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1.
Cell Mol Biol (Noisy-le-grand) ; 65(6): 56-63, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31472048

RESUMO

The content and integrity of cell-free DNA (cfDNA) before and after surgery in patients with lung cancer were determined to investigate its clinical significance.   Peripheral blood was collected from 120 patients with lung cancer who were treated in our hospital from March 2016 to November 2018, including 50 cases before operation and 70 cases after operation. 60   healthy subjects served as controls. Quantitative PCR was used to determine the cfDNA level of each group. The relationship between cfDNA levels and the clinical features of lung cancer patients was determined. Receiver Operating Curves were used to determine the sensitivity and specificity of cfDNA, CEA, NSE and CYFRA21-1 in lung cancer.  The concentration and integrity of cfDNA before surgery in patients with lung cancer were significantly higher than those after surgery and those in healthy control group. The cfDNA concentration in patients with lung cancer after surgery was significantly higher than that in the control group, but there was no statistical difference in cfDNA integrity between the two groups. There was no significant correlation between cfDNA concentration/integrity and gender, age, tumor type, tumor stage, and expressions of CA199, CA125, and CA153 in patients with lung cancer before or after surgery. However, there were significant correlations between the expression levels of CEA, NSE, and CYFRA21-1 and cfDNA concentration. The expression levels of CEA and CYFRA21-1 were significantly correlated with cfDNA integrity before surgery, while the correlations were not significant after surgery.  The concentration and integrity of cfDNA increased significantly in serum of lung cancer patients. The concentration and integrity of cfDNA in patients with lung cancer after surgery were significantly lower than those before surgery. Thus, cfDNA has high application value in the diagnosis and evaluation of lung cancer.

2.
Abdom Radiol (NY) ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31486869

RESUMO

PURPOSE: To appraise the ability of the computed tomography (CT) radiomics signature for prediction of early recurrence (ER) in patients with hepatocellular carcinoma (HCC). METHODS: A set of 325 HCC patients were enrolled in this retrospective study and the whole dataset was divided into 2 cohorts, including "training set" (225 patients) and "test set" (100 patients). All patients who underwent partial hepatectomy were followed up at least within 1 year. 656 Radiomics features were extracted from arterial-phase and portal venous-phase CT images. Lasso regression model was used for data dimension reduction, feature selection, and radiomics signature building. Univariate analysis was used to identify clinical and radiomics significant features. Models (radiomics signature, clinical model, and combined model) were evaluated by area under the curve (AUC) of receiver operating characteristic curve. The models' performances for prediction of ER were assessed. RESULTS: The radiomics signature was built by 14 selected radiomics features and was significantly associated with ER (P < 0.001); the AUCs of the "train set" and the "test set" were 0.818 (95% CI 0.760-0.865) and 0.719 (95% CI 0.621-0.805), respectively. The tumor size, tumor capsule, and γ-glutamyl transferase (GGT) were significantly associated with ER in the clinical model (P < 0.05). The combined model showed incremental prognostic value, with the AUCs of "training dataset" and "test dataset" were 0.846 (95% CI 0.792-0.890) and 0.737 (95% CI 0.640-0.820), respectively. The radiomics signature, tumor size, and the level of GGT were independent predictors of ER (P < 0.05). CONCLUSIONS: The CT radiomics signature can be conveniently used to predict the ER in patient with HCC. The combined model performed better for prediction of ER than radiomics signature or clinical model.

3.
Aging (Albany NY) ; 112019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31493765

RESUMO

Major depressive disorder (MDD) patients in different age ranges might have different urinary metabolic phenotypes, because age could significantly affect the physiological and psychological status of person. Therefore, it was very important to take age into consideration when studying MDD. Here, a dual platform metabolomic approach was performed to profile urine samples from young and middle-aged MDD patients. In total, 18 and 15 differential metabolites that separately discriminated young and middle-aged MDD patients, respectively, from their respective HC were identified. Only ten metabolites were significantly disturbed in both young and middle-aged MDD patients. Meanwhile, two different biomarker panels for diagnosing young and middle-aged MDD patients, respectively, were identified. Additionally, the TCA cycle was significantly affected in both young and middle-aged MDD patients, but the Glyoxylate and dicarboxylate metabolism and phenylalanine metabolism were only significantly affected in young and middle-aged MDD patients, respectively. Our results would be helpful for developing age-specific diagnostic method for MDD and further investigating the pathogenesis of this disease.

4.
J Synchrotron Radiat ; 26(Pt 5): 1808-1814, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31490173

RESUMO

Transmission X-ray microscopes (TXMs) have become one of the most powerful tools for imaging 3D structures of nano-scale samples using the computed tomography (CT) principle. As a major error source, sample jitter caused by mechanical instability of the rotation stage produces shifted 2D projections, from which reconstructed images contain severe motion artifacts. In this paper, a jitter correction algorithm is proposed, that has high accuracy and computational efficiency for TXM experiments with or without nano-particle markers. Geometric moments (GMs) are measured on segmented projections for each angle and fitted to sinusoidal curves in the angular direction. Sample jitter is estimated from the difference between the measured and the fitted GMs for image correction. On a digital phantom, the proposed method removes jitter errors at different noise levels. Physical experiments on chlorella cells show that the proposed GM method achieves better spatial resolution and higher computational efficiency than the re-projection method, a state-of-the-art algorithm using iterative correction. It even outperforms the approach of manual alignment, the current gold standard, on faithfully maintaining fine structures on the CT images. Our method is practically attractive in that it is computationally efficient and lowers experimental costs in current TXM studies without using expensive nano-particles markers.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31479240

RESUMO

Separators are key safety components for electrochemical energy storage systems. However, the intrinsic poor wettability with electrolyte and low thermal stability of commercial polyolefin separators cannot meet the requirements from the ever-expanding market for high power, high energy and high safety power systems, such as lithium metal, lithium-sulfur and lithium-ion batteries. In this study, scalable bendable networks built with ultra-long silica nanowires (SNs) are developed as stable separators for both high-safety and high-power lithium metal batteries. The three-dimensional porous nature (porosity of 73%) and the polar surface of the obtained SNs separators endues a much better electrolyte wettability, larger electrolyte uptake ratio (325 %), higher electrolyte retention ratio (63 %), and ~ 7 times higher ionic conductivity than that of commercial polypropylene (PP) separators. Moreover, the pore-rich structure of SNs separator can aid to evenly distribute lithium and, in turn, suppress the uncontrollable growth of lithium dendrites to a certain degree. Furthermore, the pure inorganic structure endows the SNs separators with excellent chemical and electrochemical stabilities even at elevated temperatures, as well as excellent thermal stability up to 700 °C. This work underpins the utilization of SNs separators as a rational choice for developing high-performance batteries with metallic lithium anode.

6.
Cell Res ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481760

RESUMO

Breast cancer is a heterogeneous disease. In particular, triple-negative breast cancer (TNBC) comprises various molecular subgroups with unclear identities and currently has few targeted treatment options. Our previous study identified protein C receptor (Procr) as a surface marker on mammary stem cells (MaSCs) located in the basal layer of the normal mammary gland. Given the possible connection of TNBC with basal layer stem cells, we conducted comparative analyses of Procr in breast cancers of mouse and human origin. In mouse mammary tumors, we showed that Procr+ cells are enriched for cancer stem cells (CSCs) in Wnt1 basal-like tumors, but not in Brca1 basal-like tumors or PyVT luminal tumors. In human cancers, PROCR was robustly expressed in half of TNBC cases. Experiments with patient-derived xenografts (PDXs) revealed that PROCR marks CSCs in this discrete subgroup (referred to as PROCR+ TNBC). Interfering with the function of PROCR using an inhibitory nanobody reduced the CSC numbers, arrested tumor growth and prevented rapid tumor recurrence. Our data suggest a key role of MaSC in breast tumorigenesis. Moreover, our work indicates that PROCR can be used as a biomarker to stratify TNBC into clinically relevant subgroups and may provide a novel targeted treatment strategy for this clinically important tumor subtype.

7.
Biomed Pharmacother ; 119: 109429, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31505422

RESUMO

Asthma is a common obstructive airway disease characterized by inflammation and remodeling with a progressive decline in lung function. Fangxiao Formula (FXF) is an herbal medicine that has achieved significant clinical benefits toward asthma patients, but the relevant mechanism has not yet been clarified. The aim of this study was to determine the inhibitory effects of FXF on airway inflammation and remodeling, and investigate the activities of TGF­ß/Smads signaling pathway in the rat asthma model. Rats were sensitized by ovalbumin (OVA) for six weeks to establish the asthma experimental model. OVA-challenged animals were randomly divided into 5 groups and received different concentrations of FXF or dexamethasone. The animals in blank control group received saline only. Lung tissues were collected and analyzed for determining the inflammatory cells infiltration, HE and PAS staining, airway wall thickness and collagen deposition. The productions of inflammatory cytokine productions were analyzed by ELISA in the bronchoalveolar lavage (BAL) fluid. Immunohistochemical analysis was performed to measure the expression of α-SMA and PCNA in lung tissue after the treatment of FXF. The levels of TGF-ß were assessed by both immunohistology and western blotting, and the expression of p-Smad2/3 proteins were determined by western blotting analysis. Our results indicated that FXF attenuated the infiltration of inflammatory cells, decreased the production of Th2 cytokines and simultaneously increased the levels of Th1 cytokine in the asthma rat model. In addition, FXF reduced allergen-induced increased airway wall thickness, goblet cell hyperplasia and collagen deposition. Furthermore, the expression levels of TGF-ß and p-Smad3 were obviously reduced after the treatment of FXF. These results indicate that FXF alleviates airway inflammation and remodeling by restoring the balance of Th1/Th2 cytokines and the TGF-ß/Smad-3 pathway, therefor providing potential therapeutic approach for asthmatic patients.

8.
Pediatr Res ; 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31486778

RESUMO

BACKGROUND: Altered basal ganglia and thalamic connectivity may be critical for cognitive, motor and behavioural impairments common to very preterm (<32 weeks' gestational age) children. This study aims to (1) compare corticostriatal and thalamocortical tract connectivity between very preterm and term-born children at 7 years of age; (2) explore tract connectivity associations with 7-year neurodevelopmental outcomes, and whether these relationships differed between groups. METHODS: Eighty-three very preterm and 19 term-born (≥37 weeks' gestational age) children underwent structural and diffusion magnetic resonance imaging and had a neuropsychological assessment at 7 years. Corticostriatal and thalamocortical tracts were reconstructed and white matter connectivity was estimated with apparent fibre density. RESULTS: Compared with term-born controls, very preterm children had decreased connectivity in tracts linking the caudate to right motor areas (-10%, p = 0.03) and the thalamus with left motor areas (-5.7%, p = 0.03). Reduced connectivity in corticostriatal and thalamocortical tracts was associated with adverse motor functioning in both groups (p = 0.06). Decreased connectivity of the left caudate and putamen with the lateral prefrontal cortex was associated with lower reading performance for controls (p = 0.06). CONCLUSION: Corticostriatal and thalamocortical tracts are vulnerable to very preterm birth. Poorer connectivity in these tracts may underlie the motor impairments observed in very preterm children.

9.
Br J Ophthalmol ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488430

RESUMO

PURPOSE: To assess changes in the position of lamina cribrosa pores (LCPs) induced by acute intraocular pressure (IOP) elevation. METHODS: A prospective observational study. Acute angle-closure suspects who underwent the 2-hour dark room prone provocative test (DRPPT) were included. At baseline and within 5 min after the DRPPT end, tonometry, fundus photography and optical coherence tomography were performed. Optic disc photos taken before and after the DRPPT were aligned and moving distance of each visible LCP was measured (LCPMD). RESULTS: 38 eyes from 27 participants (age: 52.5±10.8 years) were included. The IOP rose from 16.7±3.2 mm Hg at baseline to 23.9±4.3 mm Hg at the DRPPT end. The mean lateral LCPMD was 28.1±14.6 µm (range: 5.0-77.2 µm), which increased with higher IOP rise (p=0.01) and deeper optic cup (p=0.02) in multivariate analysis. The intralamina range and SD of the LCPMD increased with younger age (p=0.01 and p=0.02, respectively) and with wider optic cup (p=0.01 and p=0.02, respectively). The LCP movements were headed to the superior direction in 12 (33%) eyes, inferior direction in 10 (28%) eyes, temporal direction in 9 (25%) eyes, and nasal direction in 5 (14%) eyes. CONCLUSIONS: IOP rise is associated with LCP movements in the frontal plane, which are more pronounced with higher IOP rise and deeper optic cup. The intralamina variability in the IOP rise-associated LCPMD increased with younger age and wider optic cup. IOP variation-associated lateral LCP movements may be of interest to elucidate glaucomatous optic nerve damage.

10.
PLoS One ; 14(9): e0222340, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509580

RESUMO

Growth hormone (GH) is an important hormone released by the pituitary gland that plays a key role in the growth and development of organisms. In our study, TargetScan analysis and the dual luciferase reporter assays were used to predict and screen for miRNAs that might act on the rat Gh1 gene, and we identified miR-543-5p. Then, the GH3 cell line and the primary rat pituitary cells were transfected with miRNA mimic, inhibitor, and siRNA. We detected the Gh1 gene expression and the GH secretion by real-time PCR and ELISAs, respectively, to verify the regulatory effect of miR-543-5p on GH secretion. The results showed that miR-543-5p can inhibit Gh1 mRNA expression and reduce GH secretion. MiR-543-5p inhibitor upregulated Gh1 mRNA expression and increased GH secretion compared with the negative control. In summary, miR-543-5p downregulates Gh1 expression, resulting in a decrease in GH synthesis and secretion, which demonstrates the important role of miRNAs in regulating GH and animal growth and development.

11.
Int J Cancer ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498891

RESUMO

Metastasis is the leading cause of death for non-small cell lung cancer (NSCLC) patients. However, how lung cancer cells invade blood vessels during metastasis remains unclear. Here, based on bioinformatics analyses, we found that PLEK2 might regulate NSCLC migration and vascular invasion. As little is known about the function of PLEK2 in NSCLC, we aimed to clarify this. We demonstrated that PLEK2 was significantly upregulated in TGFß1-treated NSCLC cells through ELK1 transcriptional activation, highly expressed in NSCLC tissues, and negatively correlated with NSCLC overall survival. Meanwhile, PLEK2 overexpression significantly promoted NSCLC epithelial-to-mesenchymal transition (EMT) and migration, HMVEC-L endothelial-to-mesenchymal transition (EndoMT), and the destruction of vascular endothelial barriers. Moreover, PLEK2 knockdown inhibited TGFß1-induced EMT and EndoMT. Furthermore, PLEK2 was found to directly interact with SHIP2 and target it for ubiquitination and degradation in NSCLC cells. Next, we confirmed that SHIP2 overexpression inhibits NSCLC EMT, migration, and invasion and showed that PLEK2 overexpression can activate SHIP2-associated TGF-ß/PI3K/Akt signaling. Our results suggest that PLEK2 could be a novel prognostic marker and potential therapeutic target for NSCLC metastasis and vascular invasion. This article is protected by copyright. All rights reserved.

12.
Virol J ; 16(1): 110, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481132

RESUMO

BACKGROUND: Iridoviruses are large DNA viruses that cause diseases in fish, amphibians and insects. Singapore grouper iridovirus (SGIV) is isolated from cultured grouper and characterized as a ranavirus. ICP46 is defined to be a core gene of the family Iridoviridae and SGIV ICP46 was demonstrated to be an immediate-early (IE) gene associated with cell growth control and could contribute to virus replication in previous research. METHODS: The transcription start site (TSS) and 5'-untranslated region (5'-UTR) of SGIV ICP46 were determined using 5' RACE. The core promoter elements of ICP46s were analyzed by bioinformatics analysis. The core promoter region and the regulation model of SGIV ICP46 promoter were revealed by the construction of serially deleted promoter plasmids, transfections, drug treat and luciferase reporter assays. The identification of virion-associated transcriptional transactivator (VATT) that interact with SGIV ICP46 promoter and their binding site on promoter were performed by electrophoretic mobility shift assays (EMSA), DNA pull-down assays and mass spectrometry (MS). RESULTS: SGIV ICP46 was found to have short 5'-UTR and a presumptive downstream promoter element (DPE), AGACA, which locates at + 36 to + 39 nt downstream of the TSS. The core promoter region of SGIV ICP46 located from - 22 to + 42 nt relative to the TSS. VATTs were involved in the promoter activation of SGIV ICP46 and further identified to be VP12, VP39, VP57 and MCP. A 10-base DNA sequence "ATGGCTTTCG" between the TSS and presumptive DPE was determined to be the binding site of the VATTs. CONCLUSION: Our study showed that four VAATs (VP12, VP39, VP57 and MCP) might bind with the SGIV ICP46 promoter and be involved in the promoter activation. Further, the binding site of the VATTs on promoter was a 10-base DNA sequence between the TSS and presumptive DPE.

13.
J Nat Prod ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503485

RESUMO

Thirteen new labdane-type diterpenoids 1-6, 9-11, 13, 14, 18, and 19 and seven known ones were isolated from the aerial parts of Leonurus japonicus. Compounds 1-5 represent rare examples of labdane-type diterpenoids, of which compounds 1-4 carry an N-chain linked at C-7 in their B-ring and compound 5 featured an α,ß-unsaturated-γ-lactam moiety. The structures and absolute configurations of these new diterpenoids were characterized by a combination of spectroscopic techniques, X-ray crystallography, electronic circular dichroism, and calculated specific rotations. The plant-growth regulatory activity of these compounds on the growth of the roots and shoots of Lactuca sativa and Lolium perenne seedlings were evaluated. Compound 3 showed a broad-spectrum inhibitory activity with the inhibition rates ranging from 60 to 83.5% at a concentration of 200 µg/mL, which were as active as those of glyphosate. Compound 8 had a selective inhibitory activity against the growth of the roots of L. perenne seedlings with an inhibition rate of 81.7%. However, compounds 11 and 16 exhibited significant stimulation effects on the roots of L. sativa with stimulation rates of 59.8 and 65.3%, respectively. In addition, compounds 3 and 8 exhibited inhibitory effects on the germination of L. perenne seeds.

14.
J Nat Prod ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503490

RESUMO

Eight new limonoids, toononoids A-H (1-8), eight new B-seco-29-norlimonoids, toonanoronoids A-H (9-16), and seven known analogues were obtained from the EtOAc extract of the twigs and leaves of Toona ciliata. Compounds 2, 4, 8, and 16 are rare lactam-bearing limonoids. Compounds 1, 14, and 15 possess an unusual γ-methoxybutenolide moiety at C-17, while compounds 9, 10, and 15 have a rare 3ß-hydroxy group. Their 2D structure and relative configurations were identified using spectroscopic data. The absolute configurations of 1, 9, 14, and 15 were established via X-ray diffraction crystallography or comparison of experimental and calculated ECD data. The cytotoxicity of the compounds was assessed toward five human tumor cell lines, and their anti-inflammatory activity was assessed based on NO production using LPS-stimulated RAW264.7 macrophages. Compounds 11 and 12 exerted inhibition toward two tumor cell lines (MCF-7, SW-480) with IC50 values between 2.1 and 3.7 µM, while 18-22 inhibited the proliferation of HL-60, MCF-7, and SW-480 cells (IC50 0.6-4.0 µM). Only compound 4 exhibited weak anti-inflammatory activity with an IC50 value of 28.3 µM.

15.
Int J Mol Sci ; 20(18)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505747

RESUMO

Mycoplasma hyopneumoniae (Mhp) and porcine circovirus type 2 (PCV2) are the main pathogens for mycoplasmal pneumonia of swine (MPS) and post-weaning multisystemic wasting syndrome (PMWS), respectively. Infection by these pathogens often happens together and causes great economic losses. In this study, a kind of recombinant baculovirus that can display P97R1P46P42 chimeric protein of Mhp and the capsid (Cap) protein of PCV2 was developed, and the protein location was identified. Another recombinant baculovirus was constructed without tag proteins (EGFP, mCherry) and was used to evaluate the immune effect in experiments with BALB/c mice and domestic piglets. Antigen proteins P97R1P46P42 and Cap were expressed successfully; both were anchored on the plasma membrane of cells and the viral envelope. It should be emphasized that in piglet immunization, the recombinant baculovirus vaccine achieved similar immunological effects as the mixed commercial vaccine. Both the piglet and mouse experiments showed that the recombinant baculovirus was able to induce humoral and cellular responses effectively. The results of this study indicate that this recombinant baculovirus is a potential candidate for the further development of more effective combined genetic engineering vaccines against MPS and PMWS. This experiment also provides ideas for vaccine development for other concomitant diseases using the baculovirus expression system.

16.
Plant Cell Rep ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501956

RESUMO

KEY MESSAGE: Banana MaBZR1/2 interact with MaMPK14 to enhance the transcriptional inhibition of cell wall modifying genes including MaEXP2, MaPL2 and MaXET5. Fruit ripening and softening, the major attributes to perishability in fleshy fruits, are modulated by various plant hormones and gene expression. Banana MaBZR1/2, the central transcription factors of brassinosteroid (BR) signaling, mediate fruit ripening through regulation of ethylene biosynthesis, but their possible roles in fruit softening as well as the underlying mechanisms remain to be determined. In this work, we found that MaBZR1/2 directly bound to and repressed the promoters of several cell wall modifying genes such as MaEXP2, MaPL2 and MaXET5, whose transcripts were elevated concomitant with fruit ripening. Moreover, yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays indicated that MaBZR1/2 physically interacted with a mitogen-activated protein kinase MaMPK14, and this interaction strengthened the MaBZR1/2-mediated transcriptional inhibitory abilities. Collectively, our study provides insight into the mechanism of MaBZR1/2 contributing to fruit ripening and softening, which may have potential for banana molecular improvement.

17.
Cell Prolif ; : e12689, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31502302

RESUMO

OBJECTIVES: Osteogenesis is coupled with angiogenesis during bone remodelling. G-protein-coupled receptor (GPCR) kinase 2-interacting protein-1 (GIT1) is an important protein that participates in fracture healing by regulating angiogenesis. This study investigated whether GIT1 could affect bone mesenchymal stem cells (BMSCs) to secrete angiogenic factors to enhance fracture healing by promoting angiogenesis and its possible mechanism. MATERIALS AND METHODS: The angiogenesis of mice post-fracture was detected by micro-CT and immunofluorescence. Subsequently, vascular endothelial growth factor (VEGF) level in mouse and human BMSCs (hBMSCs) under TNF-α stimulation was detected. The hBMSCs were transfected with GIT1 shRNAs to further explore the relationship between GIT1 and VEGF and angiogenesis in vitro. Furthermore, based on previous research on GIT1, possible signal pathways were investigated. RESULTS: GIT1 knockout mice exhibited impaired angiogenesis and delayed fracture healing. And GIT1 deficiency remarkably reduced the expression of VEGF mRNA in BMSCs, which affected the proliferation and migration of human umbilical vein endothelial cells. GIT1 knockdown inhibited the activation of Notch and NF-κB signals by decreasing nuclear transportation of NICD and P65/P50, respectively. Overexpression of the canonical NF-κB subunits P65 and P50 markedly increased NICD-dependent activation of recombination signal-binding protein-jκ reporter. Finally, GIT1 enhanced the affinity of NF-κB essential modulator (NEMO) for K63-linked ubiquitin chains via interaction with NEMO coiled-coil 2 domains. CONCLUSION: These data revealed a positive role for GIT1 by modulating the Notch/NF-κB signals which promoting paracrine of BMSCs to enhance angiogenesis and fracture healing.

18.
Exp Eye Res ; : 107792, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31499034

RESUMO

Oxidative stress and subsequent chronic inflammation result in dysfunction of the retinal pigment epithelium (RPE) and represent therapeutic targets in the context of age-related macular degeneration (AMD). However, molecular mechanisms that linked oxidative stress and inflammation still unclear. As an important byproduct of oxidative stress, 4-hydroxynonenal (4-HNE) induces apoptosis and lysosome dysregulation of RPE cells. In the present study, we evaluated cytokines production of RPE cells induced by 4-HNE by using cytokine array and confirmed that 4-HNE induced IL-6, IL-1ß and TNF-α production in a concentration dependent manner. Specifically, 4-HNE also induced IL-10 and TGF-ß production in low concentration. Molecular analysis revealed that intracellular HSP70 inhibited 4-HNE-induced production of pro-inflammatory cytokines, and 4-HNE exerted proinflammatory effects in RPE cells by enhancing extracellular release of HSP70, as efflux inhibitor Methyl-ß-cyclodextrin (MBC) treatment significantly blocked the release of HSP70 and decreased IL-6 production of RPE cells induced by 4-HNE. Meanwhile, HSP70 inducer arimoclomol increased intracellular HSP70 production, but showed no influence on its extracellular level, also performed anti-inflammatory effects in 4-HNE-stimulated RPE cells. Whereas the anti-inflammatory effects of paeoniflorin, an HSP70 inducer simultaneously promoted its extracellular efflux, was lower than arimoclomol. In addition, we further confirmed that MBC exhibited synergetic effect with both paeoniflorin and arimoclomol to inhibit the production of proinflammatory cytokines induced by 4-HNE. Taken together, these results indicate that HSP70 plays a vital role in regulating inflammation of RPE cells induced by oxidative stress and might be a potential novel target for clinical treatment of AMD.

19.
Sensors (Basel) ; 19(18)2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31500306

RESUMO

This paper presents a temperature-insensitive resonant pressure sensor, which is mainly composed of a silicon-on-insulator (SOI) wafer for pressure measurements and a silicon-on-glass (SOG) cap for vacuum packaging. The variations of pressure under measurement bend the pressure sensitive diaphragm and regulate the intrinsic frequencies of the resonators in the device layer. While, variations of temperature cannot significantly change the intrinsic frequencies of the resonators, due to the SOG cap to offset generated thermal stress. Numerical simulations, based on finite element analysis, were conducted to calculate the residual thermal stress and optimize the sensing structures. Experimental results show that the Q-factors of the resonators are higher than 16,000, with a differential pressure sensitivity of 11.89 Hz/kPa, a nonlinearity of 0.01% F.S and a low fitting error of 0.01% F.S with the pressure varying from 100 kPa to 1000 kPa. In particular, a temperature sensitivity of ~1 Hz/°C was obtained in the range of -45 °C to 65 °C, which is one order of magnitude lower than the previously reported counterparts.

20.
Nat Med ; 25(9): 1428-1441, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31501614

RESUMO

Psychological distress has long been suspected to influence cancer incidence and mortality. It remains largely unknown whether and how stress affects the efficacy of anticancer therapies. We observed that social defeat caused anxiety-like behaviors in mice and dampened therapeutic responses against carcinogen-induced neoplasias and transplantable tumors. Stress elevated plasma corticosterone and upregulated the expression of glucocorticoid-inducible factor Tsc22d3, which blocked type I interferon (IFN) responses in dendritic cell (DC) and IFN-γ+ T cell activation. Similarly, close correlations were discovered among plasma cortisol levels, TSC22D3 expression in circulating leukocytes and negative mood in patients with cancer. In murine models, exogenous glucocorticoid injection, or enforced expression of Tsc22d3 in DC was sufficient to abolish therapeutic control of tumors. Administration of a glucocorticoid receptor antagonist or DC-specific Tsc22d3 deletion reversed the negative impact of stress or glucocorticoid supplementation on therapeutic outcomes. Altogether, these results indicate that stress-induced glucocorticoid surge and Tsc22d3 upregulation can subvert therapy-induced anticancer immunosurveillance.

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