-1) in symbiosis with Sinorhizobium meliloti 1021. The glpx-1 mutant displayed hyperinfection and the formation of more infection threads but a decrease in root nodules. RNA sequencing analysis showed that many differentially expressed genes were involved in hormone signaling and symbiosis. Taken together, AsGLP1 and its homology play an essential role in mediating the early symbiotic process through interacting with the OMPs of rhizobia. IMPORTANCE This study is the first report to characterize a legume host plant protein to sense and interact with an outer membrane protein (OMP) of rhizobia. It can be speculated that GLP1 plays an essential role to mediate early symbiotic process through interacting with OMPs of rhizobia. The results provide deeper understanding and novel insights into the molecular interactive mechanism of a legume symbiosis signaling pathway in recognition with rhizobial OMPs. Our findings may also provide a new perspective to improve the symbiotic compatibility and nodulation of legume.


Assuntos
Medicago truncatula , Rhizobium , Proteínas de Membrana/metabolismo , Simbiose , Rhizobium/metabolismo , Raízes de Plantas/metabolismo , Proteínas de Plantas/genética , Medicago truncatula/genética , Medicago truncatula/metabolismo
12.
Genes (Basel) ; 14(12)2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-38136929

RESUMO

Pseudomonas chengduensis is a new species of Pseudomonas discovered in 2014, and currently, there is a scarcity of research on this bacterium. The P. chengduensis strain WD211 was isolated from a fish pond. This study investigated the purification capability and environmental adaptability of strain WD211 in wastewater and described the basic features and functional genes of its complete genome. According to the results, the sewage treated with strain WD211 showed a decrease in concentration of 18.12% in total nitrogen, 89.39% in NH4+, 62.16% in NO3-, 79.97% in total phosphorus, and 71.41% in COD after 24 h. Strain WD211 is able to survive in a pH range of 6-11. It shows resistance to 7% sodium chloride and different types of antibiotics. Genomic analysis showed that strain WD211 may remove nitrogen and phosphorus through the metabolic pathway of nitrogen assimilation and phosphorus accumulation, and that it can promote organic decomposition through oxygenase. Strain WD211 possesses genes for producing betaine, trehalose, and sodium ion transport, which provide it with salt tolerance. It also has genes for antibiotic efflux and multiple oxidases, which give it antibiotic resistance. This study contributes to the understanding of the sewage treatment ability and potential applications of P. chengduensis.


Assuntos
Pseudomonas , Esgotos , Animais , Esgotos/microbiologia , Pseudomonas/genética , Pseudomonas/metabolismo , Aquicultura , Antibacterianos/metabolismo , Nitrogênio/metabolismo , Fósforo/metabolismo
13.
Comput Math Methods Med ; 2022: 1364985, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35941894

RESUMO

Background: Cardiovascular disease is a common disease with high prevalence, disability, and mortality. Exercise therapy can improve cardiac functional reserve and life quality of patients, but the benefits of different exercise intensities for cardiovascular patients are still controversial. In this study, literature search and meta-analysis were used to explore the effect of 2 intensities of exercise on the rehabilitation effect of cardiovascular patients. Methods: We searched Embase, Wiley online library, PubMed, Science Direct, and Clinicaltrials to look for randomized controlled trial (RCT) studies of high-intensity interval training (HIIT) versus moderate continuous training (MCT). After screening the inclusion criteria for the literature and assessing the risk of bias, a software analysis was performed using the R language toolkit to obtain forest plots and funnel maps. Results: 10 articles were included in this study into the quantitative analysis, and 520 patients participated in the study; meta-analysis results showed that after HIIT intervention, the VO2 peak index of patients was higher than that of the MCT group (MD = 1.39, 95% CI (0.10, 2.68), Z = 2.12, P = 0.0344), the peak heart rate HR peak was higher than that of the MCT training (MD = 7.71, 95% CI (5.12, 10.30), Z = 5.84, P < 0.0001), the respiratory exchange rate (maximum RER) was higher than that of the MCT training (MD = 0.02, 95% CI (0.00, 0.04), Z = 2.36, P = 0.0184), and the quality of life was higher than that of the MCT training (MD = 0.39, 95% CI (0.07, 0.71), Z = 2.40, P = 0.0165). Discussion. Compared with moderate continuous training, high intensity interval training is more conducive to improve the cardiopulmonary function of cardiovascular patients and improve their physical life quality.


Assuntos
Doenças Cardiovasculares , Treinamento Intervalado de Alta Intensidade , Doenças Cardiovasculares/terapia , Exercício Físico , Terapia por Exercício/métodos , Treinamento Intervalado de Alta Intensidade/métodos , Humanos , Qualidade de Vida
14.
Natl Sci Rev ; 9(10): nwac190, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36415316

RESUMO

The realization of automated chemical experiments by robots unveiled the prelude to an artificial intelligence (AI) laboratory. Several AI-based systems or robots with specific chemical skills have been demonstrated, but conducting all-round scientific research remains challenging. Here, we present an all-round AI-Chemist equipped with scientific data intelligence that is capable of performing basic tasks generally required in chemical research. Based on a service platform, the AI-Chemist is able to automatically read the literatures from a cloud database and propose experimental plans accordingly. It can control a mobile robot in-house or online to automatically execute the complete experimental process on 14 workstations, including synthesis, characterization and performance tests. The experimental data can be simultaneously analysed by the computational brain of the AI-Chemist through machine learning and Bayesian optimization, allowing a new hypothesis for the next iteration to be proposed. The competence of the AI-Chemist has been scrutinized by three different chemical tasks. In the future, the more advanced all-round AI-Chemists equipped with scientific data intelligence may cause changes to the landscape of the chemical laboratory.

15.
Int J Mol Med ; 44(2): 405-416, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173173

RESUMO

Hydroxysafflor Yellow A (HSYA) may reduce ischemia/reperfusion (I/R) injury. However, the underlying molecular mechanisms remain unclear. The present study explored the effect and the mechanisms of HSYA on myocardial injury in vivo and in vitro. Myocardial infarct size was assessed by Evans blue/2,3,5­triphenyltetrazoliumchloride staining. Levels of cardiac troponin I (cTnI), interleukin­6 (IL­6), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured using commercial kits. Alteration of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) generation was determined by fluorescent signals. Apoptosis was detected by terminal deoxynucleotidyl­transferase­mediated dUTP nick­end labeling staining, flow cytometry assay and caspase­3 activity. Expression levels of the apoptosis­associated proteins were detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. In vivo, animals treated with HSYA presented less severe myocardial injury and decreased janus kinase 2 (JAK2)/signal transducer and activator of transcription 1 (STAT1) activity, improved antioxidant capacity and decreased apoptosis. In vitro, compared with the hypoxia (H)/reoxygenation (R) + HSYA group, AG490 and S1491 treatment decreased the releases of cTnI, IL­6 and LDH and enhanced the resistance to oxidative stress by maintaining MMP and decreasing ROS generation. In addition, AG490 and S1491 were also identified to alleviate the H/R­induced apoptosis by inhibiting caspase 3 activity and modulating the expression levels of cleaved caspase­3, tumor necrosis factor receptor superfamily member 6 (Fas), Fas ligand, B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein. These data suggested that inactivation of the JAK2/STAT1 pathway strengthened the HSYA­induced protective effect in H/R­induced myocardial injury. In conclusion, the treatment of HSYA was effective in decreasing IR­induced myocardial injury, and this may be largely dependent on the JAK2/STAT1 pathway. Therefore, the present study provided a potential strategy to prevent myocardial I/R injury.


Assuntos
Chalcona/análogos & derivados , Janus Quinase 2/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Quinonas/uso terapêutico , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes/uso terapêutico , Chalcona/uso terapêutico , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Ratos Sprague-Dawley
16.
Mol Med Rep ; 18(4): 3649-3656, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30132539

RESUMO

Myocardial infarction (MI) is life­threatening and is generally accompanied by myocardial hypertrophy. Notably, Hydroxysafflor yellow A (HSYA) can prevent tissue injuries. The objective of this study was to investigate the effect of HSYA on hypertrophy after MI. Hematoxylin and eosin (H&E) staining assays were performed to measure cell area. The protein synthesis rate was assessed using the 3H Leucine incorporation assay. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR), western blot analysis and the immunohistochemical assay were used to detect the expression of target genes. The activity of superoxide dismutase (SOD), malondialdehyde (MDA) and the reactive oxygen species (ROS) generation were examined using commercial kits. Decreased myocardial hypertrophy was observed in animals treated with HSYA. Furthermore, the expression of nuclear factor (erythroid­derived 2)­like 2 (Nrf2) was higher in HSYA administration groups compared with that in the MI model group. In H9c2 cardiomyocytes, the pretreatment with HSYA increased the cell viability, however, it reduced protein synthesis rate, mitigated cell surface area and decreased the expression of Brain natriuretic factor (BNP) and ß­myosin heavy chain (ß­MHC). By contrast, the downregulation of Nrf2 deteriorated and reversed the effect of Ang II and HSYA. Furthermore, oxidative stress was alleviated by HSYA via inhibiting ROS generation, modulating the activities of SOD and MDA. In addition, the expression of NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase­1 (HO­1) were recovered by the pretreatment of HSYA that was combated by siNrf2. In conclusion, HSYA exerted anti­hypertrophic effects, which was pertinent with the activation of Nrf2/NQO­1/HO­1 signaling pathway. The findings of this study may inspire a novel strategy to combat MI.


Assuntos
Angiotensina II/metabolismo , Cardiomegalia/etiologia , Cardiomegalia/prevenção & controle , Chalcona/análogos & derivados , Infarto do Miocárdio/complicações , Substâncias Protetoras/uso terapêutico , Quinonas/uso terapêutico , Animais , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Linhagem Celular , Chalcona/farmacologia , Chalcona/uso terapêutico , Modelos Animais de Doenças , Heme Oxigenase-1/metabolismo , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/análise , Fator 2 Relacionado a NF-E2/metabolismo , Substâncias Protetoras/farmacologia , Quinonas/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
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