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1.
Nucleic Acids Res ; 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32086516

RESUMO

To sustain iron homeostasis, microorganisms have evolved fine-tuned mechanisms for uptake, storage and detoxification of the essential metal iron. In the human pathogen Aspergillus fumigatus, the fungal-specific bZIP-type transcription factor HapX coordinates adaption to both iron starvation and iron excess and is thereby crucial for virulence. Previous studies indicated that a HapX homodimer interacts with the CCAAT-binding complex (CBC) to cooperatively bind bipartite DNA motifs; however, the mode of HapX-DNA recognition had not been resolved. Here, combination of in vivo (genetics and ChIP-seq), in vitro (surface plasmon resonance) and phylogenetic analyses identified an astonishing plasticity of CBC:HapX:DNA interaction. DNA motifs recognized by the CBC:HapX protein complex comprise a bipartite DNA binding site 5'-CSAATN12RWT-3' and an additional 5'-TKAN-3' motif positioned 11-23 bp downstream of the CCAAT motif, i.e. occasionally overlapping the 3'-end of the bipartite binding site. Phylogenetic comparison taking advantage of 20 resolved Aspergillus species genomes revealed that DNA recognition by the CBC:HapX complex shows promoter-specific cross-species conservation rather than regulon-specific conservation. Moreover, we show that CBC:HapX interaction is absolutely required for all known functions of HapX. The plasticity of the CBC:HapX:DNA interaction permits fine tuning of CBC:HapX binding specificities that could support adaptation of pathogens to their host niches.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32049549

RESUMO

Excessive exposure of the eye to ultraviolet B light (UVB) leads to corneal edema and opacification because of the apoptosis of the corneal endothelium. Our previous study found that nicotinamide (NIC), the precursor of nicotinamide adenine dinucleotide (NAD), could inhibit the endothelial-mesenchymal transition and accelerate healing the wound to the corneal endothelium in the rabbit. Here we hypothesize that NIC may possess the capacity to protect the cornea from UVB-induced endothelial apoptosis. Therefore, a mouse model and a cultured cell model were used to examine the effect of NAD+ precursors, including NIC, nicotinamide mononucleotide (NMN) and NAD, on the UVB-induced apoptosis of corneal endothelial cells (CECs). The results showed that UVB irradiation caused apparent corneal edema and cell apoptosis in mice, accompanied by reduced levels of NAD+ and its key biosynthesis enzyme, nicotinamide phosphoribosyltransferase (NAMPT), in the corneal endothelium. However, the subconjunctival injection of NIC, NMN or NAD+ effectively prevented UVB-induced tissue damage and endothelial cell apoptosis in the mouse cornea. Moreover, pretreatment using NIC, NMN and NAD+ increased the survival rate and inhibited the apoptosis of cultured human CECs irradiated by UVB. Mechanistically, pretreatment using NIC recovered the AKT activation level and decreased the BAX/BCL-2 ratio. In addition, the capacity of NIC to protect CECs was fully reversed in the presence of the AKT inhibitor LY294002. Therefore, we conclude that NAD+ precursors can effectively prevent the apoptosis of the corneal endothelium through reactivating AKT signaling; this represents a potential therapeutic approach for preventing UVB-induced corneal damage.

3.
Pest Manag Sci ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31951096

RESUMO

BACKGROUND: Parasitoid venom is composed of a complex mixture of various active substances with different biological functions and is injected in the host during the parasitoid oviposition. Anastatus japonicus (Hymenoptera: Eupelmidae) is an egg parasite of Tessaratoma papillosa (Hemiptera: Tessaratomidae). Although the venom of this egg parasitoid plays an important role in the parasitic process, relatively little work has been done to address the mechanism. RESULTS: In the present study, proteomic analysis was performed to identify the proteins that play an important role in the parasitic process of A. japonicus. A total of 2084 proteins were identified, including 81 putative venom proteins, most of which were identified as Hexamerin, Chitinase 2, Calreticulin, Heat shock protein 83-like, Serine protease, Arginine kinase, Phosphoserine aminotransferase and Actin protein. Together the before (Be) and after (Af) parasitization venom contains 1628 proteins, including 212 DEPs with 181 and 31 significantly up-regulated and down-regulated respectively. In addition, 10 differentially expressed proteins (DEPs) with fold change ≥8.71 were subjected to RT-qPCR to validate the proteomic data. The differential expression analysis revealed that nine proteins were specifically present in the pre-parasitic venom, whereas 26 proteins were specific to the post-parasitic treatments. Results of RT-qPCR analysis showed high expression of the selected DEPs which further validated our proteomics data. CONCLUSION: These new proteomic data greatly enrich our current knowledge about key venom proteins associated with parasitic process in A. japonicus and contribute to better understanding of the parasitic mechanisms leading to the development of new biological control strategies. © 2020 Society of Chemical Industry.

4.
ESC Heart Fail ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31965727

RESUMO

AIMS: RBP4 is an adipokine with adverse effects on cardiovascular system. Increased circulating retinol-binding protein 4 (RBP4) has been linked to chronic heart failure (CHF). However, whether elevated RBP4 is correlated with a poor prognosis in elderly patients with CHF remains unclear. The aim of this study was to evaluate the prognostic value of serum RBP4 in elderly patients with CHF. METHODS AND RESULTS: We enrolled 934 consecutive elderly patients (aged 60 years and older) with CHF and 138 age-matched and sex-matched control subjects in a prospective cohort study and explored the association of serum RBP4 levels with the clinical outcomes using multivariate Cox regression analyses. Serum RBP4 levels were elevated in CHF patients when compared with controls (46.66 ± 12.38 µg/mL vs. 40.71 ± 7.2 µg/mL, P < 0.001). Patients with the highest RBP4 concentrations had higher N terminal pro brain natriuretic peptide (NT-proBNP) levels but lower left ventricular eject fraction (LVEF) and estimated glomerular filtration rate (P < 0.001). Serum RBP4 levels were increased as the New York Heart Association functional class increased and LVEF decreased (P < 0.001) and were negatively correlated with LVEF (r = -0.154, P < 0.001) but positively correlated with NT-proBNP levels (r = 0.074, P = 0.023). Multivariate Cox regression analysis suggested that log RBP4 was an independent predictor for major adverse cardiac event(s) [hazard ratio (HR) = 2.61, 95% confidence interval (CI) = 1.19-5.70], together with age, male, LVEF, log NT-proBNP, and estimated glomerular filtration rate. Moreover, log RBP4 was also an independent predictor for cardiovascular mortality (HR = 2.24, 95% CI = 1.35-5.39) and CHF rehospitalization (HR = 2.54, 95% CI = 1.09-5.60) even after adjustment for the established adverse prognostic factors for CHF. The Kaplan-Meier survival curves showed that high concentration of RBP4 was a prognostic indicator of major adverse cardiac event(s) in patients with CHF. CONCLUSIONS: Our findings demonstrate for the first time that elevated serum RBP4 is correlated with worse outcome in elderly patients with CHF.

5.
Acta Biomater ; 101: 344-356, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31706041

RESUMO

The primary functions of the conjunctiva embody ocular surface protection and the maintenance of the tear film equilibrium. Severe conjunctival defects such as symblepharon may impair the integrity of ocular surface and cause loss of visual functions. Here we report the use of a decellularized porcine conjunctiva (DPC) for conjunctival reconstruction in rabbit models and in clinic. Our results show that the major xenoantigens are efficiently removed, while abundant matrix components and integrated microstructures are well preserved in the DPC. These characteristics provide mechanical support and favorable histocompatibility for repairing damaged conjunctiva. The DPC application has demonstrated enhanced transplant stability and improved epithelial regeneration in severe ocular surface damage comparing to those of amniotic membrane (AM), the most frequently applied matrix for ocular surface reconstruction nowadays. In order to test the DPC performance in clinic, three patients with pterygium and one patient with symblepharon underwent transplant with DPC. The grafts in all cases were completely re-epithelized and no graft melt or fibroplasia were observed. These results suggest that the strategy we developed is feasible and effective for conjunctival reconstruction and ocular surface repair. STATEMENT OF SIGNIFICANCE: In this study, we adopted an innovative approach to prepare decellularized porcine conjunctiva (DPC). The intricate conjunctiva-specific structures and abundant matrix components were preserved in DPC, which offers favorable mechanical properties for graft. DPC has shown positive effects in ocular surface repair, which has been proven particularly in a rabbit model with severe symblepharon. Reconstructed conjunctiva by DPC exhibited epithelial heterogeneity, extremely resembling that of native conjunctiva. In addition, results from clinical studies were encouraging for pterygium and symblepharon and clinical application of DPC is promising.

6.
Org Lett ; 21(23): 9457-9462, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31755725

RESUMO

Pd-catalyzed regio- and enantioselective allylic etherification of vinylethylene carbonates (VECs) with diols has been developed. By using cooperative catalysts of the chiral palladium complex and triethylborane in mild conditions, the process gave monoetherified and bisetherified polyglycol derivatives with tetrasubstituted stereocenters in high yields with complete regioselectivities and high levels of enantio- and diastereoselectivities.

7.
Org Lett ; 21(22): 9045-9049, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31697086

RESUMO

A useful method for the enantioselective preparation of isoxazoline N-oxides via Pd-catalyzed asymmetric allylic cycloaddition of nitro-containing allylic carbonates has been developed. By using palladium complex in situ generated from Pd2(dba)3·CHCl3 and phosphoramidite L2 as a catalyst under mild conditions, the transformation afforded vinylated isoxazoline N-oxides in high yields with acceptably high enantioselectivities.

8.
Org Lett ; 21(23): 9452-9456, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31702930

RESUMO

An efficient method for the enantioselective synthesis of cyclic ureas has been developed through Pd-catalyzed asymmetric allylic cycloaddition of readily accessible nitrogen-containing allylic carbonates with isocyanates. By using a palladium complex in situ generated from Pd2(dba)3·CHCl3 and phosphoramidite L1 or L3 as a ligand under mild reaction conditions, the process afforded imidazolidinones and tetrahydropyrimidinones with high yields and high levels of enantioselectivities.

9.
Front Microbiol ; 10: 2311, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31649650

RESUMO

Pathogen-pathogen interactions in polymicrobial infections are known to directly impact, often to worsen, disease outcomes. For example, co-infection with Pseudomonas aeruginosa and Aspergillus fumigatus, respectively the most common bacterial and fungal pathogens isolated from cystic fibrosis (CF) airways, leads to a worsened prognosis. Recent studies of in vitro microbial cross-talk demonstrated that P. aeruginosa-derived volatile sulfur compounds (VSCs) can promote A. fumigatus growth in vitro. However, the mechanistic basis of such cross-talk and its physiological relevance during co-infection remains unknown. In this study we combine genetic approaches and GC-MS-mediated volatile analysis to show that A. fumigatus assimilates VSCs via cysteine (CysB)- or homocysteine (CysD)-synthase. This process is essential for utilization of VSCs as sulfur sources, since P. aeruginosa-derived VSCs trigger growth of A. fumigatus wild-type, but not of a ΔcysBΔcysD mutant, on sulfur-limiting media. P. aeruginosa produces VSCs when infecting Galleria mellonella and co-infection with A. fumigatus in this model results in a synergistic increase in mortality and of fungal and bacterial burdens. Interestingly, the increment in mortality is much greater with the A. fumigatus wild-type than with the ΔcysBΔcysD mutant. Therefore, A. fumigatus' ability to assimilate P. aeruginosa derived VSCs significantly triggers a synergistic association that increases the pathobiology of infection. Finally, we show that P. aeruginosa can promote fungal growth when growing on substrates that resemble the lung environment, which suggests that this volatile based synergism is likely to occur during co-infection of the human respiratory airways.

10.
Curr Protoc Microbiol ; 54(1): e89, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31518062

RESUMO

Aspergillus fumigatus is an opportunistic human pathogenic mold. DNA extraction from this fungus is usually performed by mechanical perturbation of cells, as it possesses a rigid and complex cell wall. While this is not problematic for single isolates, it can be time consuming for large numbers of strains if using traditional DNA extraction procedures. Therefore, in this article we describe a fast and efficient thermal-shock method to release DNA from spores of A. fumigatus and other filamentous fungi without the need for complex extraction methods. This is especially important for high-throughput PCR analyses of mutants in 96- or 384-well formats in a very short period of time without any concern about sample cross-contamination. This method is currently being used to validate the protein-coding gene and non-coding RNA knockout libraries in A. fumigatus generated in our laboratory, and could be used in the future for diagnostics purposes. © 2019 The Authors.

11.
Curr Protoc Microbiol ; 54(1): e88, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31518064

RESUMO

Aspergillus fumigatus is a human pathogen and the principal etiologic agent of invasive and chronic aspergillosis leading to several hundreds of thousands of deaths every year. Very few antifungals are available to treat infections caused by A. fumigatus, and resistance is developing to those we have. Our understanding of the molecular mechanisms that drive pathogenicity and drug resistance have been hampered by the lack of large mutant collections, which limits our ability to perform functional genomics analysis. Here we present a high-throughput gene knockout method that combines a highly reproducible fusion PCR method to enable generation of gene replacement cassettes with a multiwell format transformation procedure. This process can be used to generate 96 null mutants within 5 days by a single person at a cost of less than £18 ($24) per mutant and is being employed in our laboratory to generate a barcoded genome-wide knockout library in A. fumigatus. © 2019 The Authors.

12.
Genomics ; 111(5): 1059-1065, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31533898

RESUMO

The taxonomic status and phylogenetic affinities of Mymaridae and Scelionidae are controversial, based on similarities between these families in the characteristics of adults, larvae, and eggs. In this study, we sequenced the mitochondrial (mt) genomes of representatives from these two families and found that the derived secondary structure of tRNA-Arg was the same in each family due to the absence of the D-stem. The segment of "cox1 trnL2cox2 trnK trnD atp8 atp6 cox3" in Gonatocerus sp. (Mymaridae) is conserved and distinct from those of four other species of Chalcidoidea but similar to that in Proctotrupoidea and Platygastroidea. However, phylogenetic analysis indicated that Gonatocerus sp. was sister group to other species of Chalcidoidea. Comparisons based on complete gene orders may be more useful in a phylogenetic and systematic context, as different branches may exhibit partially homoplastic gene orders.

13.
Magn Reson Imaging ; 64: 160-170, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31301354

RESUMO

Magnetic resonance imaging (MRI) is a flexible medical imaging modality that often lacks reproducibility between protocols and scanners. It has been shown that even when care is taken to standardize acquisitions, any changes in hardware, software, or protocol design can lead to differences in quantitative results. This greatly impacts the quantitative utility of MRI in multi-site or long-term studies, where consistency is often valued over image quality. We propose a method of contrast harmonization, called DeepHarmony, which uses a U-Net-based deep learning architecture to produce images with consistent contrast. To provide training data, a small overlap cohort (n = 8) was scanned using two different protocols. Images harmonized with DeepHarmony showed significant improvement in consistency of volume quantification between scanning protocols. A longitudinal MRI dataset of patients with multiple sclerosis was also used to evaluate the effect of a protocol change on atrophy calculations in a clinical research setting. The results show that atrophy calculations were substantially and significantly affected by protocol change, whereas such changes have a less significant effect and substantially reduced overall difference when using DeepHarmony. This establishes that DeepHarmony can be used with an overlap cohort to reduce inconsistencies in segmentation caused by changes in scanner protocol, allowing for modernization of hardware and protocol design in long-term studies without invalidating previously acquired data.

14.
Biomed Chromatogr ; 33(11): e4638, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31261446

RESUMO

Monitoring gefitinib and its metabolites may help to explore the underlying mechanisms of gefitinib resistance. The concentration of gefitinib and its metabolites in tumor tissues could influence its anticancer activities more than that in the plasma. In the present study, a rapid and specific HPLC-MS/MS method was developed and validated to simultaneously determine gefitinib, M387783, M523595, M537194 and M608236 in tumor tissues of H1975 human lung cancer xenografts of nude mice. The established HPLC-MS/MS method was validated for specificity, linearity, accuracy and precision, matrix effect and recovery, carryover and dilution integrity, and analyte stability. The standard curves were linear (r2 ≥ 0.99) over the range of 0.5-100 ng/mL for M608236 and 1-200 ng/mL for gefitinib, M523595 and M537194 as well as M387783. The accuracy ranged from -8.35 to 6.03% relative error; and the precision was <15% relative standard deviation. Recoveries (87.74-99.96%) and matrix effects (86.60-106.40%) were satisfactory in the biological matrix examined. Stability studies showed that the analytes were stable during the assay procedure and storage. Finally, the validated method was successfully applied to study the pharmacokinetics profiles for gefitinib and its metabolites in nonsmall cell lung cancer (NSCLC) xenograft mouse tumors. Meanwhile, MTT assay showed that gefitinib had a more powerful inhibitory effect than its four major metabolites in H1975 NSCLC cells. This validated HPLC-MS/MS method may be applied to help understand the mechanisms of gefitinib resistance in EGFR-mutant nonsmall cell lung cancer.


Assuntos
Antineoplásicos/análise , Cromatografia Líquida de Alta Pressão/métodos , Gefitinibe/análise , Neoplasias Pulmonares/metabolismo , Espectrometria de Massas em Tandem/métodos , Animais , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Feminino , Gefitinibe/farmacocinética , Xenoenxertos , Modelos Lineares , Camundongos , Camundongos Nus , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
15.
Artigo em Inglês | MEDLINE | ID: mdl-31263454

RESUMO

Adipocytes function as an energy buffer and undergo significant size and volume changes in response to nutritional cues. This adipocyte plasticity is important for systemic lipid metabolism and insulin sensitivity. Accompanying the adipocyte size and volume changes, the mechanical pressure against cell membrane also changes. However, the role that mechanical pressure plays in lipid metabolism and insulin sensitivity remains to be elucidated. Here we show that Piezo1, a mechanically-activated cation channel stimulated by membrane tension and stretch, was highly expressed in adipocytes. Adipose Piezo1 expression was increased in obese mice. Adipose-specific piezo1 knockout mice (adipose-Piezo1-/-) developed insulin resistance, especially when challenged with a high-fat diet (HFD). Perigonadal white adipose tissue (pgWAT) weight was reduced while pro-inflammatory and lipolysis genes were increased in the pgWAT of HFD-fed adipose-Piezo1-/- mice. The adipose-Piezo1-/- mice also developed hepatic steatosis with elevated expression of fatty acid synthesis genes. In cultured adipocytes, Piezo1 activation decreased, while Piezo1 inhibition elevated pro-inflammatory gene expression. TLR4 antagonist TAK-242 abolished adipocyte inflammation induced by Piezo1 inhibition. Thus, adipose Piezo1 may serve as an adaptive mechanism for adipocyte plasticity restraining pro-inflammatory response in obesity.

16.
J Med Primatol ; 48(6): 320-328, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31148186

RESUMO

BACKGROUND: The relatively tiny spinal cord of non-human primate (NHP) causes increased challenge in diffusion tensor imaging (DTI) post-processing. This study aimed to establish a reliable correction strategy applied to clinical DTI images of NHP. METHODS: Six normal and partial spinal cord injury (SCI) rhesus monkeys underwent 3T MR scanning. A correction strategy combining multiple iterations and non-rigid deformation was used for DTI image post-processing. Quantitative evaluations were then conducted to investigate effects of distortion correction. RESULTS: After correction, longitudinal geometric distortion, global distortion, and residual distance errors were all significantly decreased (P < 0.05). Fractional anisotropy at the injured site was remarkably lower than that at the contralateral site (P = 0.0488) and was substantially lower than those at the adjacent superior (P = 0.0157) and inferior (P = 0.0128) areas at the same side. CONCLUSIONS: Our image correction strategy can improve the quality of the DTI images of NHP thoracic cords, contributing to the development of SCI preclinical research.

17.
Magn Reson Imaging ; 64: 132-141, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31247254

RESUMO

Magnetic resonance (MR) images with both high resolutions and high signal-to-noise ratios (SNRs) are desired in many clinical and research applications. However, acquiring such images takes a long time, which is both costly and susceptible to motion artifacts. Acquiring MR images with good in-plane resolution and poor through-plane resolution is a common strategy that saves imaging time, preserves SNR, and provides one viewpoint with good resolution in two directions. Unfortunately, this strategy also creates orthogonal viewpoints that have poor resolution in one direction and, for 2D MR acquisition protocols, also creates aliasing artifacts. A deep learning approach called SMORE that carries out both anti-aliasing and super-resolution on these types of acquisitions using no external atlas or exemplars has been previously reported but not extensively validated. This paper reviews the SMORE algorithm and then demonstrates its performance in four applications with the goal to demonstrate its potential for use in both research and clinical scenarios. It is first shown to improve the visualization of brain white matter lesions in FLAIR images acquired from multiple sclerosis patients. Then it is shown to improve the visualization of scarring in cardiac left ventricular remodeling after myocardial infarction. Third, its performance on multi-view images of the tongue is demonstrated and finally it is shown to improve performance in parcellation of the brain ventricular system. Both visual and selected quantitative metrics of resolution enhancement are demonstrated.

18.
Cell Signal ; 62: 109325, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31132398

RESUMO

Myocardial ischemia-reperfusion injury (MIRI) is recognized as a major cause of morbidity and mortality which is commonly associated with coronary artery disease. In recent studies, annexin A1 gene (ANXA1) has been discovered to be involved in the treatment for MIRI. In this study, the primary focus was on the molecular mechanism of ANXA1 in polymorphonuclear neutrophil (PMN) infiltration and myeloperoxidase (MPO) activity in rats with MIRI. Initially, microarray analysis was carried out in order to identify differentially expressed genes. Moreover, a rat model of MIRI was established for evaluating the expression of ANXA1, signal transducer and activator of transcription 3 (STAT3) and vascular endothelial growth factor (VEGF) in myocardial tissues. Following this, the ANXA1 vector, siRNA-ANXA1, and Stattic (inhibitor of STAT3 signaling pathway) were utilized for analyzing the regulatory role of ANXA1 in physiological indexes, hemodynamic parameters, inflammatory factors, myocardial infarct size, MPO activity, PMN infiltration, and apoptosis of PMNs. Furthermore, the relationship between ANXA1 and STAT3 signaling pathway was analyzed. Initially, a reduction in the expression of ANXA1, STAT3 and VEGF in myocardial tissues of MIRI rats was found. To elaborate, overexpressed ANXA1 inhibited levels of inflammatory factors, the activation of PMN infiltration, reduced the degree of PMN infiltration, and decreased the apoptosis of PMNs. More importantly, down-regulated ANXA1 inhibited the activation of STAT3 signaling pathway, which thereby suppressed VEGF expression. With this all taken into account, the present study presents that up-regulated ANXA1 inhibits PMN infiltration and MPO activity by activation of STAT3 signaling pathway in rats with MIRI.

19.
Aging (Albany NY) ; 11(9): 2762-2786, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31064890

RESUMO

Acute ischemic stroke (AIS) is a major public health problem in China. Impaired angiogenesis plays crucial roles in the development of ischemic cerebral injury. Recent studies have identified that microRNAs (miRNAs) are important regulators of angiogenesis, but little is known the exact effects of angiogenesis-associated miRNAs in AIS. In the present study, we detected the expression levels of angiogenesis-associated miRNAs in AIS patients, middle cerebral artery occlusion (MCAO) rats, and oxygen-glucose deprivation/reoxygenation (OGD/R) human umbilical vein endothelial cells (HUVECs). MiR-191 was increased in the plasma of AIS patients, OGD/R HUVECs, and the plasma and brain of MCAO rats. Over-expression of miR-191 promoted apoptosis, but reduced the proliferation, migration, tube-forming and spheroid sprouting activity in HUVECs OGD/R model. Mechanically, vascular endothelial zinc finger 1 (VEZF1) was identified as the direct target of miR-191, and could be regulated by miR-191 at post-translational level. In vivo studies applying miR-191 antagomir demonstrated that inhibition of miR-191 reduced infarction volume in MCAO rats. In conclusion, our data reveal a novel role of miR-191 in promoting ischemic brain injury through inhibiting angiogenesis via targeting VEZF1. Therefore, miR-191 may serve as a biomarker or a therapeutic target for AIS.

20.
Exp Anim ; 68(3): 341-349, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-30930341

RESUMO

Walking is characterized by repetitive limb movements associated with highly structured patterns of muscle activity. The causal relationships between the muscle activities and hindlimb segments of walking are difficult to decipher. This study investigated these particular relationships and clarified whether they are correlated with speed to further understand the neuromuscular control pattern. Four adult female rhesus monkeys (Macaca mulatta) were selected to record gait parameters while walking on a bipedal treadmill at speeds of 0.2, 0.8, 1.4, and 2.0 km/h. We recorded 3 ipsilateral hindlimb muscles by surface recording. In this study, we calculated the correlations between electromyography (EMG) and kinematic parameters (24 EMG*17 kinematic parameters). Of the 408 calculated coefficients, 71.6% showed significant linear correlations. Significant linear correlations were found between muscle activity, such as burst amplitudes and the integral of muscle activity, and the corresponding kinematic parameters of each joint. Most of these relationships were speed independent (91.7% of all variables). Through correlation analysis, this study demonstrated a causal association between kinematic and EMG patterns of rhesus monkey locomotion. Individuals have particular musculoskeletal control patterns, and most of the relationships between hindlimb segments and muscles are speed independent. The current findings may enhance our understanding of neuromusculoskeletal control strategies.


Assuntos
Macaca mulatta/fisiologia , Músculo Esquelético/fisiologia , Caminhada/fisiologia , Animais , Fenômenos Biomecânicos , Eletromiografia , Feminino
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