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1.
Nucleic Acids Res ; 2024 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-39470702

RESUMO

Single nucleotide variants (SNVs), as important components of genetic variation, affect gene expression, function and phenotype. Mining and summarizing the spatial distribution of SNVs in diseased and normal tissues for a better understanding of their characteristics and potential roles in cell-lineage determination, aging, or disease occurrence is significant. Herein, we have developed a comprehensive spatial mutation resource stSNV (http://bio-bigdata.hrbmu.edu.cn/stSNV/index.jsp), which provides an atlas of spatial SNVs in major diseased and normal tissues of human and mouse. stSNV documents 42 202 spatial mutated genes involving 898 908 SNVs called from 730 067 spots within 450 slices from 19 diseased and 28 normal tissues. Importantly, potential characteristics of SNVs are explored and provided by analyzing the perturbation of the SNVs to gene expression, spatial communication, biological function, region-specific mutated genes, spatial mutant signatures, SNV-cell co-localization and mutation core region. All these spatial mutation data and in-depth analyses have been integrated into a user-friendly interface, visualized through intuitive tables and various image formats. Flexible tools are developed to explore co-localization among clusters, genes, cell types and SNVs in the same slice. In summary, stSNV as a valuable resource helps to dissect intra-tissue genetic heterogeneity and lays the groundwork for understanding the SNVs' biological regulatory mechanisms.

2.
Mol Cell Biochem ; 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38880861

RESUMO

Acute myocardial infarction is mainly caused by a lack of blood flood in the coronary artery. Angiopoietin-like protein 2 (ANGPTL2) induces platelet activation and thrombus formation in vitro through binding with immunoglobulin-like receptor B, an immunoglobulin superfamily receptor. However, the mechanism by which it regulates platelet function in vivo remains unclear. In this study, we investigated the role of ANGPTL2 during thrombosis in relationship with ST-segment elevation myocardial infarction (STEMI) with spontaneous recanalization (SR). In a cohort of 276 male and female patients, we measured plasma ANGPTL2 protein levels. Using male Angptl2-knockout and wild-type mice, we examined the inhibitory effect of Angptl2 on thrombosis and platelet activation both in vivo and ex vivo. We found that plasma and platelet ANGPTL2 levels were elevated in patients with STEMI with SR compared to those in non-SR (NSR) patients, and was an independent predictor of SR. Angptl2 deficiency accelerated mesenteric artery thrombosis induced by FeCl3 in Angptl2-/- compared to WT animals, promoted platelet granule secretion and aggregation induced by thrombin and collogen while purified ANGPTL2 protein supplementation reversed collagen-induced platelet aggregation. Angptl2 deficiency also increased platelet spreading on immobilized fibrinogen and clot contraction. In collagen-stimulated Angptl2-/- platelets, Src homology region 2 domain-containing phosphatase (Shp)1-Y564 and Shp2-Y580 phosphorylation were attenuated while Src, Syk, and Phospholipase Cγ2 (PLCγ2) phosphorylation increased. Our results demonstrate that ANGPTL2 negatively regulated thrombus formation by activating ITIM which can suppress ITAM signaling pathway. This new knowledge provides a new perspective for designing future antiplatelet aggregation therapies.

3.
BMC Med Imaging ; 24(1): 53, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429683

RESUMO

BACKGROUND: The diameter of the ostial and proximal left main coronary artery can be greater than 5.0 mm. However, the diameters of the mostly available coronary drug-eluting stents (DESs) are ≤ 4.0 mm. Whether high-pressure dilatation can increase the diameter of stents from 4.0 to 5.0 mm and whether post-dilatation leads to longitudinal stent deformation (LSD) of 4.0-mm-diameter stents have rarely been studied. Therefore, this study aims to evaluate LSD and stent malapposition of six types of commercially available 4.0-mm-diameter stents in China in a 5.0-mm-diameter artificial blood vessel model by optical coherence tomography (OCT) in vitro. METHODS: The left main coronary artery was simulated by a truncated cone-shaped silicone tube. The internal diameters were 4.0 mm at one end of the silicone tube and 5.0 mm at the other end. Six different types of coronary stents widely used in China were selected for this study. Each stent was respectively implanted into the simulated blood vessel and dilated to a diameter of 4.2 mm according to the stent-balloon pressure compliance table. The stents were subjected to post-dilatation with a 5.0 × 15-mm noncompliant balloon. The LSD ratio of the longitudinal axis of each stent and stent malapposition were measured through OCT, and any fractures of the stents were determined. RESULTS: None of the six types of stents fractured following post-dilatation. The longitudinal axes of the BuMA and Excrossal stents were slightly shortened, while the other stents were elongated after high-pressure post-dilatation. All stents expanded to a diameter of 5.0 mm without incomplete stent apposition, except for the Nano Plus stent, which remained malapposed after high-pressure post-dilatation. CONCLUSION: All 4.0-mm-diameter stents can be expanded to a diameter of 5.0 mm by noncompliant balloon post-dilatation without stent strut fracture. Most stents were found to be well apposed after high-pressure post-dilatation. However, LSD was observed after post-balloon dilatation. Stent malapposition might be positively correlated with the percentage change in stent length.


Assuntos
Stents , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Dilatação , Stents/efeitos adversos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Silicones
4.
Entropy (Basel) ; 25(6)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37372233

RESUMO

In complex industrial environments, the vibration signal of the rolling bearing is covered by noise, which makes fault diagnosis inaccurate. In order to overcome the effect of noise on the signal, a rolling bearing fault diagnosis method based on the WOA-VMD (Whale Optimization Algorithm-Variational Mode Decomposition) and the GAT (Graph Attention network) is proposed to deal with end effect and mode mixing issues in signal decomposition. Firstly, the WOA is used to adaptively determine the penalty factor and decomposition layers in the VMD algorithm. Meanwhile, the optimal combination is determined and input into the VMD, which is used to decompose the original signal. Then, the Pearson correlation coefficient method is used to select IMF (Intrinsic Mode Function) components that have a high correlation with the original signal, and selected IMF components are reconstructed to remove the noise in the original signal. Finally, the KNN (K-Nearest Neighbor) method is used to construct the graph structure data. The multi-headed attention mechanism is used to construct the fault diagnosis model of the GAT rolling bearing in order to classify the signal. The results show an obvious noise reduction effect in the high-frequency part of the signal after the application of the proposed method, where a large amount of noise was removed. In the diagnosis of rolling bearing faults, the accuracy of the test set diagnosis in this study was 100%, which is higher than that of the four other compared methods, and the diagnosis accuracy rate of various faults reached 100%.

5.
Biochem Biophys Res Commun ; 614: 145-152, 2022 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-35597151

RESUMO

Liver-X-receptor (LXR) has previously been shown to exert a cardioprotective effect against the development of diabetic cardiomyopathy (DCM) associated with a reduction in mitochondrial dysfunction. However, the underlying mechanism by which LXR activation attenuates the structural and functional mitochondrial impairments caused by high glucose (HG) stress remains unclear. We demonstrate here that LXR activation inhibits HG stress-induced mitochondrial dysfunction and ameliorates aberrant mitochondrial dynamics. Furthermore, LXR activation regulates mitochondrial dynamics by inhibiting HG stress-induced upregulation of Calpain1 expression. These data indicate that amelioration of Calpain1-mediated aberrant mitochondrial dynamics may be at least part of the mechanism underlying the cardioprotective effects of LXR against HG stress. Therefore, LXR is a potentially attractive molecular target for treating cardiac mitochondrial dysfunction in patients with diabetes.


Assuntos
Calpaína , Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Glucose , Receptores X do Fígado , Dinâmica Mitocondrial , Animais , Apoptose , Calpaína/genética , Calpaína/metabolismo , Diabetes Mellitus Experimental/metabolismo , Cardiomiopatias Diabéticas/metabolismo , Regulação para Baixo , Glucose/metabolismo , Receptores X do Fígado/genética , Receptores X do Fígado/metabolismo , Dinâmica Mitocondrial/genética , Dinâmica Mitocondrial/fisiologia , Miócitos Cardíacos/metabolismo , Estresse Oxidativo , Ratos
6.
Environ Res ; 210: 113015, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35219630

RESUMO

Using artificial intelligence method to describe general working process is a more meaningful and widely used idea in various practical projects. At the same time, it is also an important way to realize intelligent management. Water pollution is serious all over the world, also the intelligent management of sewage treatment has always been one of the urgent problems to be solved. For this, an intelligent management system is designed in this study to realize automatic monitoring and intelligent decision-making of sewage treatment. However, the existing technology usually trains artificial intelligence models based on historical data, and such models have some limitations in describing nonlinear and complex wastewater treatment processes. Offline machine learning lacks dynamic adaptive characteristics to scene changes. Considering this, this paper designs an online learning-empowered smart management for A2/O process in sewage treatment processes (OL-AP). Online learning is based on the new data generated by the scene transformation, so that the model can learn again and give better results. In this study, relevant simulation experiments are carried out on the sewage treatment data of a sewage treatment plant in Chongqing. Firstly, automatic data collection is realized based on the sensor network of the IoT. Then, according to the preprocessed data, the designed prediction model is trained and a set of parameters with better evaluation indexes is obtained. Finally, online learning uses the latest data samples based on the online feedback of real scenes to optimize the model by retraining and adjusting parameters.


Assuntos
Inteligência Artificial , Educação a Distância , Inteligência , Aprendizado de Máquina , Esgotos
7.
Chem Biodivers ; 19(8): e202200252, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35831709

RESUMO

Chrysanthemum originates in China and has been cultivated for tea and food utilizations over two thousand years. According to differences in origin and processing methods, Chrysanthemum morifolium Ramat. can be categorized into many cultivars. This study aims to investigate the chemical components in chrysanthemum and clarify similarities and differences between different chrysanthemum varieties. A total of 55 non-volatile components and 66 volatile components in chrysanthemum were identified by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and gas chromatography-mass spectrometry (GC/MS) methods, respectively. A rapid UPLC-MS/MS method was developed and validated for the simultaneous determination of 13 active components in 30 batches chrysanthemum samples of ten different cultivars. Multivariate statistical techniques were applied to analyze the samples. The result indicated that Boju, Huaiju and Chuju were more similar in terms of the ingredient content and Qiju, Jinsihuangju, Huangju, Hangju, Gongju, Fubaiju, Baiju have a high degree of similarity. Furthermore, isochlorogenic acid C, luteolin, apigenin-7-glucoside, chlorogenic acid, apigenin and cryptochlorogenic acid plays an important role in distinguishing different varieties of chrysanthemum. The established strategy explains the similarities and differences between different varieties of chrysanthemums to some extent, and provides certain reference value for the choice of chrysanthemums for eating or medicinal purposes in daily life.


Assuntos
Chrysanthemum , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Chrysanthemum/química , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas em Tandem
8.
Molecules ; 28(1)2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36615527

RESUMO

The environmentally benign Fe2(MoO4)3 plays a crucial role in the transformation of organic contaminants, either through catalytically decomposing oxidants or through directly oxidizing the target pollutants. Because of their dual roles and the complex surface chemical reactions, the mechanism involved in Fe2(MoO4)3-catalyzed PDS activation processes remains obscure. In this study, Fe2(MoO4)3 was prepared via the hydrothermal and calcine method, and photoFenton degradation of methyl orange (MO) was used to evaluate the catalytic performance of Fe2(MoO4)3. Fe2(MoO4)3 catalysts with abundant surface oxygen vacancies were used to construct a synergistic system involving a photocatalyst and PDS activation. The oxygen vacancies and Fe2+/Fe3+ shuttle played key roles in the novel pathways for generation of •O2-, h+, and 1O2 in the UV-Vis + PDS + FMO-6 photoFenton system. This study advances the fundamental understanding of the underlying mechanism involved in the transition metal oxide-catalyzed PDS activation processes.


Assuntos
Óxidos , Oxigênio , Catálise
9.
Molecules ; 27(24)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36557777

RESUMO

In order to improve the catalytic activity of cobalt molybdate (CoMoO4), a PDS-activated and UV-vis assisted system was constructed. CoMoO4 was prepared by coprecipitation and calcination, and characterized by XRD, FTIR, Raman, SEM, TEM, XPS, TGA Zeta potential, BET, and UV-Vis DRS. The results showed that the morphology of the CoMoO4 nanolumps consisted of stacked nanosheets. XRD indicated the monoclinic structures with C2/m (C32h, #12) space group, which belong to α-CoMoO4, and both Co2+ and Mo6+ ions occupy distorted octahedral sites. The pH of the isoelectric point (pHIEP) of CMO-8 at pH = 4.88 and the band gap of CoMoO4 was 1.92 eV. The catalytic activity of CoMoO4 was evaluated by photo-Fenton degradation of Congo red (CR). The catalytic performance was affected by calcination temperature, catalyst dosage, PDS dosage, and pH. Under the best conditions (0.8 g/L CMO-8, PDS 1 mL), the degradation efficiency of CR was 96.972%. The excellent catalytic activity of CoMoO4 was attributed to the synergistic effect of photo catalysis and CoMoO4-activated PDS degradation. The capture experiments and the ESR showed that superoxide radical (·O2-), singlet oxygen (1O2), hole (h+), sulfate (SO4-·), and hydroxyl (·OH-) were the main free radicals leading to the degradation of CR. The results can provide valuable information and support for the design and application of high-efficiency transition metal oxide catalysts.


Assuntos
Vermelho Congo , Água , Peróxido de Hidrogênio/química , Óxidos/química , Cobalto/química , Catálise
10.
Rev Cardiovasc Med ; 22(3): 1009-1017, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34565102

RESUMO

The aim of this study was to investigate the correlation between v-set and transmembrane domain-containing 1 (VSTM1) expression and incidence of major adverse cardiac events (MACE) in patients with coronary heart disease (CHD). A total of 310 patients were divided into a non-acute coronary syndrome (non-ACS) group (containing the stable angina group, and the asymptomatic coronary artery diseaseand other patients group) and an ACS group (containing unstable angina and acute myocardial infarction patients). Monocytic VSTM1 expression levels (assessed via average fluorescence intensity derived from antibody binding to VSTM1) in each group were detected and analyzed. The cut-off value of monocytic VSTM1 expression to predict the onset of ACS and MACE was confirmed. VSTM1 expression in monocytes from the ACS group was lower than that of the non-ACS group. The incidence of MACEs in the high VSTM1-expression group was much less than that of those in the low VSTM1 expression group at the 1 year follow-up stage. VSTM1 expression had an independent-inversed association with increased incidence of MACE and ACS. VSTM1 expression in monocytes may help to predict the occurrence of ACS in patients with CHD, and moreover it may provide the means to evaluate MACE prognosis during CHD patient follow-up.


Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Infarto do Miocárdio , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Humanos , Monócitos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Prognóstico , Fatores de Risco
11.
Transgenic Res ; 30(6): 739-750, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34347236

RESUMO

Our study was aimed to investigate the effects of lgals3a (Gal-3 encoding gene) on the development of zebrafish embryo and its underlying mechanisms. Morpholino (MO) technology was used to inhibit the expression of zebrafish lgals3a, and the effect of lgals3a gene knockdown on zebrafish embryo development and the number of monocyte macrophages was observed. Effect of lgals3a-e3i3-MO on apoptosis of zebrafish was detected by acridine orange staining. In addition, the mRNA expression levels of Wnt/ß-catenin signaling pathway-related genes were detected by RT-qPCR. Compared with control-MO group, the zebrafish embryos injected with lgals3a-e3i3-MO had obvious defects in the head, eyes, and tail, and pericardial edema. Lgals3a-e3i3-MO significantly reduced the number of mononuclear macrophages in zebrafish embryos compared with the control-MO group. The results of acridine orange staining showed that compared with the control-MO group, lgals3a-e3i3-MO promoted cardiomyocyte apoptosis in zebrafish. Furthermore, lgals3a-e3i3-MO significantly up-regulated the expression of dkk1b, wnt9a, lrp5, fzd7a, ß-catenin, Gsk-3ß, mycn, myca in the Wnt/ß-catenin pathway, and decreased the expression of lef1. These results indicate that lgals3a-e3i3-MO inhibits zebrafish embryo development, reduces the number of mononuclear macrophages, activates Wnt/ß-catenin signaling pathway and promotes cardiomyocyte apoptosis.


Assuntos
Peixe-Zebra , beta Catenina , Laranja de Acridina/metabolismo , Laranja de Acridina/farmacologia , Animais , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicogênio Sintase Quinase 3 beta/farmacologia , Receptores de Superfície Celular , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Proteínas Wnt/farmacologia , Via de Sinalização Wnt/genética , Proteínas de Peixe-Zebra/genética , beta Catenina/genética , beta Catenina/metabolismo
12.
BMC Cardiovasc Disord ; 21(1): 343, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34266394

RESUMO

BACKGROUND: Serum free fatty acid (FFA) concentrations are associated with coronary heart disease and diabetes mellitus (DM). Few studies focused on the relationship between serum FFA levels and coronary artery calcification (CAC). METHODS: This was a retrospective, single-centered study recruiting patients underwent FFA quantification, coronary angiography and intravascular ultrasound (IVUS). CAC severity was assessed with the maximum calcific angle (arc) of the calcified plaque scanned by IVUS. Patients with an arc ≥ 180° were classified into the severe CAC (SCAC) group, and those with an arc < 180° were classified into the non-SCAC group. Clinical characteristics, serum indices were compared between 2 groups. Logistic regression, receiver operating characteristic (ROC) curves and area under the curves (AUC) were performed. RESULTS: Totally, 426 patients with coronary artery disease were consecutively included. Serum FFA levels were significantly higher in the SCAC group than non-SCAC group (6.62 ± 2.17 vs. 5.13 ± 1.73 mmol/dl, p < 0.001). Logistic regression revealed that serum FFAs were independently associated with SCAC after adjusting for confounding factors in the whole cohort (OR 1.414, CI 1.237-1.617, p < 0.001), the non-DM group (OR 1.273, CI 1.087-1.492, p = 0.003) and the DM group (OR 1.939, CI 1.388-2.710, p < 0.001). ROC analysis revealed a serum FFA AUC of 0.695 (CI 0.641-0.750, p < 0.001) in the whole population. The diagnostic predictability was augmented (AUC = 0.775, CI 0.690-0.859, p < 0.001) in the DM group and decreased (AUC = 0.649, CI 0.580-0.718, p < 0.001) in the non-DM group. CONCLUSIONS: Serum FFA levels were independently associated with SCAC, and could have some predictive capacity for SCAC. The association was strongest in the DM group.


Assuntos
Doença da Artéria Coronariana/sangue , Diabetes Mellitus/sangue , Ácidos Graxos não Esterificados/sangue , Calcificação Vascular/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Diabetes Mellitus/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Ultrassonografia de Intervenção , Calcificação Vascular/diagnóstico por imagem
13.
J Sep Sci ; 44(14): 2785-2797, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33961332

RESUMO

Periplocin, as one of the components of cardiac glycosides in Cortex periplocae, exhibited cardiotonic effects. Orally ingesting periplocin in high doses or over prolonged periods would cause serious adverse reactions, especially cardiotoxicity, which limits the applications of periplocin in clinical therapy. It has been reported that Panax notoginseng saponins could be used in compatibility with periplocin to reduce the cardiotoxicity of periplocin. To clarify the mechanisms of periplocin-induced cardiotoxicity and compatibility-pairing in reducing cardiotoxicity, the gas chromatography-mass spectrometry method was used to detect and analyze the metabolic profiles of rat plasma and urine samples after oral administration of periplocin, Panax notoginseng saponins, and the different compatibility ratios of periplocin and Panax notoginseng saponins. The multivariate statistical analysis method was used to screen and identify the biomarkers. A total of 49 potential biomarkers (28 in plasma and 21 in urine) associated with periplocin-induced cardiotoxicity were identified. Seven pathways were found through metabolomic pathway analysis. Moreover, the levels of 42 biomarkers (22 in plasma and 20 in urine) were close to normal after compatibility pairing. By analyzing the relative metabolic pathways, Panax notoginseng saponins could effectively reduce the cardiotoxicity of periplocin by affecting the tricarboxylic acid cycle, energy metabolism, and arachidonic acid metabolism.


Assuntos
Cardiotoxicidade/tratamento farmacológico , Metabolômica/métodos , Panax notoginseng/química , Saponinas/farmacologia , Animais , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Cromatografia Gasosa-Espectrometria de Massas/métodos , Extratos Vegetais/farmacologia , Ratos , Saponinas/toxicidade , Espectrometria de Massas em Tandem/métodos
14.
Pattern Recognit ; 119: 108055, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34103766

RESUMO

Novel coronavirus 2019 (COVID-19) has spread rapidly around the world and is threatening the health and lives of people worldwide. Early detection of COVID-19 positive patients and timely isolation of the patients are essential to prevent its spread. Chest X-ray images of COVID-19 patients often show the characteristics of multifocality, bilateral hairy glass turbidity, patchy network turbidity, etc. It is crucial to design a method to automatically identify COVID-19 from chest X-ray images to help diagnosis and prognosis. Existing studies for the classification of COVID-19 rarely consider the role of attention mechanisms on the classification of chest X-ray images and fail to capture the cross-channel and cross-spatial interrelationships in multiple scopes. This paper proposes a multi-kernel-size spatial-channel attention method to detect COVID-19 from chest X-ray images. Our proposed method consists of three stages. The first stage is feature extraction. The second stage contains two parallel multi-kernel-size attention modules: multi-kernel-size spatial attention and multi-kernel-size channel attention. The two modules capture the cross-channel and cross-spatial interrelationships in multiple scopes using multiple 1D and 2D convolutional kernels of different sizes to obtain channel and spatial attention feature maps. The third stage is the classification module. We integrate the chest X-ray images from three public datasets: COVID-19 Chest X-ray Dataset Initiative, ActualMed COVID-19 Chest X-ray Dataset Initiative, and COVID-19 radiography database for evaluation. Experimental results demonstrate that the proposed method improves the performance of COVID-19 detection and achieves an accuracy of 98.2%.

15.
Langmuir ; 36(35): 10361-10370, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32787008

RESUMO

Biopolymers such as polysaccharides and proteins have been widely used for the chiral separation of various components due to the intrinsic chirality of the polymers. Amyloid-like short peptides can also self-assemble into diverse chiral supramolecular nanostructures or polymers with precisely tailored architectures driving by noncovalent interactions. However, the use of such supramolecular nanostructures for the resolution and separation of chiral components remains largely unexplored. Here, we report that the self-assembled peptide supramolecular nanostructures can be used for the highly efficient chiral separation of various enantiomers. By rationally designing the constituent amino acid sequence of the peptides and the self-assembling environment, we can fabricate supramolecular polymers with distinct surface charges and architectures, including nanohelices, nanoribbons, nanosheets, nanofibrils, and nanospheres. The various supramolecular nanostructures were then used to resolve the racemic mixtures of α-methylbenzylamine, 2-phenylpropionic acid, and 1-phenylethanol. The results indicated that the self-assembled peptide polymers showed excellent enantioselective separation efficiency for different chiral molecules. The enantioselective separation efficiency of the peptide nanostructures can be tailored by changing their surface charges, morphology, and the constituent amino acid sequences of the peptides.

16.
J Interv Cardiol ; 2020: 4094121, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32508540

RESUMO

While coronary revascularization strategies guided by instantaneous wave-free ratio (iFR) are, in general, noninferior to those guided by fractional flow reserve (FFR) with respect to the rate of major adverse cardiac events at one-year follow-up in patients with stable angina or an acute coronary syndrome, the overall accuracy of diagnosis with iFR in large patient cohorts is about 80% compared with the diagnosis with FFR. So far, it remains incompletely understood what factors contribute to the discordant diagnosis between iFR and FFR. In this study, a computational method was used to systemically investigate the respective effects of various cardiovascular factors on FFR and iFR. The results showed that deterioration in aortic valve disease (e.g., regurgitation or stenosis) led to a marked decrease in iFR and a mild increase in FFR given fixed severity of coronary artery stenosis and that increasing coronary microvascular resistance caused a considerable increase in both iFR and FFR, but the degree of increase in iFR was lower than that in FFR. These findings suggest that there is a high probability of discordant diagnosis between iFR and FFR in patients with severe aortic valve disease or coronary microcirculation dysfunction.


Assuntos
Síndrome Coronariana Aguda , Angina Estável , Valva Aórtica , Angiografia Coronária/métodos , Estenose Coronária , Vasos Coronários , Reserva Fracionada de Fluxo Miocárdico , Revascularização Miocárdica/métodos , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/etiologia , Angina Estável/diagnóstico , Angina Estável/etiologia , Valva Aórtica/patologia , Valva Aórtica/fisiopatologia , Simulação por Computador , Circulação Coronária , Estenose Coronária/diagnóstico , Estenose Coronária/fisiopatologia , Vasos Coronários/patologia , Vasos Coronários/fisiopatologia , Humanos , Seleção de Pacientes , Índice de Gravidade de Doença , Resistência Vascular
17.
Biol Pharm Bull ; 42(8): 1337-1344, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31167987

RESUMO

Diabetic cardiomyopathy (DCM) is a major complication of diabetes, and features myocardial fibrosis as its main pathological feature. Calcium sensing receptor (CaSR) is a G protein-coupled receptor, which involves in myocardial fibrosis by regulation of calcium homeostasis. Calhex231, the CaSR inhibitor, is not clear whether it regulates myocardial fibrosis in DCM. In the present study, type 1 diabetic (T1D) rats and primary neonatal rat cardiac fibroblasts were used to observe the role of Calhex231. In vivo experiments showed that in the T1D group, contractile dysfunction and the deposition of collagen I and III were obvious after 12 weeks. In vitro experiments, we found that high glucose (HG) could increase the expression of CaSR, α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) collagen I/III, matrix metalloproteinase-2 (MMP-2), MMP9, along with cardiac fibroblast migration and proliferation. We further demonstrated that CaSR activation increased intracellular Ca2+ concentration and upregulated the expression of Itch (atrophin-1 interacting protein 4), which resulted in increasing the ubiquitination levels of Smad7 and upregulating the expression of p-Smad2, p-Smad3. However, treatment with Calhex231 clearly inhibited the above-mentioned changes. Collectively these results suggest that Calhex231 could inhibit Itch-ubiquitin proteasome and TGF-ß1/Smads pathways, and then depress the proliferation of cardiac fibroblasts, along with the reduction deposition of collagen, alleviate glucose-induced myocardial fibrosis. Our findings indicate an important new mechanism for myocardial fibrosis, and suggest Calhex231 would be a new therapeutic agent for the treatment of DCM.


Assuntos
Benzamidas/farmacologia , Cicloexilaminas/farmacologia , Cardiomiopatias Diabéticas/patologia , Fibrose/tratamento farmacológico , Miocárdio/patologia , Receptores de Detecção de Cálcio/antagonistas & inibidores , Ubiquitina-Proteína Ligases/metabolismo , Animais , Cálcio/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Cardiomiopatias Diabéticas/induzido quimicamente , Cardiomiopatias Diabéticas/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibrose/metabolismo , Glucose/metabolismo , Coração , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Modelos Animais , Miocárdio/metabolismo , Cultura Primária de Células , Complexo de Endopeptidases do Proteassoma/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Proteína Smad7/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Ubiquitinas/metabolismo
18.
Cell Mol Biol Lett ; 24: 62, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798643

RESUMO

BACKGROUND: Myocardial ischaemia reperfusion injury (MIRI) is a difficult problem in clinical practice, and it may involve various microRNAs. This study investigated the role that endogenous microRNA-146a plays in myocardial ischaemia reperfusion and explored the possible target genes. METHODS: MIRI models were established in microRNA-146a deficient (KO) and wild type (WT) mice. MicroRNA-146a expression was evaluated in the myocardium of WT mice after reperfusion. The heart function, area of myocardium infarction and in situ apoptosis were compared between the KO and WT mice. Microarray was used to explore possible target genes of microRNA-146a, while qRT-PCR and dual luciferase reporter assays were used for verification. Western blotting was performed to detect the expression levels of the target gene and related signalling molecules. A rescue study was used for further testing. RESULTS: MicroRNA-146a was upregulated 1 h after reperfusion. MicroRNA-146a deficiency decreased heart function and increased myocardial infarction and apoptosis. Microarray detected 19 apoptosis genes upregulated in the KO mice compared with the WT mice. qRT-PCR and dual luciferase verified that Med1 was one target gene of microRNA-146a. TRAP220, encoded by Med1 in the KO mice, was upregulated, accompanied by an amplified ratio of Bax/Bcl2 and increased cleaved caspase-3. Inhibition of microRNA-146a in H9C2 cells caused increased TRAP220 expression and more apoptosis under the stimulus of hypoxia and re-oxygenation, while knockdown of the increased TRAP220 expression led to decreased cell apoptosis. CONCLUSIONS: MicroRNA-146a exerts a protective effect against MIRI, which might be partially mediated by the target gene Med1 and related to the apoptosis signalling pathway.


Assuntos
Subunidade 1 do Complexo Mediador/genética , MicroRNAs/genética , Infarto do Miocárdio/genética , Traumatismo por Reperfusão Miocárdica/genética , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Apoptose/genética , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Testes de Função Cardíaca , Masculino , Subunidade 1 do Complexo Mediador/antagonistas & inibidores , Subunidade 1 do Complexo Mediador/metabolismo , Camundongos , Camundongos Knockout , MicroRNAs/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Miócitos Cardíacos/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
19.
Sensors (Basel) ; 19(12)2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216632

RESUMO

To improve the controllability of an electro-hydraulic position servo control system while simultaneously enhancing the anti-jamming ability of a PID controller, a compound PID controller that combines the beetle antennae search algorithm with PID strategy was proposed, and used to drive the position servo control system of the electro-hydraulic servo system. A BAS-PID controller was designed, and the beetle antennae search algorithm was used to tune PID parameters so that the disturbance signal of the system was effectively restrained. Initially, the basic mathematical model of the electro-hydraulic position servo control system was established through theoretical analysis. The transfer function model was obtained by identifying system parameters. Then, the PID parameter-tuning problem was converted into a class of three-dimensional parameter optimization problem, and gains of PID controllers were adjusted using the beetle antennae search algorithm. Finally, by comparing the effectiveness of different algorithms, simulation and experimental results revealed that the BAS-PID controller can greatly enhance the performance of the electro-hydraulic position servo control system and inhibit external disturbances when different interference signals are used to test the system's robustness.

20.
Biochem Biophys Res Commun ; 503(3): 1372-1377, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30029876

RESUMO

Liver-X-receptors (LXRs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily. The two popular homologous receptor subtypes, LXRα and LXRß, exhibit differential expression patterns, thereby probably playing different roles in different contexts. This study aimed to evaluate the different roles of the two LXR subtypes and the mechanisms underlying their protection of cardiomyocytes against high-glucose stress. Silencing of LXRα, but not LXRß impaired normal LXR-mediated cardioprotective effects against high glucose-induced oxidative stress, apoptosis, and inflammation. Mechanistically, silencing of small ubiquitin-like modifier (SUMO)1 or SUMO2/3 did not affect LXR-mediated cardioprotective effects; however, these were impaired in response to nuclear receptor corepressor (NCoR) silencing. Together, these findings indicate that LXRα, but not LXRß, protects against high glucose-induced cardiomyocyte injury, probably via the NCoR-dependent transrepression of downstream target genes.


Assuntos
Glucose/farmacologia , Receptores X do Fígado/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Animais , Apoptose/efeitos dos fármacos , Benzoatos/farmacologia , Benzilaminas/farmacologia , Células Cultivadas , Inflamação/induzido quimicamente , Inflamação/metabolismo , Receptores X do Fígado/agonistas , Receptores X do Fígado/genética , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos
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