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1.
Biosci Rep ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33015714

RESUMO

Allergic Rhinitis (AR) is a non-infectious chronic inflammatory disease of nasal mucosa provoking Th17 response. Chlorogenic acid (CGA), one of the most abundant polyphenol compounds in various agricultural products, possess anti-viral, anti-inflammatory, and anti-bacterial properties. However, the effect of CGA on AR is unclear. Thus, our study explored the effect of CGA in modulating AR-related symptoms and immunoreaction especially Th17 response. AR mice were induced by ovalbumin (OVA) administration and further treated with CGA or dexamethasone. The frequencies of rubbing and sneezing of AR mice were recorded. Histopathological of nasal mucosa were conducted by hematoxylin-eosin staining and periodic acid-schiff staining. The serum and nasal mucosa levels of OVA-immunoglobulin (Ig)E, interferon (IFN)-γ, retinoic acid-associated nuclear orphan receptor (ROR)-γt, and interleukin (IL)-17A were measured by enzyme-linked immunosorbent assay, qRT-PCR, or western blot. The ratio of CD4+IL-17+Th17 cells to CD4+T cells in peripheral blood of AR mice was assessed by flow cytometer. CGA diminished the frequencies of rubbing and sneezing of AR mice in a concentration-dependent manner. CGA attenuated histopathological abnormalities and decreased goblet cell number in nasal mucosal of AR mice. CGA decreased the serum levels of OVA-IgE, ROR-γt, and IL-17A, while increasing the serum level of IFN-γ in AR mice. Meanwhile, CGA decreased the ratio of CD4+IL-17+Th17 cells to CD4+T cells in peripheral blood and the mRNA and protein levels of IL-17A and ROR-γt in AR mice. CGA ameliorated AR-related symptoms in mice by regulating Th17 cells, which could be a candidate for the treatment of AR.

2.
Sci Rep ; 10(1): 16840, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033325

RESUMO

Evolution of resistance by pests reduces the benefits of transgenic crops that produce insecticidal proteins from Bacillus thuringiensis (Bt). Here we analyzed resistance to Bt toxin Cry1Ac in a field-derived strain of pink bollworm (Pectinophora gossypiella), a global pest of cotton. We discovered that the r14 allele of the pink bollworm cadherin gene (PgCad1) has a 234-bp insertion in exon 12 encoding a mutant PgCad1 protein that lacks 36 amino acids in cadherin repeat 5 (CR5). A strain homozygous for this allele had 237-fold resistance to Cry1Ac, 1.8-fold cross-resistance to Cry2Ab, and developed from neonate to adult on Bt cotton producing Cry1Ac. Inheritance of resistance to Cry1Ac was recessive and tightly linked with r14. PgCad1 transcript abundance in midgut tissues did not differ between resistant and susceptible larvae. Toxicity of Cry1Ac to transformed insect cells was lower for cells expressing r14 than for cells expressing wild-type PgCad1. Wild-type PgCad1 was transported to the cell membrane, whereas PgCad1 produced by r14 was not. In larval midgut tissue, PgCad1 protein occurred primarily on the brush border membrane only in susceptible larvae. The results imply r14 mediates pink bollworm resistance to Cry1Ac by reduced translation, increased degradation, and/or mislocalization of cadherin.

3.
Mol Psychiatry ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051604

RESUMO

Numerous studies have used human pluripotent stem cell-derived cerebral organoids to elucidate the mystery of human brain development and model neurological diseases in vitro, but the potential for grafted organoid-based therapy in vivo remains unknown. Here, we optimized a culturing protocol capable of efficiently generating small human cerebral organoids. After transplantation into the mouse medial prefrontal cortex, the grafted human cerebral organoids survived and extended projections over 4.5 mm in length to basal brain regions within 1 month. The transplanted cerebral organoids generated human glutamatergic neurons that acquired electrophysiological maturity in the mouse brain. Importantly, the grafted human cerebral organoids functionally integrated into pre-existing neural circuits by forming bidirectional synaptic connections with the mouse host neurons. Furthermore, compared to control mice, the mice transplanted with cerebral organoids showed an increase in freezing time in response to auditory conditioned stimuli, suggesting the potentiation of the startle fear response. Our study showed that subcortical projections can be established by microtransplantation and may provide crucial insights into the therapeutic potential of human cerebral organoids for neurological diseases.

4.
Clin Appl Thromb Hemost ; 26: 1076029620964868, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33030047

RESUMO

To discuss the coagulation dysfunction in COVID-19 patients and to find new biomarkers to separate severe COVID-19 patients from mild ones. We use a retrospective analysis of 88 COVID-19 patients, and compare the coagulation function between severe and mild groups. We found the prothrombin time (PT), thrombin time (TT), D-dimer were significantly higher in the severe group (P < 0.05), and the highest area under the curve (AUC) is 0.91 for D-dimer, while the AUC of PT and TT were 0.80 and 0.61 respectively. We identified that D-dimer has a better value in predicting patients who are likely to develop into severe cases, with the sensitivity and specificity were 84.4% and 88.8%, respectively. D-dimer may be a good biomarker to separate the severe COVID-19 patients from the mild ones.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , Testes de Coagulação Sanguínea/métodos , Infecções por Coronavirus/complicações , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Pneumonia Viral/complicações , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/fisiopatologia , China , Estudos de Coortes , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Valor Preditivo dos Testes , Tempo de Protrombina , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença , Tempo de Trombina
5.
Nat Commun ; 11(1): 5232, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067466

RESUMO

Glycopeptide antibiotics (GPAs) are essential for the treatment of severe infectious diseases caused by Gram-positive bacteria. The emergence and spread of GPA resistance have propelled the search for more effective GPAs. Given their structural complexity, genetic intractability, and low titer, expansion of GPA chemical diversity using synthetic or medicinal chemistry remains challenging. Here we describe a synthetic biology platform, GPAHex (GPA Heterologous expression), which exploits the genes required for the specialized GPA building blocks, regulation, antibiotic transport, and resistance for the heterologous production of GPAs. Application of the GPAHex platform results in: (1) a 19-fold increase of corbomycin titer compared to the parental strain, (2) the discovery of a teicoplanin-class GPA from an Amycolatopsis isolate, and (3) the overproduction and characterization of a cryptic nonapeptide GPA. GPAHex provides a platform for GPA production and mining of uncharacterized GPAs and provides a blueprint for chassis design for other natural product classes.

6.
Cell Death Dis ; 11(9): 818, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999280

RESUMO

As a deubiqutinase Otub1 stabilizes and promotes the oncogenic activity of the transcription factor c-Maf in multiple myeloma (MM), a malignancy of plasma cells. In the screen for bioactive inhibitors of the Otub1/c-Maf axis for MM treatment, nanchangmycin (Nam), a polyketide antibiotic, was identified to suppress c-Maf activity in the presence of Otub1. By suppressing Otub1, Nam induces c-Maf polyubiquitination and subsequent degradation in proteasomes but does not alter its mRNA level. Consistently, Nam downregulates the expression of CCND2, ARK5, and ITGB7, the downstream genes regulated by c-Maf, and promotes MM cell apoptosis as evidenced by PARP and Caspase-3 cleavage, as well as Annexin V staining. In line with the hypothesis, overexpression of Otub1 partly rescues Nam-induced MM cell apoptosis, and interestingly, when Otub1 is knocked down, Nam-decreased MM cell survival is also partly ablated, suggesting Otub1 is essential for Nam anti-MM activity. Nam also displays potent anti-MM activity synergistically with Doxorubicin or lenalidomide. In the in vivo assays, Nam almost completely suppresses the growth of MM xenografts in nude mice at low dosages but it shows no toxicity. Given its safety and efficacy, Nam has a potential for MM treatment by targeting the Otub1/c-Maf axis.

7.
J Colloid Interface Sci ; 583: 299-309, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-33007586

RESUMO

"Two-for-one" strategy is an effective method to construct two kinds of materials from a single precursor owing to the simplicity of fabricating procedure and reduction of manufacturing cost. However, such a strategy has seldom been utilized to produce both battery-type and capacitive electrodes of a hybrid supercapacitor (HSC) device. Here, we adopt the "two-for-one" strategy to fabricate three-dimensional (3D) porous iron-doped (Fe-doped) Co3O4 and nitrogen-doped (N-doped) carbon via a single bimetallic metal-organic framework, FeCo-ZIF-67. Fe-doped amounts and carbonization temperature are used to adjust their individual electrochemical behaviors. The optimal 3D porous Fe-doped Co3O4 and N-doped carbon possess a high capacitance of 767.9 and 277C g-1 at 1 A g-1, respectively. Charge storage mechanism of Fe-doped Co3O4 is further investigated via analysis of capacitive and diffusion-controlled contribution. A Fe-doped Co3O4//N-doped carbon HSC device achieves desirable specific energy (37 Wh kg-1) and power (750 Wkg-1), and satisfied cycling stability (90% retention after 4000 cycles). A light-emitting diode (LED) is successfully light by the HSC device, suggesting its potential application in the field of green energy conversion and storage devices.

8.
Sensors (Basel) ; 20(19)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977508

RESUMO

Point set is a major type of 3D structure representation format characterized by its data availability and compactness. Most former deep learning-based point set models pay equal attention to different point set regions and channels, thus having limited ability in focusing on small regions and specific channels that are important for characterizing the object of interest. In this paper, we introduce a novel model named Attention-based Point Network (AttPNet). It uses attention mechanism for both global feature masking and channel weighting to focus on characteristic regions and channels. There are two branches in our model. The first branch calculates an attention mask for every point. The second branch uses convolution layers to abstract global features from point sets, where channel attention block is adapted to focus on important channels. Evaluations on the ModelNet40 benchmark dataset show that our model outperforms the existing best model in classification tasks by 0.7% without voting. In addition, experiments on augmented data demonstrate that our model is robust to rotational perturbations and missing points. We also design a Electron Cryo-Tomography (ECT) point cloud dataset and further demonstrate our model's ability in dealing with fine-grained structures on the ECT dataset.

9.
Sci Rep ; 10(1): 15809, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978450

RESUMO

Emerging infectious pathogens that threaten blood transfusions are known to be present in blood samples from healthy/qualified donors. The objective of this study was to investigate the microbiome of blood from healthy donors from the Luzhou area in southwestern China. Potential pathogens and cytomegalovirus (CMV) infection in the donor blood were identified. Total plasma nucleic acids were extracted from one pool of 5734 samples and were constructed for metagenomics analysis using Illumina sequencing. The microbiome and potential emerging/re-emerging pathogens were identified using bioinformatics analysis. Moreover, CMV antigen was measured via an enzyme-linked immunosorbent assay, and the CMV DNA level was assessed by quantitative RT-PCR. A total of 132 bacterial reads, 65 viral reads and 165 parasitic reads were obtained. The most frequent bacterium was Escherichia coli (95/132, 72%) with 95 reads in 132 bacterial reads, and the most prevalent parasite was Toxoplasma gondii (131/165, 79%). Among the viruses, cytomegalovirus (44/65, 68%) accounted for the highest frequency, followed by Hepatitis E Virus (10/65, 15%). Moreover, the positive rate of CMV-IgG was 46.25% (2652/5734), and the positive rate of CMV-IgM was 5.82% (334/5734). The positive rate of dual positive (IgG+ and IgM+) CMV was 0.07% (4/5734). Twenty-one (0.37%) specimens from 5734 donated blood samples were positive for CMV DNA. The CMV DNA levels ranged from 7.56 × 102 to 3.58 × 103 copies/mL. The current study elucidated the microbiome structure in blood from healthy/qualified donors in the Luzhou area and identified emerging/re-emerging pathogens. This preliminary study contributes to information regarding blood transfusion safety in China.

10.
Behav Brain Res ; : 112898, 2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32905810

RESUMO

The burden of depression is enormous, and numerous studies have found that major depressive disorder (MDD) induces cardiovascular disorders (CVD) and functional dyspepsia (FD). Excitingly, meranzin hydrate (MH), an absorbed bioactive compound of Aurantii Fructus Immaturus, reverses psychosocial stress-induced mood disorders, gastrointestinal dysfunction and cardiac disease. Pharmacological methods have repeatedly failed in antidepressant development over the past few decades, but repairing aberrant neural circuits might be a reasonable strategy. This article aimed to explore antidepressant-like effects and potential mechanisms of MH in a rat model of unpredictable chronic mild stress (UCMS). Utilizing blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), we sought to find reliable neurocircuits or a dominant brain region revealing the multiple effects of MH. The results show that compared with UCMS rats, MH (10 mg/kg/day for 1 week i.g.)-treated rats exhibited decreased depression-like behaviour; increased expression of brain-derived neurotrophic factor (BDNF) in the hippocampal dentate gyrus; and normalized levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and acylated ghrelin (AG). Additionally, the UCMS-induced rise in BOLD activation in the reward system was attenuated after MH treatment. A literature search shown that nucleus accumbens (NAc) and hypothalamus of the reward system might reveal multiple effects of MH on MDD-FD-CVD comorbidity. Further research will focus on the role of these two brain regions in treating depression associated with comorbidities.

11.
Science ; 369(6508)2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32883833

RESUMO

Sleep and wakefulness are homeostatically regulated by a variety of factors, including adenosine. However, how neural activity underlying the sleep-wake cycle controls adenosine release in the brain remains unclear. Using a newly developed genetically encoded adenosine sensor, we found an activity-dependent rapid increase in the concentration of extracellular adenosine in mouse basal forebrain (BF), a critical region controlling sleep and wakefulness. Although the activity of both BF cholinergic and glutamatergic neurons correlated with changes in the concentration of adenosine, optogenetic activation of these neurons at physiological firing frequencies showed that glutamatergic neurons contributed much more to the adenosine increase. Mice with selective ablation of BF glutamatergic neurons exhibited a reduced adenosine increase and impaired sleep homeostasis regulation. Thus, cell type-specific neural activity in the BF dynamically controls sleep homeostasis.

12.
Appl Opt ; 59(24): 7434-7441, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32902511

RESUMO

A light field microscope can realize three-dimensional measurement through only one exposure by the addition of a critical optical component called a microlens array (MLA). MLA errors will introduce aberrations in the captured image and then affect measurement results. This paper proposes a light field measuring system with aberration correction based on imaging analysis. The effect of MLA errors is investigated and quantitatively analyzed through a series of simulation studies. Aberration correction is realized based on computational imaging, in which an image segmentation and fusion distortion model is employed to correct the distortion, while a gradient-based linear recognition algorithm is used to address MLA rotation errors. Experimental results show that the developed light field measuring system can achieve improved measurement accuracy by correcting aberrations with the proposed algorithms.

13.
J Hazard Mater ; 400: 123158, 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-32947736

RESUMO

Ambient particulate matter (PM2.5)-induced metabolic syndromes is a critical contributor to the pathological processes of neurological diseases, but the underlying molecular mechanisms remain poorly understood. The rhomboid 5 homolog 2 (Rhbdf2), an essential regulator in the production of TNF-α, has recently been confirmed to exhibit a key role in regulating inflammation-associated diseases. Thus, we examined whether Rhbdf2 contributes to hypothalamic inflammation via NF-κB associated inflammation activation in long-term PM2.5-exposed mice. Specifically, proopiomelanocortin-specific Rhbdf2 deficiency (Rhbdf2Pomc) and corresponding littermates control mice were used for the current study. After 24 weeks of PM2.5 inhalation, systemic-metabolism disorder was confirmed in WT mice in terms of impaired glucose tolerance, increased insulin resistance, and high blood pressure. Markedly, PM2.5-treated Rhbdf2Pomc mice displayed a significantly opposite trend in these parameters compared with those of the controls group. We next confirmed hypothalamic injury accompanied by abnormal POMC neurons loss, as indicated by increased inflammatory cytokines, chemokines, and oxidative-stress levels and decreased antioxidant activity. These results were further supported by blood routine examination. In summary, our findings suggest that Rhbdf2 plays an important role in exacerbating PM2.5-stimulated POMC neurons loss associated hypothalamic injury, thus providing a possible target for blocking pathological development of air pollution-associated diseases.

15.
BMC Bioinformatics ; 21(1): 399, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907544

RESUMO

BACKGROUND: Cryo-electron tomography is an important and powerful technique to explore the structure, abundance, and location of ultrastructure in a near-native state. It contains detailed information of all macromolecular complexes in a sample cell. However, due to the compact and crowded status, the missing edge effect, and low signal to noise ratio (SNR), it is extremely challenging to recover such information with existing image processing methods. Cryo-electron tomogram simulation is an effective solution to test and optimize the performance of the above image processing methods. The simulated images could be regarded as the labeled data which covers a wide range of macromolecular complexes and ultrastructure. To approximate the crowded cellular environment, it is very important to pack these heterogeneous structures as tightly as possible. Besides, simulating non-deformable and deformable components under a unified framework also need to be achieved. RESULT: In this paper, we proposed a unified framework for simulating crowded cryo-electron tomogram images including non-deformable macromolecular complexes and deformable ultrastructures. A macromolecule was approximated using multiple balls with fixed relative positions to reduce the vacuum volume. A ultrastructure, such as membrane and filament, was approximated using multiple balls with flexible relative positions so that this structure could deform under force field. In the experiment, 400 macromolecules of 20 representative types were packed into simulated cytoplasm by our framework, and numerical verification proved that our method has a smaller volume and higher compression ratio than the baseline single-ball model. We also packed filaments, membranes and macromolecules together, to obtain a simulated cryo-electron tomogram image with deformable structures. The simulated results are closer to the real Cryo-ET, making the analysis more difficult. The DOG particle picking method and the image segmentation method are tested on our simulation data, and the experimental results show that these methods still have much room for improvement. CONCLUSION: The proposed multi-ball model can achieve more crowded packaging results and contains richer elements with different properties to obtain more realistic cryo-electron tomogram simulation. This enables users to simulate cryo-electron tomogram images with non-deformable macromolecular complexes and deformable ultrastructures under a unified framework. To illustrate the advantages of our framework in improving the compression ratio, we calculated the volume of simulated macromolecular under our multi-ball method and traditional single-ball method. We also performed the packing experiment of filaments and membranes to demonstrate the simulation ability of deformable structures. Our method can be used to do a benchmark by generating large labeled cryo-ET dataset and evaluating existing image processing methods. Since the content of the simulated cryo-ET is more complex and crowded compared with previous ones, it will pose a greater challenge to existing image processing methods.


Assuntos
Citoplasma/ultraestrutura , Tomografia com Microscopia Eletrônica/métodos , Simulação de Dinâmica Molecular , Algoritmos , Análise por Conglomerados , Microscopia Crioeletrônica , Citoplasma/metabolismo , Processamento de Imagem Assistida por Computador , Substâncias Macromoleculares/química , Substâncias Macromoleculares/metabolismo , Razão Sinal-Ruído
16.
Nat Methods ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32989318

RESUMO

The ability to directly measure acetylcholine (ACh) release is an essential step toward understanding its physiological function. Here we optimized the GRABACh (GPCR-activation-based ACh) sensor to achieve substantially improved sensitivity in ACh detection, as well as reduced downstream coupling to intracellular pathways. The improved version of the ACh sensor retains the subsecond response kinetics, physiologically relevant affinity and precise molecular specificity for ACh of its predecessor. Using this sensor, we revealed compartmental ACh signals in the olfactory center of transgenic flies in response to external stimuli including odor and body shock. Using fiber photometry recording and two-photon imaging, our ACh sensor also enabled sensitive detection of single-trial ACh dynamics in multiple brain regions in mice performing a variety of behaviors.

17.
Ther Drug Monit ; 42(5): 716-723, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32941397

RESUMO

BACKGROUND: Polymyxin B is used as the last treatment resort for multidrug-resistant gram-negative bacterial infections. This study aimed to develop and validate a simple and robust liquid chromatography with tandem mass spectrometry analytical method for therapeutic drug monitoring of plasma and cerebrospinal fluid (CSF) polymyxin B1 and B2. METHODS: Plasma and CSF polymyxin B1 and B2 were chromatographically separated on a Thermo Hypersil GOLD aQ C18 column and detected using electrospray ionization mode coupled with multiple reaction monitoring. Blood and CSF samples for pharmacokinetic analysis were collected from 15 polymyxin B-treated patients. RESULTS: The calibration curve showed acceptable linearity over 0.2-10 mcg/mL for polymyxin B1 and 0.05-2.5 mcg/mL for B2 in the plasma and CSF, respectively. After validation, according to the Food and Drug Administration (FDA) method validation guideline, this method was applied for polymyxin B1 and B2 quantification in over 100 samples in a clinical study. CONCLUSIONS: A simple and robust method to measure polymyxin B1 and B2 in human CSF was first exploited and validated with good sensitivity and specificity, and successfully applied in polymyxin B pharmacokinetic analysis and therapeutic monitoring in Chinese patients.

18.
mBio ; 11(5)2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32900806

RESUMO

Clinical development of antibiotics with novel mechanisms of action to kill pathogenic bacteria is challenging, in part, due to the inevitable emergence of resistance. A phenomenon of potential clinical importance that is broadly overlooked in preclinical development is heteroresistance, an often-unstable phenotype in which subpopulations of bacterial cells show decreased antibiotic susceptibility relative to the dominant population. Here, we describe a new globomycin analog, G0790, with potent activity against the Escherichia coli type II signal peptidase LspA and uncover two novel resistance mechanisms to G0790 in the clinical uropathogenic E. coli strain CFT073. Building on the previous finding that complete deletion of Lpp, the major Gram-negative outer membrane lipoprotein, leads to globomycin resistance, we also find that an unexpectedly modest decrease in Lpp levels mediated by insertion-based disruption of regulatory elements is sufficient to confer G0790 resistance and increase sensitivity to serum killing. In addition, we describe a heteroresistance phenotype mediated by genomic amplifications of lspA that result in increased LspA levels sufficient to overcome inhibition by G0790 in culture. These genomic amplifications are highly unstable and are lost after as few as two subcultures in the absence of G0790, which places amplification-containing resistant strains at high risk of being misclassified as susceptible by routine antimicrobial susceptibility testing. In summary, our study uncovers two vastly different mechanisms of resistance to LspA inhibitors in E. coli and emphasizes the importance of considering the potential impact of unstable and heterogenous phenotypes when developing antibiotics for clinical use.IMPORTANCE Despite increasing evidence suggesting that antibiotic heteroresistance can lead to treatment failure, the significance of this phenomena in the clinic is not well understood, because many clinical antibiotic susceptibility testing approaches lack the resolution needed to reliably classify heteroresistant strains. Here we present G0790, a new globomycin analog and potent inhibitor of the Escherichia coli type II signal peptidase LspA. We demonstrate that in addition to previously known mechanisms of resistance to LspA inhibitors, unstable genomic amplifications containing lspA can lead to modest yet biologically significant increases in LspA protein levels that confer a heteroresistance phenotype.

19.
Glob Heart ; 15(1): 59, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32923352

RESUMO

Aims: To examine whether electrocardiography (ECG) could provide additional values to the traditional risk factors for cardiovascular disease (CVD) risk prediction among different cardiovascular risk subgroups. Methods: A total of 7,872 community residents aged ≥40 years were followed up for a median of 4.5 years. A 12-lead resting ECG was examined for participants at baseline. CVD events including myocardial infarction, stroke and cardiovascular mortality were collected. Cox proportional hazards models were used and models of traditional risk factors with and without ECG were compared. Results: At baseline, 2,470 participants (31.3%) had ECG abnormalities. During follow-up, 464 participants developed CVD events. ECG abnormalities were associated with an increased risk of CVD after adjustment for the traditional risk factors in participants with a 10-year atherosclerotic CVD (ASCVD) risk ≥10% (hazard ratio, HR: 1.45; 95% confidence interval, CI: 1.11, 1.91). Adding ECG abnormalities to the traditional CVD risk factors improved reclassification for those who did not experience events [net reclassification index: 8.0% (95% CI: 2%, 19.5%)], discrimination (integrated discrimination improvement: 0.7% (95% CI: 0.1%, 1.9%), and calibration (goodness of fit P value from 0.600 to 0.873) in participants with a 10-year ASCVD risk ≥10%. However, no significant association and improvement were found in participants with a 10-year ASCVD risk <10%. Conclusions: ECG screening might provide a marginal improvement in CVD risk prediction in adults at high risk. However, ECG should not be recommended in adults at low risk.

20.
J Am Heart Assoc ; 9(18): e017970, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32865120

RESUMO

Background Hypertensive myocardial fibrosis (MF) is characterized by excessive deposition of extracellular matrix and cardiac fibroblast proliferation, which can lead to heart failure, malignant arrhythmia, and sudden death. In recent years, with the deepening of research, microRNAs have been found to have an important role in blood pressure control and maintaining normal ventricular structure and function. Methods and Results In this study, we first documented the downregulation of microRNA-26a (miR-26a) in the plasma and myocardium of spontaneously hypertensive rats; more importantly, miR-26a-deficient mice showed MF, whereas overexpression of miR-26a significantly prevented elevated blood pressure and inhibited MF in vivo and angiotensin II-induced fibrogenesis in cardiac fibroblasts by directly targeting connective tissue growth factor and Smad4. miR-26a inhibited cardiac fibroblast proliferation by the enhancer of zeste homolog 2/p21 pathway. Conclusions Our study identified a novel role for miR-26a in blood pressure control and hypertensive MF and provides a possible treatment strategy for miR-26a to alleviate and reverse hypertensive MF.

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