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1.
Oncol Rep ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31485632

RESUMO

As a member of the myotubularin family, myotubularin related protein 3 (MTMR3) has been demonstrated to participate in tumor development, including oral and colon cancer. However, little is known about its functional roles in breast cancer. In the present study, the expression of MTMR3 in breast cancer was evaluated by immunohistochemical staining of tumor tissues from 172 patients. Online data was then used for survival analysis from the PROGgeneV2 database. In vitro, MTMR3 expression was silenced in MDA­MB­231 cells via lentiviral shRNA transduction. MTT, colony formation and flow cytometry assays were performed in the control and MTMR3­silenced cells to evaluate the cell growth, proliferation and cell cycle phase distribution, respectively. Western blotting was used to evaluate the protein expression levels of autophagy­related markers. The results demonstrated that the expression of MTMR3 in breast cancer tissues was significantly increased compared with adjacent normal tissues. MTMR3 was highly expressed in triple­negative breast cancer and was associated with disease recurrence. MTMR3 knockdown in MDA­MB­231 cells inhibited cell proliferation and induced cell cycle arrest and autophagy. The present results indicated that MTMR3 may have an important role in promoting the progression of breast cancer, and its inhibition may serve as a promising therapeutic target for breast cancer treatment.

2.
J Stroke Cerebrovasc Dis ; : 104311, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31376998

RESUMO

BACKGROUND: Secondary embolism (SE) during mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is the main reason for incomplete recanalization, while its risk factors are largely unknown. This study addresses a potential relationship between thrombus density on preinterventional computed tomography (CT) and the occurrence of SE. METHODS: We reviewed anterior circulation AIS patients who underwent MT from July 2015 to January 2019 in our center. Thrombus density was measured in Hounsfield Units (HU) on 1-mm and 5-mm preinterventional nonenhanced CT (NECT). Thrombus density, baseline characteristics, procedural, and clinical outcomes were compared between patients with SE and those without SE. Logistic regression was conducted to identified potential risk factors of SE. RESULTS: Sixty-four consecutively patients were included, of whom SE was identified in 16 (25.0%) patients. Compared with those without SE, patients with SE showed a higher thrombus density on both 1-mm (72.85 versus 64.28, P = .005) and 5-mm NECT (60.31 versus 49.71, P < .001), a higher proportion of atrial fibrillation (75.0% versus 45.8%, P = .043), a lower clot burden score (.5 versus 6.0, P = .029), and a higher proportion of front-line contact aspiration strategy (50.0% versus 16.7%, P = .020). Multivariate regression analysis showed that only thrombus density was the independent predictor of SE (for the model including HU values on 1-mm NECT, OR 1.11, 95%CI 1.01-1.23, P = .029; for the model including HU values on 5-mm NECT, OR 1.09, 95%CI 1.02-1.17, P = .018). CONCLUSIONS: Higher thrombus density was the independent predictor for SE. Further studies are needed to investigate its role in the optimization of thrombectomy strategy.

3.
Rev Sci Instrum ; 90(7): 075114, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31370504

RESUMO

Pathophysiological changes of astronauts under space microgravity involve complex factors and require an integrative perspective to fully understand the mechanisms. The readouts from space cell biology experiments strongly depend on the hardware and especially the cell bioreactor that is used in distinct spacecraft. Herein, a specialized cell culture bioreactor is designed for culturing mammalian cells on board the SJ-10 satellite. This hardware focuses mainly on satisfying the requirements of gas exchange, bubble separation, and flow control, as well as their functional and structural integration on cell culture within the technical and environmental constraints of the spacecraft platform under microgravity. A passive bubble separator is constructed and is connected in series to an individual cell culture chamber to remove the bubbles that were produced in orbit during cell growth. A moderate flow rate is preset to provide sufficient mass transfer and low shear stress in a well-designed flow circuit. Together with other modules of temperature control, in situ microscopic imaging, and online imaging acquisition, this novel space cell culture system is successfully used to culture human endothelial cells and rat bone marrow-derived mesenchymal stem cells in the SJ-10 mission. The advantages and shortcomings of the integration design are discussed for this type of the hardware.

4.
Environ Microbiol ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31469494

RESUMO

Despite the essential functions of sedimentary bacterial and fungal communities in biogeochemical cycling, little is known about their biogeographic patterns and driving processes in large rivers. Here we investigated the biogeographic assemblies and co-occurrence patterns of sedimentary bacterial and fungal communities in the Jinsha River, one of the largest rivers in southwestern China. The mainstream of river was divided into upstream, midstream and downstream. The results showed that both bacterial and fungal communities differed significantly among three sections. For both communities, their composition variations in all sites or each river section were controlled by the combination of dispersal limitation and environmental selection, and dispersal limitation was the dominant factor. Compared with bacteria, fungi had stronger dispersal limitation. Co-occurrence network analyses revealed higher network connectivity but a lower proportion of positive interaction in the bacterial than fungal network at all sites. In particular, the keystone species belonging to bacterial phyla Proteobacteria and Firmicutes and fungal phyla Ascomycota and Chytridiomycota may play critical roles in maintaining community function. Together, these observations indicate that fungi have a stronger dispersal limitation influence and less network connectivity than bacteria, implying different community assembly mechanisms and ecological functions between bacteria and fungi in large rivers. This article is protected by copyright. All rights reserved.

5.
Med Phys ; 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31444798

RESUMO

PURPOSE: Respiratory motion correction is necessary for the quantitative analysis of liver contrast-enhanced ultrasound (CEUS) image sequences. Most respiratory motion correction methods are based on the dual mode of CEUS image sequences, including contrast and grayscale image sequences. Due to free-breathing motion, the acquired 2-dimensional (2D) ultrasound cine might show the in-plane and out-of-plane motion of tumors. The registration of an entire 2D ultrasound contrast image sequence based on out-of-plane images is ineffective. For the respiratory motion correction of CEUS sequences, the reference image is usually considered the standard for the deletion of any out-of-plane images. Most methods used for the selection of the reference image are subjective in nature. Here, a quantitative method for the selection of an optimal reference image from CEUS image sequences in the B and contrast modes was explored. METHODS: The original high-dimensional ultrasound grayscale image data were mapped into a two-dimensional space using Laplacian Eigenmaps (LE), and K-means clustering was adopted. The center image of the larger cluster with a near-peak contrast intensity was considered the optimal ultrasound reference image. In the ultrasound grayscale image sequence, the images with the maximum correlations to the reference image in the same time interval were selected as the corrected image sequence. The effectiveness of this proposed method was then validated on 18 CEUS cases of VX2 tumors in rabbit livers. RESULTS: Correction smoothed the time-intensity curves (TICs) extracted from the region of interest of the CEUS image sequences. Before correction, the average of the total mean structural similarity (TMSSIM) and the average of the mean correlation coefficient (MCC) from the image sequences were 0.45±0.11 and 0.67±0.16, respectively, and after correction, the average TMSSIM and MCC increased (P<0.001) by 31% to 0.59±0.11 and by 21% to 0.81±0.11, respectively. The average deviation value (DV) index of the TICs from the image sequences prior to correction was 92.16±18.12, and correction reduced the average to 31.71±7.31. The average TMSSIM and MCC values after correction using the mean frame of the reference image (MBMFRI) were clearly lower than those after correction using the proposed method (P<0.001). Moreover, the average DV after correction using the MBMFRI was obviously higher than that after correction using the proposed method (P<0.001). CONCLUSIONS: The breathing frequency of rabbits is notably faster than that of human beings, but the proposed correction method could reduce the effect of the respiratory motion in the CEUS image sequences. The reference image was selected quantitatively, which could improve the accuracy of the quantitative analysis of rabbit liver CEUS sequences using the reference image method based on the current standard of manual selection and the MBMFRI. This easy-to-operate method can potentially be used in both animal studies and clinical applications. This article is protected by copyright. All rights reserved.

6.
Sci Total Environ ; 695: 133785, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31421332

RESUMO

Polybrominated diphenyl ethers (PBDEs) are typical persistent organic pollutants (POPs) in the environment. However, little is known about their effects on phosphorus mineralizing bacteria (PMB) in eutrophic lake sediments, despite the critical role of PMB in phosphorus (P) biogeochemical cycling. In this study, we carried out a 60-day microcosm experiment to understand the effects of 2 and 20 mg kg-1 dry weight decabromodiphenyl ether (BDE-209) on the activity, abundance, diversity, and community composition of PMB in the sediment of Taihu Lake, a typical eutrophic lake in China. The results showed that BDE-209 contamination, regardless of the contamination levels, significantly increased the orthophosphate concentration in overlying water and available phosphorus concentration in sediments on day 60. Such increases may be explained by the stimulatory effects of BDE-209 on alkaline phosphatase (ALP) activity and PMB abundance. Moreover, based on Miseq sequencing of the phoD gene encoding ALP, Actinobacteria was the dominant PMB phylum in all treatments, and BDE-209 significantly increased the diversity of PMB and altered their community composition. In particular, the relative abundances of some PMB genera such as Bradyrhizobium were increased significantly after 60 days of the High treatment. A co-occurrence network analysis further revealed that the high level of BDE-209 contamination strengthened the connectivity and interspecific co-operative relationships in the PMB community. These results will help us to understand the effects of POPs on P biogeochemical cycling in eutrophic lakes and the associated microbial mechanisms.

7.
Mol Med Rep ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31432137

RESUMO

Atherosclerosis is a chronic inflammatory disease, and it is a global clinical problem. The development of new and effective therapeutic targets for atherosclerosis is necessary. A number of microRNAs (miRNAs) have been demonstrated to serve a crucial role in atherosclerosis. However, the role of miRNA (miR)­217 in atherosclerosis remains unclear. Therefore, the aim of the present study was to investigate the role and mechanism of miR­217 in atherosclerosis. The level of miR­217 was detected in the blood of patients with atherosclerosis using reverse transcription­quantitative PCR. THP­1 acute monocytic leukemia cells were treated with oxidized low­density lipoprotein (ox­LDL) to develop an atherosclerotic cell model of macrophages. The relationship between miR­217 and sirtuin 1 (SIRT1) was determined by TargetScan and dual luciferase reporter assay. Cell apoptosis was measured by flow cytometry. Production of pro­inflammatory factors and triglyceride (TG) and total cholesterol (TC) levels were also determined. The results demonstrated that miR­217 was significantly upregulated in atherosclerosis. SIRT1 was demonstrated to be a direct target of miR­217 and was downregulated in atherosclerosis. Downregulation of miR­217 significantly inhibited ox­LDL­induced TG and TC level increase, cell apoptosis and the upregulation of the pro­inflammatory factors tumor necrosis factor α, interleukin (IL)­6 and IL­1ß. Additionally, the SIRT1/AMP­activated protein kinase α/NF­κB pathway was at least partially involved in modulating the effects of miR­217 inhibition on THP­1 cells treated with ox­LDL. In addition, the effects of miR­217 downregulation on ox­LDL­treated THP­1 cells were eliminated by SIRT1 silencing. In conclusion, the results of the present study indicated that miR­217 downregulation may relieve atherosclerosis through the inhibition of macrophage apoptosis and inflammatory response by targeting SIRT1.

8.
Cytotechnology ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31410746

RESUMO

Oleanolic acid (OA), a potential drug for diabetic nephropathy (DN) treatment was found to downregulate the expression of microRNA (miR). The research aimed to investigate the effect of OA on autophagy mediated through miR-142-5p targeted PTEN signal. NRK-52E cells were cultured under normal or high glucose condition. DN model were induced by intravenous injection with streptozotocin (55 mg/kg). Renal fibrosis mice were detected by hematoxylin and eosin (HE) staining, Masson staining and immunohistochemistry assay. TargetScan and dual-luciferase reporter assay system was used to detect the target of miR-142-5p. Expression levels of microRNA and proteins were analyzed by real-time PCR and western blotting. Autophagy was decreased in the progression of renal fibrosis in diabetic nephropathy mice (in vivo) and in high glucose-induced NRK-52E cells (rat kidney epithelial cells) (in vitro) as the expression ofLC-3I and LC-3II (indicators of autophagy) were decreased mice MiR-142-5p was unregulated and PTEN was down-regulated in kidney mice and high glucose-induced NRK-52E cells. Targetscan prediction revealed that PTEN was a target of miR-142-5p. OA restricted HG-induced NRK-52E cell fibrosis through inhibition of miR-142-5p to promote PTEN expression and autophagy levels. To sum up, the research indicated that OA promoted autophagy through inhibition of PI3K/AKT/mTOR pathway. OA alleviated diabetic renal fibrosis by increasing autophagy through regulation of miR-142-5p/PTEN via PI3K/AKT/mTOR pathway in NRK-52E cells.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117433, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31390579

RESUMO

Detecting NAA in food has drawn intense attention as it has imposed significant threat to people's health and the growth of food industry. Over the past few years, great importance has been attached to the application of copper nanomaterials as fluorescent probe to food and environmental detection. Here, the simple, rapid, cost effective and water soluble fluorescent copper nanoparticles were synthesized with chemical reduction sonochemical assisted method for highly selective and sensitive detection of α-naphthaleneacetic acid (NAA) by using 2-mercaptobenzothiazole (MBT) as a protecting agent and polyvinylpyrrolidone (PVP) as a stabilizing agent (MBT-PVP CuNPs). The resultant CuNPs has a spherical shape with an average diameter of 10-15 nm and strong fluorescent pink emission characteristic peak at 580 nm upon 334 nm excitation. Interestingly, upon the addition of NAA, the fluorescence of MBT-PVP CuNPs can be effectively quenched for the reason that NAA could interact with MBT via hydrogen bonding and conform copper-NAA clathrate with Cu+ via coordination bond, which shows a good linearity in the range of NAA from 0.5 to 50 µM and with a detection limit of 9.6 nM. Moreover, the prepared probe has good selectivity for NAA detection over other co-existing molecules. It is worth mentioning that this method has been successfully applied to authentic comestible sample analysis and obtained satisfying and promising results, which indicates that this strategy is likely to have a promising application potential for NAA detection in the field of food safety.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31410962

RESUMO

A nanoemulsion with a porphyrin shell (NewPS) was created by the self-assembly of porphyrin salt around an oil core. The NewPS system has excellent colloidal stability, is amenable to different porphyrin salts and oils, and is capable of co-loading with chemotherapeutics. The porphyrin salt shell enables porphyrin-dependent optical tunability. The NewPS consisting of pyropheophorbide a mono-salt has a porphyrin shell of ordered J-aggregates, which produced a narrow, red-shifted Q-band with increased absorbance. Upon nanostructure dissociation, the fluorescence and photodynamic reactivity of the porphyrin monomers are restored. The spectrally distinct photoacoustic imaging (at 715 nm by intact NewPS) and fluorescence increase (at 671 nm by disrupted NewPS) allow the monitoring of NewPS accumulation and disruption in mice bearing KB tumors to guide effective photodynamic therapy. Substituting the oil core with Lipiodol affords additional CT contrast, whereas loading paclitaxel into NewPS facilitates drug delivery.

11.
Biomaterials ; 222: 119420, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31445322

RESUMO

We have constructed Herceptin-conjugated, paclitaxel (PTX) loaded, PCL-PEG worm-like nanocrystal micelles (PTX@PCL-PEG-Herceptin) for the combinatorial therapy of HER2-positive breast cancer that exploit the specific targeting of Herceptin to HER2-positive breast cancer cells. Firstly, amphiphilic PCL2000-MPEG2000 and PCL5000-PEG2000-CHO were selected as the optimized matrix to wrap PTX that self-assembled into worm-like micelles with internal nanocrystal structures (PTX@PCL-PEG). Then the aldehydes of PCL5000-PEG2000-CHO exposed on the outside surface of PTX@PCL-PEG were utilized to react with the primary amines of Herceptin and formed stable, carbon-nitrogen single linkers (-C-N-) between the antibodies and nanoparticles. This study shows PTX@PCL-PEG-Herceptin remained relatively stable in the circulation and in the tumor microenvironment, and rapidly targeted and entered into the HER2-overexpressing tumor cells while sparing normal tissues from the toxic effects. PTX@PCL-PEG-Herceptin shrank the tumors and prolonged survival time in a SKBR-3-tumor-xenograft, nude mice model more effectively than TAXOL®, PTX@PCL-PEG, Herceptin+TAXOL® and Herceptin+PTX@PCL-PEG. Mechanistic studies showed that PTX@PCL-PEG-Herceptin entered into the HER2-positive tumor cells through the caveolin-mediated pathway. The conjugated Herceptin greatly enhanced the binding ability of the nanoparticle to the targeted SKBR-3 cells. This novel strategy provides a rational and simple antibody-conjugated-nanoparticle platform for the clinical application of combinatorial anticancer treatment.

12.
J Toxicol Sci ; 44(8): 523-533, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31378763

RESUMO

Stephanthraniline A (STA) is a C21 steroidal aglycone isolated from the stem of Stephanotis mucronata (Blanco) Merr. that exerts growth inhibition in human colon cancer cells. However, the intracellular molecular mechanisms whereby this occurs have not been well characterized. In this study, we found that STA significantly inhibits the growth of HCT116 colon cancer cells in a time- and concentration-dependent manner. The inhibitory effect of STA on cell growth was related to the induction of apoptosis. Activated caspase-3, caspase-8 and caspase-9, along with a decreased Bcl-2/Bcl-x ratio and loss of mitochondrial membrane potential (Δψm), were observed in response to STA treatment. Furthermore, treatment of HCT116 cells with STA resulted in G0/G1 phase cell cycle arrest accompanied by decreased mRNA levels of cyclin-dependent kinase 4 (CDK4), p21 and c-myc. Additionally, the inhibition of Akt signaling and activation of p38 signaling were observed after treatment with STA in HCT116 cells. These findings indicate that STA inhibits HCT116 cell growth by promoting apoptosis, the dysregulation of mitochondrial function, and cell cycle arrest.

13.
J Alzheimers Dis ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31424401

RESUMO

Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer's disease (AD). It is shown that apoE4 preferentially undergoes aberrant cleavage in neurons, yielding neurotoxic C-terminal-truncated apoE4 fragment. Endoplasmic reticulum (ER) stress has also been known to be involved in the pathogenesis of AD. However, little is known about the contribution of ER stress to the neurotoxicity of apoE4 fragment. In the present study, we established the neuron-specific expression human C-terminal-truncated apoE4(1-272) fragment transgenic mice and also transfected apoE4(1-272) fragment in neuroblastoma N2a cells. We found that human apoE4(1-272) fragment could trigger ER stress as evidenced by increasing the expression of ER stress markers both in vivo and in vitro. Meanwhile, the apoE4(1-272) transgenic mice presented obviously AD-like neuropathological changes, including the impairment of spatial learning and memory, prominent axonal morphological changes, and hyperphosphorylation of tau. At the same time, we also found that glycogen synthase kinase-3 activities were significantly increased. Furthermore, these neuropathological changes, especially tau hyperphosphorylation and axonal transport impairment, were significantly rescued by the ER stress protector 4-phenylbutyric acid (4-PBA) in apoE4(1-272)-transfected N2a cells. Pretreatment with 4-PBA not only decreased the protein expression of immunoglobulin binding protein (BiP) and C/EBP-homologous protein (CHOP), but also significantly reversed these defects in axonal transport. These results suggested that the neurotoxic effects of apoE4(1-272) fragment found in AD subjects, at least in part, through triggering ER stress and inducing tau hyperphosphorylation, led to the enduring impairment of axonal transport.

14.
Biochem Biophys Res Commun ; 516(1): 307-312, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31256938

RESUMO

As a novel type of mesenchymal stem cell, induced pluripotent stem cell-derived mesenchymal stem cells (iPMSCs) have huge potential for cell therapy. iPMSCs exhibited the typical characteristics of MSCs, whereas the tri-lineage differentiation potential is limited, especially the adipogenic propensity. Here, to reveal the molecular mechanism we carried out the epigenetic comparisons between the iPMSCs and the bone marrow-derived mesenchymal stem cells (BMSCs) and embryonic stem cell-derived mesenchymal stem cells (EMSCs). We found that the iPMSCs was significantly higher than the BMSCs in terms of genome-wide DNA methylation. Meanwhile, the adipogenic gene PPARγ promoter region existed hypermethylation. In addition, compared with EMSCs and BMSCs, iPMSCs had significant differences in the histones epigenetic modification of methylation and acetylation, especially high levels of histone 27 lysine trimethylation (H3K27me3). Furthermore, the epigenetic modifiers Decitabine and EPZ6438 effectively upregulated the gene expression of PPARγ and promoted the adipogenic differentiation of iPMSCs via chromatin remodeling. Taken together, our findings set new metrics to the applications for improving the efficiency and the therapeutic potential of iPMSCs.

15.
Europace ; 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31280323

RESUMO

AIMS: Atrial fibrosis contributes to arrhythmogenesis in atrial fibrillation and can be detected by MRI or electrophysiological mapping. The current study compares the spatial correlation between delayed enhancement (DE) areas to low-voltage areas (LVAs) and to arrhythmogenic areas with spatio-temporal dispersion (ST-Disp) or continuous activity (CA) in atrial fibrillation (AF). METHODS AND RESULTS: Sixteen patients with persistent AF (nine long-standing) underwent DE-magnetic resonance imaging (1.25 mm × 1.25 mm × 2.5 mm) prior to pulmonary vein isolation. Left atrial (LA) voltage mapping was acquired in AF and the regional activation patterns of 7680 AF wavelets were analysed. Sites with ST-Disp or CA were characterized (voltage, duration) and their spatial relationship to DE areas and LVAs <0.5 mV was assessed. Delayed enhancement areas and LVAs covered 55% and 24% (P < 0.01) of total LA surface, respectively. Delayed enhancement area was present at 61% of LVAs, whereas low voltage was present at 28% of DE areas. Most DE areas (72%) overlapped with atrial high-voltage areas (>0.5 mV). Spatio-temporal dispersion and CA more frequently co-localized with LVAs than with DE areas (78% vs. 63%, P = 0.02). Regional bipolar voltage of ST-Disp vs. CA was 0.64 ± 0.47 mV vs. 0.58 ± 0.51 mV. All 28 ST-Disp and 56 CA areas contained electrograms with prolonged duration (115 ± 14 ms) displaying low voltage (0.34 ± 0.11 mV). CONCLUSION: A small portion of DE areas and LVAs harbour the arrhythmogenic areas displaying ST-Disp or CA. Most arrhythmogenic activities co-localized with LVAs, while there was less co-localization with DE areas. There is an important mismatch between DE areas and LVAs which needs to be considered when used as target for catheter ablation.

16.
Tree Physiol ; 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31274160

RESUMO

Rhizobia and legume plants are famous mutualistic symbiosis partners who provide nitrogen nutrition to natural environment. Rhizobial type III secretion systems (T3SSs) deliver effectors that manipulate the metabolism of eukaryotic host cells. Mesorhizobium amorphae CCNWGS0123 (GS0123) contains two T3SS gene clusters, T3SS-I and T3SS-II. T3SS-I contains all the basal components for an integrated T3SS, and the expression of T3SS-I genes is up-regulated in the presence of flavonoids. In contrast, T3SS-II lacks the primary extracellular elements of T3SSs, and the expression of T3SS-II genes is down-regulated in the presence of flavonoids. Inoculation tests on Robinia pseudoacacia displayed considerable differences in gene expression patterns and levels among roots inoculated with GS0123 and T3SS-deficient mutant (GS0123ΔT1, GS0123ΔT2 or GS0123ΔS). Compared with the GS0123-inoculated plants, GS0123ΔT1-inoculated roots formed very few infection threads and effective nodules, while GS0123ΔT2-inoculated roots formed a little fewer infection threads and effective nodules with increased numbers of bacteroids enclosed in one symbiosome. Moreover, almost no infection threads or effective nodules were observed in GS0123ΔS-inoculated roots. In addition to evaluations of plant immunity signals, we observed that the coexistence of T3SS-I and T3SS-II promoted infection by suppressing host defense response in ROS defense response pathway. Future studies should focus on identifying rhizobial T3SS effectors and their host target proteins.

17.
J Clin Lab Anal ; : e22954, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31257675

RESUMO

BACKGROUND: This study aimed to explore the correlation of circular RNA HECT domain E3 ubiquitin protein ligase 1 (circRNA HECTD1) expression with disease risk, disease severity, inflammation, and recurrence of acute ischemic stroke (AIS). METHODS: A total of 160 initial AIS patients and 160 controls were enrolled in this study. Peripheral blood mononuclear cells of AIS patients and controls were separated from blood samples to detect circRNA HECTD1 expression by RT-qPCR. Inflammatory cytokines in serum of AIS patients were measured by ELISA. Furthermore, the National Institutes of Health Stroke Scale (NIHSS) score was used to evaluate disease severity of AIS patients. Additionally, disease recurrence was documented during follow-up, and recurrence-free survival (RFS) was calculated. RESULTS: CircRNA HECTD1 expression was higher in AIS patients than that in controls, and the receiver operating characteristic (ROC) curve revealed that circRNA HECTD1 expression was of a good value in distinguishing AIS patients from controls with area under the curve (AUC) of 0.814 (95% CI: 0.768-0.859). In AIS patients, circRNA HECTD1 expression was positively correlated with NIHSS score, CRP, and pro-inflammatory cytokines. CircRNA HECTD1 expression was increased in AIS recurrence patients compared to non-recurrence patients, and further, ROC curve analysis disclosed that circRNA HECTD1 expression predicted higher risk of AIS recurrence (AUC: 0.694, 95% CI: 0.586-0.801). Additionally, circRNA HECTD1 expression was negatively correlated with RFS. CONCLUSIONS: CircRNA HECTD1 expression correlates with higher disease risk, disease severity, inflammation, and recurrence of AIS.

18.
Acad Radiol ; 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31324580

RESUMO

RATIONALE AND OBJECTIVES: To describe the application of time maximum intensity projection CTA (t-MIP CTA) in acute ischemic stroke and compare t-MIP CTA and single-phase CTA (sCTA) in assessing collateral circulation and predicting prognosis. MATERIALS AND METHODS: Twenty-nine acute ischemic stroke patients who underwent one-stop CT angiography (CTA)-CT perfusion scan were reviewed retrospectively. sCTA and t-MIP CTA were developed by CT perfusion scanning data. Image quality and collateral circulation were compared between the sCTA and t-MIP CTA groups. CT attenuation values, image noise, signal to noise , contrast to noise, and subjective image quality were obtained and compared between these two groups. The correlations of clinical prognosis and infarct volume with collateral status on t-MIP CTA and sCTA were analyzed, separately. Receiver operating characteristic curve was used to reveal the sensitivity and specificity of t-MIP CTA and sCTA in predicting outcome. RESULTS: All images exhibited good quality for diagnosis. In objective evaluation, the noise level of t-MIP CTA was significantly lower than that of sCTA (p < 0.001). Vascular attenuation (signal to noise and contrast to noise) of t-MIP were higher than those of sCTA (all, p < 0.001). The collateral status on t-MIP CTA and sCTA were both negatively correlated with modified Rankin Scale scores (t-MIP CTA, r = -0.709, p < 0.001; sCTA, r = -0.551, p = 0.024) and the final infarction volume (t-MIP CTA, r = -0.716, p = 0.001; sCTA, r = -0.629, p = 0.003). t-MIP CTA was better for predicting prognosis (AUC, 0.956; sensitivity, 0.917; specificity, 0.941; p < 0.001) than sCTA (AUC, 0.824; sensitivity, 0.500; specificity, 0.941; p = 0.003). CONCLUSION: In comparison with sCTA, t-MIP images showed higher image quality of intracranial vascularity and MIP could reveal vascular occlusion and evaluate collateral circulation more accurately. It was speculated that t-MIP could predict the prognosis more precisely.

19.
Drug Des Devel Ther ; 13: 1957-1967, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354241

RESUMO

Background: The authors have recently designed a new compound bisperoxovandium (pyridin-2-squaramide) [bpV(pis)] and verified that bpV(pis) confers neuroprotection through suppressing PTEN and activating ERK1/2, respectively. Intracerebral hemorrhage (ICH) is the second most common cause of stroke and has severe clinical outcome. In this study, we investigate the effect of bpV(pis) in ICH model both in vivo and in vitro. Materials and methods: The novel drug bpV(pis) was synthesized in the Faculty of Pharmacy, Wuhan University School of Medicine. An ICH model was generated on both SD rats and cells. bpV(pis) was injected into intracerebroventricular or culture media. Western blotting was applied to test the signal pathway. To determine the effect of bpV(pis) on PTEN inhibition and ERK1/2 activation, we measured the phosphorylation level of AKT (a direct downstream target of PTEN that negatively regulates AKT) and ERK1/2. FJC, MTT, and LDH were applied to measure the cell viability. Neurobehavioral tests were performed to measure the effect of bpV(pis). Results: The in vivo results showed that intracerebroventricular administration of bpV(pis) significantly alleviates hematoma, the damage of brain-blood barrier and brain edema. The in vitro results demonstrated that bpV(pis) treatment reduces ICH-induced neuronal injury. Western blotting results identified that bpV(pis) exerts a neuroprotective effect by significantly increasing the phosphorylation level of AKT and ERK1/2 after experimental ICH. Neurobehavioral tests indicate that bpV(pis) promotes functional recovery in ICH animals. Conclusion: This study provides first and direct evidence for a potential role of bpV(pis) in ICH therapy.

20.
Ren Fail ; 41(1): 600-606, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31282239

RESUMO

Background: The presence of simple renal cyst (SRC) has been associated to renal dysfunction, but the results were inconsistent. Accordingly, we conducted a longitudinal cohort study to explore the association between SRC and kidney damage. Methods: A total of 4274 adults (aged 45.4 ± 13.6 years) without chronic kidney disease at baseline were enrolled in 2008. SRC was assessed by ultrasonography. Logistic regression analysis were applied to explore the relationships between SRC and indicators of kidney damage (proteinuria and renal insufficiency), and also with relatively rapid decline in renal function (defined as the lowest quartile of △eGFR). Results: During 5 years of follow-up, participants in the SRC group had higher incidence of proteinuria (5.2% versus 2.4%, p = 0.004) and renal insufficiency (3.8% versus 0.97%, p < 0.001) compared with control group. SRC was correlated with proteinuria (OR 2.24; 95% CI 1.34-3.75) and renal insufficiency (OR 4.0; 95% CI 2.11-7.58) in univariable analysis, despite that the correlation was not significant after adjusted for traditional kidney disease risk factors. Furthermore, after adjusted for potential confounders, maximum diameter of the cyst (≥2.2 cm) was significantly associated with rapid decline in renal function (OR 2.19; 95% CI 1.24-3.87). Conclusions: Participants with SRC may be associated with higher incidence of proteinuria and renal insufficiency. This relationship may be obscured by age and other traditional risk factors. Higher diameter of the cysts contributed to more rapid decline in renal function of SRC participants.

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