Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 757
Filtrar
Filtros adicionais











País/Região como assunto
Intervalo de ano
1.
Int J Mol Sci ; 20(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489906

RESUMO

Effector proteins secreted by plant pathogens play important roles in promoting colonization. Blumeria effector candidate (BEC) 1019, a highly conserved metalloprotease of Blumeria graminis f. sp. hordei (Bgh), is essential for fungal haustorium formation, and silencing BEC1019 significantly reduces Bgh virulence. In this study, we found that BEC1019 homologs in B. graminis f. sp. tritici (Bgt) and Gaeumannomyces graminis var. tritici (Ggt) have complete sequence identity with those in Bgh, prompting us to investigate their functions. Transcript levels of BEC1019 were abundantly induced concomitant with haustorium formation in Bgt and necrosis development in Ggt-infected plants. BEC1019 overexpression considerably increased wheat susceptibility to Bgt and Ggt, whereas silencing this gene using host-induced gene silencing significantly enhanced wheat resistance to Bgt and Ggt, which was associated with hydrogen peroxide accumulation, cell death, and pathogenesis-related gene expression. Additionally, we found that the full and partial sequences of BEC1019 can trigger cell death in Nicotiana benthamiana leaves. These results indicate that Bgt and Ggt can utilize BEC1019 as a virulence effector to promote plant colonization, and thus these genes represent promising new targets in breeding wheat cultivars with broad-spectrum resistance.

2.
PLoS Genet ; 15(8): e1008136, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31381575

RESUMO

The S-phase checkpoint plays an essential role in regulation of the ribonucleotide reductase (RNR) activity to maintain the dNTP pools. How eukaryotic cells respond appropriately to different levels of replication threats remains elusive. Here, we have identified that a conserved GSK-3 kinase Mck1 cooperates with Dun1 in regulating this process. Deleting MCK1 sensitizes dun1Δ to hydroxyurea (HU) reminiscent of mec1Δ or rad53Δ. While Mck1 is downstream of Rad53, it does not participate in the post-translational regulation of RNR as Dun1 does. Mck1 phosphorylates and releases the Crt1 repressor from the promoters of DNA damage-inducible genes as RNR2-4 and HUG1. Hug1, an Rnr2 inhibitor normally silenced, is induced as a counterweight to excessive RNR. When cells suffer a more severe threat, Mck1 inhibits HUG1 transcription. Consistently, only a combined deletion of HUG1 and CRT1, confers a dramatic boost of dNTP levels and the survival of mck1Δdun1Δ or mec1Δ cells assaulted by a lethal dose of HU. These findings reveal the division-of-labor between Mck1 and Dun1 at the S-phase checkpoint pathway to fine-tune dNTP homeostasis.

3.
J Clin Pharm Ther ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31436349

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Statins are widely used worldwide in the prevention and treatment of coronary atherosclerotic heart disease and ischaemic stroke. However, in clinical application, statins have shown great individual differences in terms of the efficacy and safety, some of which are related to genetic factors. The purpose of this article was to summarize the recent advances about the correlation between gene polymorphisms and the efficacy/safety of statins. METHODS: We searched the databases including PharmGKB and PubMed (published before June 2019) using the keywords such as 'statin', 'gene polymorphism' and 'SNP' and obtained more than 100 articles. In this review, we described the clinical studies of genetic variants associated with both the efficacy and adverse reactions of statins. We also clarified the importance of taking pharmacogenetic variation into account to improve the clinical application of statins. RESULTS AND DISCUSSION: The available data were collected and analysed to present the polymorphisms of candidate genes encoding the most promising proteins including SLCO1B1 (encoding uptake transporters); ABCB1, ABCC2, ABCG2 (encoding effluent transporter); APOE, APOA5 (encoding apolipoprotein); genes encoding cytochrome P450 enzyme system; KIF6, HMGCR, LDLR, LPA, PCSK9, COQ2, CETP, etc These genes were proved to be related to the pharmacodynamics and pharmacokinetics of statins, thus affecting the efficacy and safety. WHAT IS NEW AND CONCLUSION: In this paper, the correlation between gene polymorphisms and the efficacy/safety of statins was summarized. The authors reached a consensus that the variants of the genes encoding uptake and effluent transporters have the most effect on the efficacy/safety of statins. It pointed out that it is desirable to do genetic testing of these transporter genes to reduce the incidence of myopathy or to achieve better outcomes before patients use statins, especially in the regions with high frequency of risk allele.

4.
Sci Rep ; 9(1): 12141, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31413289

RESUMO

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

5.
FEBS Open Bio ; 9(9): 1640-1651, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31369204

RESUMO

Dysfunction of vascular endothelial cells often results in diabetic vascular complications. Circular RNAs (circRNAs) have been implicated in the pathogenesis of various diseases, including diabetes and many vascular diseases. This study aimed to explore the roles of circRNAs in high glucose-induced human umbilical vein endothelial cells (HUVECs) to elucidate the contributions of circRNAs to diabetic vascular complications. We subjected control and high glucose-induced HUVECs to RNA sequencing and identified 214 differentially expressed circRNAs (versus control HUVECs, fold change ≥ 2.0, P < 0.05). We then validated seven of these differentially expressed circRNAs by qPCR (hsa_circ_0008360, hsa_circ_0005741, hsa_circ_0003250, hsa_circ_0045462, hsa_circ_0064772, hsa_circ_0007976, and hsa_circ_0005263). A representative circRNA-microRNA (miRNA) network was constructed using the three most up-regulated circRNAs (hsa_circ_0008360, hsa_circ_0000109, and hsa_circ_0002317) and their putative miRNA. Bioinformatic analysis indicated that these circRNAs regulate the expressions of genes involved in vascular endothelial function and angiogenesis through targeting miRNAs. Our work highlights the potential regulatory mechanisms of three crucial circRNAs in diabetes-associated endothelial dysfunction.

6.
Microb Cell Fact ; 18(1): 138, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426823

RESUMO

BACKGROUND: The development of sustainable technologies for plant cell wall degradation greatly depends on enzymes with hydrolytic activities against carbohydrates. The waste by-products of agricultural cereals are important biomass sources because they contain large amounts of saccharides. Achieving efficient debranching and depolymerization are two important objectives for increasing the utilization of such renewable bioresources. GH51 α-L-arabinofuranosidases are important in biomass pretreatment because they act synergistically with other enzymes during hemicellulose hydrolysis. RESULTS: A GH51 α-L-arabinofuranosidase from Talaromyces leycettanus JCM12802 was heterologously expressed in Pichia pastoris GS115 and characterized. The recombinant α-L-arabinofuranosidase, TlAbf51, showed an optimum temperature and pH of 55-60 °C and 3.5-4.0, respectively, and remained stable at 50 °C and pH 3.0-9.0. TlAbf51 showed a higher catalytic efficiency (5712 mM-1 s-1) than most fungal α-L-arabinofuranosidases towards the substrate 4-nitrophenyl-α-L-arabinofuranoside. Moreover, TlAbf51 preferentially removed 1,2- or 1,3-linked arabinofuranose residues from arabinoxylan and acted synergistically with the bifunctional xylanase/cellulase TcXyn10A at an activity ratio of 5:1. The highest yields of arabinose and xylooligosaccharides were obtained when TlAbf51 was added after TcXyn10A or when both enzymes were added simultaneously. High-performance anion-exchange chromatography analyses showed that (i) arabinose and xylooligosaccharides with low degrees of polymerization (DP1-DP5) and (ii) arabinose and xylooligosaccharides (DP1-DP3) were the major hydrolysates obtained during the hydrolysis of sodium hydroxide-pretreated cornstalk and corn bran, respectively. CONCLUSIONS: In contrast to other fungal GH51 α-L-arabinofuranosidases, recombinant TlAbf51 showed excellent stability over a broad pH range and high catalytic efficiency. Moreover, TlAbf51 acted synergistically with another hemicellulase to digest arabino-polysaccharides. These favorable enzymatic properties make TlAbf51 attractive for biomass pretreatment and biofuel production.

7.
Opt Lett ; 44(17): 4359-4362, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31465402

RESUMO

The nonlinear frequency conversion of low-temporal-coherent light holds a variety of applications and has attracted considerable interest. However, its physical mechanism remains relatively unexplored, and the conversion efficiency and bandwidth are extremely insufficient. Here, considering the instantaneous broadband characteristics, we establish a model of second-harmonic generation (SHG) of a low-temporal-coherent pulse and reveal its differences from the coherent conditions. It is found that the second-harmonic spectrum distribution is proportional to the self-convolution of that of a fundamental wave. Because of this, we propose a method for realizing low-temporal-coherent SHG with high efficiency and broad bandwidth, and experimentally demonstrate a conversion efficiency up to 70% with a bandwidth of 3.1 THz (2.9 nm centered at 528 nm). To the best of our knowledge, this is the highest efficiency and broadest bandwidth of low-temporal-coherent SHG to date. Our research opens the door for the study of low-coherent nonlinear optical processes.

8.
J Neural Eng ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31398717

RESUMO

Abstract&#13; Objective.&#13; Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neurobehavioral disorders. Studies have tried to find the neural correlations of ADHD with electroencephalography (EEG). Due to the heterogeneity in the ADHD population, a multivariate EEG profile is useful, and the detection of a personalized abnormality in EEG is urgently needed. Deep learning algorithms, especially convolutional neural network (CNN), have made tremendous progress recently, and are expected to solve the problem. &#13; &#13; Approach.&#13; We adopted CNN techniques and a visualization technique named Gradient-weighted Class Activation Mapping (Grad-CAM) for detecting a personalized spatial-frequency abnormality in EEGs of ADHD children. A total of 50 children with ADHD (9 girls, mean age: 10.44±0.75) and 57 controls who were matched for age and handedness were recruited. The power spectrum density of EEGs was used as input. We presented an intuitive form of representing multichannel EEG data that is trainable to CNN models. Personalized abnormalities were derived from ADHD children and were compared to the distributions of relative powers in different frequency bands.&#13; &#13; Main results.&#13; We demonstrated that applying CNN techniques to ADHD identification is feasible, with an accuracy of 90.29±0.58%. There were major differences in personalized spatial-frequency abnormalities between individuals affected by ADHD. The abnormalities were consistent with the power distributions in both group- and individual- level. &#13; &#13; Significance.&#13; This study provided a novel method for detecting personalized spatial-frequency abnormalities of children with ADHD at a precise spatial-frequency resolution. We proposed a new form of representation of multichannel EEG data that is compatible with mainstream CNN architectures. We ensured that CNN models were interpretable and reliable relating to clinical practice by visualizing the decision-making process. We expect that detection of personalized abnormalities using deep learning techniques can facilitate the identification of potential neural pathways and the planning of targeted treatments for children with ADHD.

9.
ACS Appl Mater Interfaces ; 11(29): 26460-26466, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31267730

RESUMO

Negative exchange bias is usually discovered in ferromagnetic (FM)/antiferromagnetic (AFM) heterostructures after a field-cooling (FC) process. Relatively, positive exchange bias (PEB) is a rarely observed phenomenon. So far, almost all of the models for PEB whether undergoing FC or zero-field-cooling (ZFC) treatment have been explained by an interaction of strong AFM coupling at the interface. In this work, by selecting a special material of SrFeO3-x as the AFM layer, coupled with FM-La0.7Sr0.3MnO3 (LSMO), we obtain a novel PEB effect of the bilayer after ZFC measurement, of which the shift directions are unfixable and dependent on the initial magnetization direction. Based on a transient magnetic field to control the remanence (Mr) direction of LSMO at room temperature and then cooling below the TN of SrFeO3-x without any magnetic field disturbance, the shift direction can be locked only toward the transient magnetic field. Combined with experimental results and first-principles calculations, we propose that the above phenomena are explained as the field-induced AFM phase of SrFeO3-x transforming into the FM phase at an FM coupling bilayer interface. Thus, our finding may provide a new approach to realize and tune the zero-field-cooling PEB with FM coupling heterostructures.

10.
Sci Rep ; 9(1): 10335, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31316132

RESUMO

Multiple lines of evidence have shown that systemic lupus erythematosus (SLE) is attributable to both genetic and environmental factors. The product of GRB2 is a key factor in the activation of B cells and has been reported to be significantly associated with SLE in European populations. In the study, we aimed to investigate the relationship between GRB2 and SLE. A total of 1,710 Han Chinese women comprising 567 SLE patients and 1,143 controls were recruited to genotype 20 selected tagging SNPs. We tested the potential association between 13 clinical variables of SLE and the significant polymorphisms related to SLE. The eQTL data were extracted from the GTEx database to examine the functional consequences of the targeted SNPs. A significant association signal was identified between rs36023980 and SLE in both genotypic and allelic analyses (OR = 0.61, P = 0.0003). Complement inhibition was shown to be significantly associated with the genotypes of SNP rs36023980 in SLE patients (Pgenotype = 0.003). Further stratification analyses showed that the genetic association signal of SNP rs36023980 on SLE could only be identified in cases with complement inhibition. SNP rs36023980 was also identified to be significantly associated with the expression of GRB2 in whole blood and sun-exposed skin. In conclusion, our findings confirm the results from the previous GWAS and are the first to report the association of GRB2 with SLE in Han Chinese population.

11.
Int J Biol Macromol ; 137: 160-168, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31255623

RESUMO

The rheological properties and emulsifying behavior of four polysaccharides (HBSS, CHSS, DASS, and CASS) sequentially extracted from Amana edulis (AEPs) were investigated under various concentrations, temperatures, pH levels, and ionic strengths. The apparent viscosity of the four AEPs solutions at 1% (w/w) concentration were found to be CHSS > DASS > HBSS > CASS. When the AEPs were heated to 100 οC, they showed lower colloidal viscosity, whereas after refrigeration and chilling, higher apparent viscosities were observed. The apparent viscosity of four AEPs at pH 10 or pH 4 was lower than that at pH 7. The apparent viscosity increased at a lower sodium ion concentration and then declined with an increase in ion concentration. The storage modulus (G') and loss modulus (G″) increased with an increase in oscillation frequency. The emulsifying activity and stability were enhanced as the concentration of the four AEPs increased. The emulsifying activity and stability of the AEPs were steady within the pH range of 2-10 and NaCl concentration range of 0-0.4 mol/L. Our results implied that these polysaccharides can be utilized as a novel hydrocolloid source for natural thickeners in the food industry.

12.
J Nat Prod ; 82(8): 2067-2077, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31310122

RESUMO

Fungal drug resistance is a major health threat, and reports of clinical resistance worldwide are becoming increasingly common. In a research program to discover new molecules to help overcome this problem, 14 new lanostane-type triterpenoids, gibbosicolids A-G (2-8) and gibbosic acids I-O (9-15), were isolated from the fruiting bodies of Ganoderma gibbosum, along with seven known triterpenoid derivatives. These compounds featured high levels of oxidation, epimerization, and γ-lactonization. Structures were elucidated by comprehensive spectroscopic analyses and HRMS data. Absolute configurations were assigned based on quantum chemical calculations, including calculated chemical shift with DP4+ analysis, coupling constants, and electronic circular dichroism (ECD) methods. Results show that the calculated NMR with DP4+ analysis could not reliably establish the overall spatial configuration of molecules possessing independent and free-rotational stereoclusters. All these compounds significantly increased the sensitivity of fluconazole (FLC)-resistant C. albicans to FLC. Compounds 2, 5, 9, 12, 16, 17, and 21 exhibited strong antifungal activity against FLC-resistant C. albicans when combined with FLC, with MIC50 values ranging from 3.8 to 8.8 µg/mL.

14.
J Neuroinflammation ; 16(1): 119, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171009

RESUMO

After the publication of the original article [1], it came to the authors' attention that there was an error in the originally published version of Fig. 5b. The image of CD4+CD25+ T cells of the statin-Dex group was unintentionally replaced with the image of CD4+CD25+ T cells from the control group. The correct version of Fig. 5b is published in this Erratum.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31180828

RESUMO

OBJECTIVE: Direct interaction between the brain and muscle is significant for investigating the oscillation mechanisms in the motor control system. To our knowledge, the partial directed coherence (PDC) method is sufficient to reflect the direct interaction among multivariate time series in the frequency domain, but fails to eliminate the spectral overlap among frequency bands. Therefore, we expanded the PDC method and constructed a novel method, named variational-mode-decomposition-based PDC (VMDPDC), to describe the direct interaction on specific frequency bands. To verify this, we made a comparison with the Granger causality (GC), PDC and FIR-based PDC (FIRPDC) methods in two numerical models (bivariate coupling model and multivariate coupling model). After that, we applied this method to analyze the functional corticomuscular coupling (FCMC) during steady-state grip task. Simulation results showed that, compared with the GC, PDC and FIRPDC methods, the VMDPDC method could accurately detect the direct interaction on specific frequency bands. The results on experimental data showed that the direct interaction in FCMC mainly focused on the alpha (8-15 Hz), beta (15-35 Hz) and gamma (35-60 Hz) bands. Further analysis demonstrated that the coupling strength in descending direction was significantly higher than that in the opposite direction. Both simulation and experimental results indicated that the proposed method could effectively describe the direct interaction on specific frequency bands. This study also provides a theoretical foundation for further exploration on the mechanism of the motor control.

16.
Clin Neurophysiol ; 130(8): 1235-1242, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31163368

RESUMO

OBJECTIVE: The objective of this study was to explore the role for quadratic phase coupling within electroencephalography (EEG) oscillations in the diagnosis of consciousness and consciousness restoration for disorders of consciousness (DOC). METHODS: Fifty-one DOC patients were enrolled in this study. For each patient, a Coma Recovery Scale-Revised (CRS-R) score and 20-min resting-state EEG were recorded. Consciousness recovery was assessed with a CRS-R score at a three-month follow-up. Twenty healthy subjects were included as controls. General harmonic wavelet transform-based bicoherence was used to quantify the quadratic phase coupling characteristics of the EEG oscillations. RESULTS: Quadratic phase self-coupling (QPSC) at the delta (QPSC_delta), theta (QPSC_theta) and alpha (QPSC_alpha) bands were closely correlated with patient CRS-R scores. Particularly, the QPSC_theta value could significantly differentiate between vegetative state (VS) patients, minimally conscious state (MCS) patients and healthy control subjects. As compared to VS patients, patients with MCS had a lower QPSC_theta value on the left as well as a higher QPSC_alpha value in right frontal regions. The frontal QPSC_theta value showed significant differences between recovered and unrecovered patients. CONCLUSION: QPSC characteristics could differentiate between consciousness states and show a predictive ability for the recovery of consciousness in DOC patients. SIGNIFICANCE: Changes in QPSC accompany consciousness injury and restoration in DOC patients. A QPSC assessment is helpful in the diagnosis and prognosis of DOC patients.

17.
Int J Neurosci ; : 1-6, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31232139

RESUMO

Objective: To make comparative studies on the effects of different doses of atorvastatin combined with aspirin on inflammatory cytokines, blood lipids, blood glucose, other biochemical indexes and carotid plaques in patients with ischemic cerebrovascular disease (ICVD) and carotid plaques. Method: One hundred and twenty patients with ICVD and carotid plaques admitted by Renmin Hospital, Hubei University of Medicine Hospital from December 2016 to December 2017 were selected and randomly divided into experimental group and control group, 60 cases in each group. Patients in the control group was asked to orally take standard dose of atorvastatin (20 mg/d) combined with aspirin enteric-coated tablets (100 mg/d). Patients in the experimental group was asked to orally take high-dose atorvastatin (40 mg/d) combined with the same amount of aspirin enteric-coated tablets. Patients in two groups were treated for 6 months averagely. The levels of inflammatory factors, changes in blood biochemical parameters and carotid plaque degrees of patients in two groups before and after treatment were inspected and compared. Results: The levels of serum high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF-a), interleukin-6 (IL-6) and homocysteine (Hcy) in patients of the experimental group after treatment were higher than those in the control group, difference with statistical significance (p < .05). The total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) in patients of the experimental group after treatment were lower than those in the control group and before treatment. The high-density lipoprotein cholesterol (HDL-C) was higher than that of the control group and before treatment, the levels of fasting blood glucose (FBS) and glycosylated hemoglobin (HbAIc) in patients of the experimental group significantly increased compared to those before treatment, difference with statistical significance (p < .05). There was no significant change in the control group. The carotid intima-media thickness (IMT) and plaque area in patients of the experimental group were lower than those in the control group and before treatment, difference with statistical significance (p < .05). Conclusion: High-dose atorvastatin combined with aspirin for treatment of patients with ICVD can effectively reduce inflammatory inflammatory cytokine levels in serum and reduce IMT and carotid plaque area. With more obvious effect than lower dose of atorvastatin combined with aspirin, it is easy to cause blood glucose abnormality. So, it is necessary to pay attention to monitoring blood sugar during medication period.

18.
CNS Neurosci Ther ; 2019 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-31228356

RESUMO

BACKGROUND: Autism spectrum disorder (ASD) is a very complex neurodevelopmental disorder, characterized by social difficulties and stereotypical or repetitive behavior. Some previous studies using low-frequency repetitive transcranial magnetic stimulation (rTMS) have proven of benefit in ASD children. METHODS: In this study, 32 children (26 males and six females) with low-function autism were enrolled, 16 children (three females and 13 males; mean ± SD age: 7.8 ± 2.1 years) received rTMS treatment twice every week, while the remaining 16 children (three females and 13 males; mean ± SD age: 7.2 ± 1.6 years) served as waitlist group. This study investigated the effects of rTMS on brain activity and behavioral response in the autistic children. RESULTS: Peak alpha frequency (PAF) is an electroencephalographic measure of cognitive preparedness and might be a neural marker of cognitive function for the autism. Coherence is one way to assess the brain functional connectivity of ASD children, which has proven abnormal in previous studies. The results showed significant increases in the PAF at the frontal region, the left temporal region, the right temporal region and the occipital region and a significant increase of alpha coherence between the central region and the right temporal region. Autism Behavior Checklist (ABC) scores were also compared before and after receiving rTMS with positive effects shown on behavior. CONCLUSION: These findings supported our hypothesis by demonstration of positive effects of combined rTMS neurotherapy in active treatment group as compared to the waitlist group, as the rTMS group showed significant improvements in behavioral and functional outcomes as compared to the waitlist group.

19.
BMC Endocr Disord ; 19(1): 59, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182088

RESUMO

BACKGROUND: The present study aimed to investigate the inhibitory effects of aminoguanidine (AG) and 2-bromoethylamine (2-BEA) on the semicarbazide-sensitive amine oxidase (SSAO) activity both in vitro and in vivo, and the prevention role of AG and 2-BEA in the morphology of aorta and kidney in diabetic rats. METHODS: The aortic homogenates isolated from Sprague-Dawley (SD) rats were treated with different concentrations of AG or 2-BEA to investigate the inhibitory effects on the SSAO activity in vitro, using benzylamine as the substrate. In addition, 65 male SD rats were randomly assigned into normal control (NC) (n = 10), NC + AG (n = 10), NC + 2-BEA (n = 10) and diabetes mellitus (DM) model groups (n = 35). Type 1 diabetic rat model was induced by intraperitoneal injection of 1% streptozotocin-sodium citrate buffer 55 mg/kg. After establishing the diabetic rat model by a single intraperitoneal injection of streptozotocin. Except those failed in modeling, 30 rats in the DM model group were further randomly divided into the DM, DM + AG, DM + 2-BEA groups (n = 10 in each). Rats in the DM + AG and NC + AG group were intraperitoneally injected with AG (25 mg/kg),those in the DM + 2-BEA and NC + 2-BEA group were administered with 2-BEA (20 mg/kg) daily for eight weeks. After eight weeks of treatment, the SSAO activity in the plasma and aorta, and plasma levels of formaldehyde (FA) and methylamine (MA) were measured by high performance liquid chromatograph. Radioimmunoassay was used to determine the plasma endothelin-1 (ET-1) concentration, while nitric acid deoxidized enzyme method was performed to detect the plasma nitrate/nitrite (NO(x)-) level. Besides, the morphological changes of aorta and kidney tissues were examined by optical and electron microscopes. RESULTS: Both AG and 2-BEA exerted strong inhibitory effect on the aortic SSAO activity in vitro, with the IC50 values of 12.76 µmol/L and 3.83 µmol/L, respectively. Compared with the NC group, the SSAO activity in the plasma and aorta, and plasma levels of MA and ET-1 were significantly increased (P < 0.01), whereas the plasma NO(x)- level was obviously lower in the DM group (P < 0.01). A significantly decreased SSAO activity and plasma ET-1 level, as well as obviously increased plasma levels of MA and NO(x)- were observed in the DM + AG and DM + 2-BEA groups in comparison with the DM group (P < 0.01). However, there was no significant difference in plasma FA concentration among all the groups. Besides, the morphological changes of aorta and kidney were apparently alleviated in the DM + AG and DM + 2-BEA groups as compared with the DM group. CONCLUSIONS: Both AG and 2-BEA can inhibit the SSAO activity in the plasma and aorta. Moreover, the inhibitory effects of AG and 2-BEA on the SSAO-mediated oxidative deamination had great benefit in the morphological changes of aorta and kidney in diabetic rats.

20.
J Cell Physiol ; 234(12): 23495-23506, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31173361

RESUMO

Mitochondrial fusion is linked to heart and liver ischemia-reperfusion (IR) insult. Unfortunately, there is no report to elucidate the detailed influence of mitochondrial fusion in renal IR injury. This study principally investigated the mechanism by which mitochondrial fusion protected kidney against IR injury. Our results indicated that sirtuin 3 (Sirt3) was inhibited after renal IR injury in vivo and in vitro. Overexpression of Sirt3 improved kidney function, modulated oxidative injury, repressed inflammatory damage, and reduced tubular epithelial cell apoptosis. The molecular investigation found that Sirt3 overexpression attenuated IR-induced mitochondrial damage in renal tubular epithelial cells, as evidenced by decreased reactive oxygen species production, increased antioxidants sustained mitochondrial membrane potential, and inactivated mitochondria-initiated death signaling. In addition, our information also illuminated that Sirt3 maintained mitochondrial homeostasis against IR injury by enhancing optic atrophy 1 (OPA1)-triggered fusion of mitochondrion. Inhibition of OPA1-induced fusion repressed Sirt3 overexpression-induced kidney protection, leading to mitochondrial dysfunction. Further, our study illustrated that OPA1-induced fusion could be affected through ERK; inhibition of ERK abolished the regulatory impacts of Sirt3 on OPA1 expression and mitochondrial fusion, leading to mitochondrial damage and tubular epithelial cell apoptosis. Altogether, our results suggest that renal IR injury is closely associated with Sirt3 downregulation and mitochondrial fusion inhibition. Regaining Sirt3 and/or activating mitochondrial fission by modifying the ERK-OPA1 cascade may represent new therapeutic modalities for renal IR injury.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA