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1.
Cerebrovasc Dis ; : 1-9, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31514187

RESUMO

Default mode network (DMN) is an important functional brain network that supports aspects of cognition. Stroke has been reported to be associated with functional connectivity (FC) impairments within DMN. However, whether FC within DMN changes in transient ischemic attack (TIA), an important risk factor for stroke, remains unclear. Forty-eight TIA patients and 41 age- and sex-matched healthy controls (HCs) were recruited in this study. Using resting-state functional magnetic resonance imaging seed-based FC methods, we examined FC alterations within DMN in TIA patients, tested its associations with clinical information, and further explored the ability of FC abnormalities to predict follow-up ischemic attacks. We found significantly decreased FC of left middle temporal gyrus/angular gyrus both with medial prefrontal cortex (mPFC) and posterior cingulate cortex/precuneus (PCC/Pcu) and significantly decreased FC among each pair of mPFC, left PCC, and right Pcu in patients with TIA as compared with HCs. Moreover, the connectivity between mPFC and left PCC could predict future ischemic attacks of the patients. Collectively, these findings may provide insights into further understanding of the underlying pathological mechanism in TIA, and aberrant FC between the hubs within DMN may provide a reference for the imaging diagnosis and early intervention of TIA.

2.
Acta Pharmacol Sin ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31515530

RESUMO

Abnormal growth of the intimal layer of blood vessels (neointima formation) contributes to the progression of atherosclerosis and in-stent restenosis. Recent evidence shows that the 18-kDa translocator protein (TSPO), a mitochondrial membrane protein, is involved in diverse cardiovascular diseases. In this study we investigated the role of endogenous TSPO in neointima formation after angioplasty in vitro and in vivo. We established a vascular injury model in vitro by using platelet-derived growth factor-BB (PDGF-BB) to stimulate rat thoracic aortic smooth muscle cells (A10 cells). We found that treatment with PDGF-BB (1-20 ng/mL) dose-dependently increased TSPO expression in A10 cells, which was blocked in the presence of PKC inhibitor or MAPK inhibitor. Overexpression of TSPO significantly promoted the proliferation and migration in A10 cells, whereas downregulation of TSPO expression by siRNA or treatment with TSPO ligands PK11195 or Ro5-4864 (104 nM) produced the opposite effects. Furthermore, we found that PK11195 (10-104 nM) dose-dependently activated AMPK in A10 cells. PK11195-induced inhibition on the proliferation and migration of PDGF-BB-treated A10 cells were abolished by compound C (an AMPK-specific inhibitor, 103 nM). In rats with balloon-injured carotid arteries, TSPO expression was markedly upregulated in the carotid arteries. Administration of PK11195 (3 mg/kg every 3 days, ip), starting from the initial balloon injury and lasting for 2 weeks, greatly attenuated carotid neointima formation by suppressing balloon injury-induced phenotype switching of VSMCs (increased α-SMA expression). These results suggest that TSPO is a vascular injury-response molecule that promotes VSMC proliferation and migration and is responsible for the neointima formation after vascular injury, which provides a novel therapeutic target for various cardiovascular diseases including atherosclerosis and restenosis.

3.
Appl Opt ; 58(23): 6325-6328, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503777

RESUMO

In this paper, we realize the generation of propagation-invariant vector beams with square array by use of a 2D binary phase mask and pentagonal prism in a typical Mach-Zehnder optical system. The binary phase mask set in the optical system is perpendicular to the optical axis, and its periodic orientation is 45° relative to the horizontal and vertical directions. One polarizer was used to produce the linearly polarized beam with the angle of 45° relative to the horizontal and vertical directions. One mirror in the Mach-Zehnder optical system was replaced by a pentagonal prism, as the light will be reflected twice inside the pentagonal prism. The intensity distribution of the two branches with the mirror and pentagonal prism have mirror symmetry, and the output optical field of the two branches has an orthogonal polarization state. By adjusting the position of the phase plate accordingly, the total optical field of the two branches can form a vector beam with a square array. The experimental results coincide with the simulation results very well and demonstrate the feasibility of this method.

4.
JAMA Surg ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31509166
5.
Artigo em Inglês | MEDLINE | ID: mdl-31501939

RESUMO

While previous work has demonstrated that antimonate (Sb(V)) can be bio-reduced with methane as the sole electron donor, the microorganisms responsible for Sb(V) reduction remain largely uncharacterized. Inspired by the recently reported Sb(V) reductase belonging to the dimethyl sulfoxide reductase (DMSOR) family, this study was undertaken to use metagenomics and metatranscriptomics to unravel whether any DMSOR family genes in the bioreactor had the potential for Sb(V) reduction. A search through metagenomic-assembled genomes recovered from the microbial community found that some DMSOR family genes, designated sbrA (Sb(V) reductase gene), were highly transcribed in four phylogenetically disparate assemblies. The putative catalytic subunits were found to be representatives of two distinct phylogenetic clades of reductases that were most closely related to periplasmic nitrate reductases and respiratory arsenate reductases, respectively. Putative operons containing sbrA possessed many other components, including genes encoding c-type cytochromes, response regulators, and ferredoxins, which together implement Sb(V) reduction. This predicted ability was confirmed by incubating the enrichment culture with 13C-labeled CH4 and Sb(V) in serum bottles, where Sb(V) was reduced coincident with the production of 13C-labeled CO2. Overall, these results increase our understanding of how Sb(V) can be bio-reduced in environments.

6.
IUBMB Life ; 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31444899

RESUMO

Atherosclerosis is a common and deadly cardiovascular disease with extremely high prevalence. Areas of the vasculature exposed to oscillatory shear stress (OSS) or disturbed blood flow are particularly prone to the development of atherosclerotic lesions. In part, various mechanosensitive receptors on the surface of endothelial cells play a role in regulating the ability of the vasculature to cope with variations in blood flow patterns. However, the exact mechanisms behind flow-mediated endothelial responses remain poorly understood. Along with the development of highly specific receptor agonists, the class of G coupled-protein receptors has been receiving increasing attention as potential therapeutic targets. G coupled-protein receptor 81 (GPR81), also known as hydroxycarboxylic acid receptor 1 (HCA1 ), is activated by lactate, its endogenous ligand. In the present study, we show for the first time that expression of GPR81 is significantly downregulated in response to OSS in endothelial cells and that activation of GPR81 using physiologically relevant doses of lactate can rescue OSS-induced reduced GPR81 expression. Importantly, our findings demonstrate that activation of GPR81 can exert valuable atheroprotective effects in endothelial cells exposed to OSS by reducing oxidative stress and significantly downregulating the expression of inflammatory cytokines including interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, and high mobility group box 1 (HMGB1). We also show that activation of GPR81 can potentially prevent the attachment of monocytes to the endothelium by suppressing OSS-induced secretion of vascular cellular adhesion molecule (VCAM)-1 and endothelial-selectin (E-selectin). Finally, we show that activation of GPR81 can rescue OSS-induced reduced expression of the key atheroprotective transcription factor Kruppel-like factor 2 (KLF2), which is mediated through the extracellular-regulated kinase 5 (ERK5) pathway. These findings demonstrate a potential protective role of GPR81 against atherogenesis and that targeted activation of GPR81 may inhibit endothelial inflammation and dysfunction induced by OSS.

8.
J Immunotoxicol ; 16(1): 155-163, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31403359

RESUMO

Exposure to the widely-used phthalate plasticizer di-(2-ethylhexyl)-phthalate (DEHP) has been shown to be closely related to an increased prevalence of allergic diseases in infants and juveniles. Earlier work in our laboratory found that DEHP-related anaphylactic responses could be ascribed to T-follicular helper (Tfh) cell hyperfunction directly. The Tfh cell, a newly identified CD4+ TH cell subset, until recently has been considered as a key player in humoral immunity. Tfh cells can respond to stimulation through various receptors. Signaling lymphocytic activation molecule family member-1 (SLAMF1, CD150) is a surface co-stimulatory receptor that can bind to an intracytoplasmic adaptor signaling lymphocytic activation molecule-associated protein (SAP) to initiate downstream signaling cascades, regulating some events of immune response. The present study explored the role of SLAMF1 in Tfh cell differentiation and cytokine secretion under the condition of DEHP exposure. Using a weanling mice model of DEHP gavage with ovalbumin (OVA) sensitization, it was found that DEHP acted as an immunoadjuvant to elevate SLAMF1 and SAP expression in host Tfh cells. Ex vivo studies of effects from DEHP exposure on Tfh cells from OVA-sensitized hosts showed that DEHP acted in an adjuvant-like manner to promote the expression of adaptor protein SAP, transcription factors Bcl-6 and c-MAF, and cytokines interleukin (IL)-21 and IL-4 in Tfh cells. Transfection of these Tfh cells with Slamf1 small interfering RNA prior to exposure to the DEHP attenuated the over-expression of these molecules that was caused by the DEHP. In conclusion, this study demonstrated that DEHP, via a SLAMF1-mediated pathway, can impact on Tfh cell differentiation and their ability to form select cytokines.

9.
Microbiologyopen ; : e910, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31452334

RESUMO

Fibronectin-binding protein A (FnBPA) is a key adhesin of Staphylococcus aureus, and the protein binding to fibrinogen and elastin is mediated by its N-terminal A domain. Thus, FnBPA-A has been considered a potential vaccine candidate, but the relevant epitopes are not fully understood. Here, purified rabbit anti-FnBPA-A antibodies were produced and used to screen for peptides corresponding to or mimicking the epitope of native FnBPA-A protein by using a phage random 12-mer peptide library. After four rounds of panning, 25 randomly selected phage clones were detected by phage-ELISA and competition-inhibition ELISA. Then, eight anti-rFnBPA-A antibody-binding phage clones were selected for sequencing, and six different 12-mer peptides were displayed by these phages. Although these displayed peptides shared no more than three consecutive amino acid residues identical to the sequence of FnBPA-A, they could be recognized by the FnBPA-A-specific antibodies in vitro and could induce specific antibodies against FnBPA-A in vivo, suggesting that these displayed peptides were mimotopes of FnBPA-A. Finally, the protective efficiencies of these mimotopes were investigated by mouse vaccination and challenge experiments. Compared with that of control group mice, the relative percent survival of mice immunized with phage clones displaying a mimotope was 13.33% (C2 or C15), 0% (C8), 6.67% (C10), 26.67% (C19 or 1:2 mixture of C23 and C19), 53.33% (C23), 33.33% (1:1 mixture of C23 and C19), and 66.67% (2:1 mixture of C23 and C19). Overall, five peptides mimicking FnBPA-A protein epitopes were obtained, and a partially protective immunity against S. aureus infection could be stimulated by these mimotope peptides in mice.

10.
Asian J Psychiatr ; 44: 209-216, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31419738

RESUMO

Schizotypal personality (SP) traits have been found to be correlated with autistic traits, obsessive-compulsive traits, depressive symptoms and anxiety symptoms. However, the overall pattern of the relationship remains unclear. The purpose of this study was to investigate the network structure between SP traits and other subclinical features (symptoms or traits) and test the replicability of these relationships. A total of 2204 college students completed measurements for SP traits, autistic traits, obsessive-compulsive traits, depressive symptoms and anxiety symptoms, and a validated subsample of 814 completed the same questionnaires again three months later. Using network analysis, we constructed the network structure of subclinical features and then tested its replicability. We found that interpersonal features were the bridge node connecting SP traits and autistic traits (social skill: r = 0.50; attention switching: r = 0.14; communication: r = 0.12), while cognitive-perceptual (obsessing: r = 0.05; neutralizing: r = 0.06) and disorganization (obsessing: r = 0.11) features were the SP traits associated with obsessive-compulsive traits. In addition to interpersonal features (r = 0.10), disorganization (r = 0.12) and cognitive-perceptual (r = 0.05) features were also the overlap between depressive symptoms and SP traits. Anxiety symptoms only connected with interpersonal (r = 0.05) but not cognitive-perceptual features of SP traits. The network showed high predictability (43%) and interpersonal features of SP traits had the highest expected influence (1.67) among all nodes, which may be a potential target for intervention. High similarities were found on network structure (r = 0.86) and expected influence (r = 0.96), and no significant difference on global connectivity was found between these two networks (difference value = 0.45, p = 0.135), suggesting the replicability of the network structure.

11.
J Agric Food Chem ; 67(34): 9643-9651, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31390199

RESUMO

Licorice is a traditional Chinese medicine, which is often used as sweetener and cosmetic ingredients in food and pharmaceutical industries. Among them, glycyrrhetic acid is one of the most important agents. Studies have shown that glycyrrhetic acid exhibited antitumor activities as PPARγ agonist. However, the limited number of PPARγ glycyrrhetinic agonists and their high toxicity greatly limit the design based on the structure. Therefore, clarifying the binding mode between PPARγ and small molecules, we focused on the introduction of a natural active piperazine skeleton in the position of glycyrrhetinic acid C-3. According to the Combination Principle and the Structure-Based Drug Design, 19 glycyrrhetic acid derivatives were designed and synthesized as potential PPARγ agonists. Compounds 4c and 4q were screened as high-efficiency and low-toxicity lead compounds.

12.
Ying Yong Sheng Tai Xue Bao ; 30(7): 2137-2144, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31418215

RESUMO

Based on the biological characteristics of Cordyceps sinensis, combined with the spatial and temporal distribution characteristics of local agro-climatic resources and the investigation data of C. sinensis resources, we investigated the ecological climate suitability regionalization and the spatial distribution of C. sinensis in Shiqu County using mathematical statistics analysis, optimization method and GIS spatial analysis. We used altitude, mean annual temperature, mean annual precipitation, vegetation, and soil as the leading indicators and topographic gradient as the auxiliary indicators, as the main basis for the suitability zoning of C. sinensis resources. The results showed that C. sinensis grew in most of the townships in Shiqu County, with their distribution areas being fragmented and scattered, showing sporadic patches and blocks. They were mainly distributed in east and west parts of the county and in the Zhaqu River basin in the central part. The suitable distribution area for C. sinensis in Shiqu was 4000-4700 m above sea level, with mean annual temperature of -2.5-3 ℃ and mean annual precipitation of 550-850 mm. The growth environment was generally alpine mea-dow and subalpine meadow with good hydrophobicity and slope of 15°-50°. The suitable growth environment and meteorological conditions were beneficial to the growth and development of feeding plants and bat moths. The unsuitable area was in the high mountain area above the river wide valley area, pastoral area, wetland, or snowline.


Assuntos
Cordyceps , Sistemas de Informação Geográfica , China , Clima , Ecologia , Solo
13.
Schizophr Res ; 2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31387828

RESUMO

The present study aimed to explore the relationship between autistic and schizotypal traits in the non-clinical population. We first conducted a meta-analysis to quantify the correlation between self-reported autistic traits and the three dimensions of schizotypal traits (positive, negative and disorganization). The strongest correlation was found between autistic traits and negative schizotypal traits (r = 0.536, 95% CI [0.481, 0.586]), followed by the disorganization (r = 0.355, 95% CI [0.304, 0.404]) and positive (r = 0.256, 95% CI [0.208, 0.302]) dimensions. To visualize the partial correlations between dimensional behavioural traits, we constructed a network model based on a large sample of college students (N = 2469). Negative schizotypal traits were strongly correlated with autistic social/communicative deficits, whereas positive schizotypal traits were inversely correlated with autistic-like traits, lending support to the psychosis-autism diametrical model. Disentangling the overlapping and diametrical structure of autism and schizophrenia may help to elucidate the aetiology of these two neurodevelopmental disorders.

14.
Clin Epigenetics ; 11(1): 116, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31405379

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a genetic and epigenetic disease. There is growing evidence to suggest that environmental factors due to epigenetic changes can be involved in the OSCC pathogenesis. Although tumor suppressor genes (TSGs) are commonly inactivated by promoter hypermethylation in human cancers, the epigenetic changes and the mechanism of TSGs in human OSCC remain unclear. We therefore assessed the methylation status of the TSGs, which are associated with epigenetic silencing in human cancers, OSCC cell lines, primary tumors, and normal oral mucosa. RESULTS: We used 14 TSGs that were originally identified in colon cancer to investigate the aberrant hypermethylation of these genes associated with transcriptional silencing in 10 OSCC cell lines. We found three TSGs, TFPI2, SOX17, and GATA4, that are robustly hypermethylated and are associated with transcriptional silencing in OSCC cell lines. The re-expression of the three genes was induced by 5-aza-2'-deoxycytidine (5-aza-dC) in cells in which these genes were not expressed or had a lack of expression. In 33 cases of primary OSCC tumors, promoter hypermethylation was detected for the TFPI2, SOX17, and GATA4 genes at (32/33) 97%, (22/33) 67%, and (11/33) 33%, respectively. Eleven normal oral mucosa samples showed no promoter hypermethylation for all three genes, which suggests that this promoter hypermethylation is cancer-specific. Bisulfite sequencing analysis confirmed the cancer-specific methylation of the TFPI2, SOX17, and GATA4 promoters in the OSCC cell lines and tumors but not in the normal oral mucosa samples. More importantly, the methylation status of TFPI2, GATA4, and SOX17 was significantly associated with OSCC patients' overall survival through TCGA DNA methylation database. CONCLUSIONS: We identified that TFPI2, SOX17, and GATA4 are frequently hypermethylated in human OSCC cells in a cancer-specific manner and that the transcriptional expression of these genes is regulated by promoter hypermethylation in OSCC. Our results highlight the great potential used as a synergistic biomarker set to improve the prognosis and therapeutic treatment for patients with OSCC.

15.
Stem Cells ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31414513

RESUMO

The targeted delivery of therapeutic agents to secondary lymphoid organs (SLOs), where are the niches for immune initiation, provides an unprecedented opportunity for immune intolerance induction. The allo-immune rejection post vascularized composite allotransplantation (VCA) is mediated by T lymphocytes. Human adipose derived stem cells (hASCs) possess the superiority of convenient availability and potent immunoregulatory property, but its therapeutic results in the VCA is unambiguous thus far. Chemokine receptor 7 (CCR7) can specifically guide immune cells migrating into SLOs. There, genes of CCR7-GFP or GFP alone were introduced into hASCs by lentivirus. hASCs/CCR7 maintained the multi-differentiation and immunoregulatory abilities but gained the migration capacity elicited by SCL (CCR7 ligand) in vitro. Noteworthily, intravenously infused hASCs/CCR7 targetly relocated in the T cell aggression area in SLOs. In a rat VCA model, hASCs/GFP transfusion had rare effect on the allo-grafted vascularized composite. However, hASCs/CCR7 infusion potently prolonged the grafts' survival time. The ameliorated pathologic exhibition and the regulated inflammatory cytokines in the peripheral blood were also observed. The altered axis of Th1/Th2 and Tregs/Th17 in SLOs may underlie the down-regulated rejection response. Moreover, the proteomics examination of splenic T lymphocytes also confirmed that hASCs/CCR7 decreased the proteins related to cytokinesis, lymphocyte proliferation, differentiation and apoptotic process. In conclusion, our present study demonstrated that targeted migration of hASCs/CCR7 to SLOs highly intensify their in vivo immunomodulatory effect in VCA model for the first time. We believe this SLOs targeting strategy may improve the clinical theraputic efficacy of hASC for allogeneic and autogeneic immune disease. SIGNIFICANCE STATEMENT: Targeted migration after infusion determined their immunoregulatory efficiency of hASCs in vivo. Secondary lymphoid organs (SLOs) are sites for immue initiation and ideal sites for immune tolerance induction. CCR7 can guide hASCs migrating to the T cell aggression area in SLOs. In a rat VCA model, hASCs/CCR7 infusion potently prolonged grafts' survival time. The altered axis of Th1/Th2 and Tregs/Th17 in SLOs and proteomic profile of splenic T lymphocyte explained the down-regulated rejection response. The specific targeting of therapeutic agents particles or drugs to SLOs provides new insight for future clinical applications in the allo-immune and auto-immune diseases. © AlphaMed Press 2019.

16.
Clin Chim Acta ; 498: 135-142, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31442449

RESUMO

BACKGROUND: The lack of rapid and efficient diagnostic methods has been one of the most frustrating challenges in controlling the pulmonary tuberculosis (TB) epidemic. This study was aimed to identify novel non-invasive biomarkers for pulmonary TB. METHODS: The subjects in this study were divided into four groups: the pulmonary TB group, the community-acquired pneumonia (CAP) group, the lung cancer (LC) group, and the normal control (NC) group. Plasma small molecule metabolites were investigated in each group by using ultra-high performance liquid chromatography coupled with Q Exactive mass spectrometry. Multivariate statistical methods and bioinformatics were used to analyze the data. RESULTS: We identified three differential plasma metabolites such as, Xanthine, 4-Pyridoxate and d-glutamic acid in the pulmonary TB group, compared to the other groups (CAP, LC and NC). The pathway enrichment analysis indicated that the energy source in pulmonary TB was multi-center, which might be involved in maintaining the reproductive ability and virulence of Mycobacterium tuberculosis. CONCLUSION: The results suggested that Xanthine, 4-Pyridoxate, and d-glutamic acid may serve as potential biomarkers for pulmonary TB. The present study provides experimental basis for developing potential biomarkers of pulmonary TB.

17.
J Agric Food Chem ; 67(36): 10165-10173, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31398024

RESUMO

Chin-brick tea polysaccharide conjugates (TPC-C) were prepared to study their emulsion capabilities. Interfacial tension and the effects of some factors, such as storage time, metal ion concentrations (Na+, Ca2+), pH (2.0-8.0), and heat treatment (70-100 °C) on the emulsions stabilized by TPC-C were studied. The interfacial tension of TPC-C (10.88 mN/m) was lower than that of gum arabic (15.18 mN/m) at a concentration of 0.08%. As the TPC-C concentration increased from 0.1 to 3.0 wt %, the mean particle diameter (MPD) (d32) of emulsions stabilized by TPC-C decreased from 1.88 to 0.16 µm. Furthermore, at a concentration of 0.5 wt % or higher, the MPD (d32) of emulsions stabilized by TPC-C at 25 and 60 °C for 10 days was between 0.20 and 0.50 µm. In the tested pH conditions from 2.0 to 8.0, the MPD (d32) of emulsions stabilized by 2.0 wt % TPC-C was less than 0.20 µm. At Na+ concentration conditions between 0.10 and 0.50 mol/L, the MPD (d32) of emulsions was between 0.19 and 0.20 µm, and the zeta potential values varied from -34.10 to -32.60 mV. However, with an increasing Ca2+ concentration from 0.01 to 0.05 mol/L, the MPD (d32) of emulsions was between 0.20 and 21.65 µm, and the zeta potential raised sharply from -34.10 to -28.46 mV. The emulsions stabilized by TPC-C have a decent storage stability after a high-temperature heat treatment. Overall, tea polysaccharide conjugates strongly stabilized the emulsions, which support their new application as natural emulsifiers.

18.
Cells ; 8(8)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412678

RESUMO

In recent decades, the biomedical applications of mesenchymal stem cells (MSCs) have attracted increasing attention. MSCs are easily extracted from the bone marrow, fat, and synovium, and differentiate into various cell lineages according to the requirements of specific biomedical applications. As MSCs do not express significant histocompatibility complexes and immune stimulating molecules, they are not detected by immune surveillance and do not lead to graft rejection after transplantation. These properties make them competent biomedical candidates, especially in tissue engineering. We present a brief overview of MSC extraction methods and subsequent potential for differentiation, and a comprehensive overview of their preclinical and clinical applications in regenerative medicine, and discuss future challenges.

19.
Mol Cell ; 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31377117

RESUMO

Interferon gamma (IFN-γ), critical for host defense and tumor surveillance, requires tight control of its expression. Multiple cis-regulatory elements exist around Ifng along with a non-coding transcript, Ifng-as1 (also termed NeST). Here, we describe two genetic models generated to dissect the molecular functions of this locus and its RNA product. DNA deletion within the Ifng-as1 locus disrupted chromatin organization of the extended Ifng locus, impaired Ifng response, and compromised host defense. Insertion of a polyA signal ablated the Ifng-as1 full-length transcript and impaired host defense, while allowing proper chromatin structure. Transient knockdown of Ifng-as1 also reduced IFN-γ production. In humans, discordant expression of IFNG and IFNG-AS1 was evident in memory T cells, with high expression of this long non-coding RNA (lncRNA) and low expression of the cytokine. These results establish Ifng-as1 as an important regulator of Ifng expression, as a DNA element and transcribed RNA, involved in dynamic and cell state-specific responses to infection.

20.
Echocardiography ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31393630

RESUMO

OBJECTIVES: The purpose of this study was to assess the factors influencing the late diastolic vortex in normal and abnormal ventricles. METHODS: Color Doppler data in left ventricle (LV) were acquired from apical long-axis view and analyzed using vector flow mapping in 57 patients with coronary artery disease, 57 patients with dilated cardiomyopathy, and 53 healthy volunteers. RESULTS: In normals, corrected area and flux of the end-diastolic vortex were positively correlated with transmitral A velocity and heart rate. Subjects with E/A <1 had higher vortex flux than those with E/A >1. Heart rate was the only independent predictor of corrected vortex area (R2  = .170, P = .004), and transmitral A velocity and heart rate were the independent predictors of corrected vortex flux (R2  = .490, P < .001). Patients with various mitral filling patterns showed significant differences in vortex area and flux. The vortex area and flux were positively correlated with transmitral i velocity and a'. Transmitral A velocity was the only independent predictor of corrected vortex area (R2  = .180, P < .001), while transmitral A velocity, heart rate, LV end-systolic short diameter, and end-diastolic long diameter were the independent determinants of corrected vortex flux (R2  = .593, P < .001). CONCLUSIONS: The end-diastolic vortex is formed and mainly affected by the late LV filling. The compensatory atrial contraction may enhance the end-diastolic vortex that facilitates coupling between diastole and systole. LV size can influence the end-diastolic vortex in patients with LV dysfunction and enlargement.

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