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Postoperative cognitive dysfunction (POCD) impacts a significant number of patients annually, frequently impairing their cognitive abilities and resulting in unfavorable clinical outcomes. Aimed at addressing cognitive impairment, vagus nerve stimulation (VNS) is a therapeutic approach, which was used in many mental disordered diseases, through the modulation of vagus nerve activity. In POCD model, the enhancement of cognition function provided by VNS was shown, demonstrating VNS effect on cognition in POCD. In the present study, we primarily concentrates on elucidating the role of the VNS improving the cognitive function in POCD, via two potential mechanisms: the inflammatory microenvironment and epigenetics. This study provided a theoretical support for the feasibility that VNS can be a potential method to enhance cognition function in POCD.
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Introducing a core hole significantly alters the electronic structure of a molecule, and various X-ray spectroscopy techniques are available for probing the valence electronic structure in the presence of a core hole. In this study, we visually demonstrate the influence of a core hole on valence excitations by computing the ultraviolet absorption spectra and the shake-up satellites in X-ray photoelectron spectra for pyrrole, furan, and thiophene, as complemented by the natural transition orbital (NTO) analysis over transitions with and without a core hole. Employing equivalent core hole time-dependent density functional theory (ECH-TDDFT) and TDDFT methods, we achieved balanced accuracy in both spectra for reliable comparative analysis. We tracked the same involved valence transition in both spectra, offering a vivid illustration of the core hole effect via the change in corresponding particle NTOs introduced by a 1s core hole on a Cα, Cß, or O atom. Our analysis deepens the understanding of the core hole effect on valence transitions, a phenomenon ubiquitously observed in general X-ray spectroscopic analyses.
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Understanding proton transfer (PT) dynamics in condensed phases is crucial in chemistry. We computed a 2D map of N 1s X-ray photoelectron/absorption spectroscopy (XPS/XAS) for an organic donor-acceptor salt crystal against two varying N-H distances to track proton motions. Our results provide a continuous spectroscopic mapping of O-H···NâO-··· H+-N processes via hydrogen bonds at both nitrogens, demonstrating the sensitivity of N 1s transient XPS/XAS to hydrogen positions and PT. By reducing the O-H length at N1 by only 0.2 Å, we achieved excellent theory-experiment agreement in both XPS and XAS. Our study highlights the challenge in refining proton positions in experimental crystal structures by periodic geometry optimizations and proposes an alternative scaled snapshot protocol as a more effective approach. This work provides valuable insights into X-ray spectra for correlated PT dynamics in complex crystals, benefiting future experimental studies.
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INTRODUCTION: Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of male C57BL/6 mice and reveal the potential underlying mechanisms. METHODS: A total of 60 male C57BL/6 mice were randomly divided into four groups. They were exposed to fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/mL of nicotine, and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. RESULTS: Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: The findings of the present study indicate that the safety of E-cig should be further evaluated. IMPLICATIONS: Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.
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Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Camundongos , Animais , Masculino , Humanos , Nicotina/efeitos adversos , Nicotina/metabolismo , Camundongos Endogâmicos C57BL , Pulmão , Aerossóis/farmacologiaRESUMO
Cu-O2 structures play important roles in bioinorganic chemistry and enzyme catalysis, where the bonding between the Cu and O2 parts serves as a fundamental research concern. Here, we performed a multiconfigurational study on the copper L2,3-edge X-ray absorption spectra (XAS) of two copper enzyme model complexes to gain a better understanding of the antibonding nature from the clearly interpreted structure-spectroscopy relation. We obtained spectra in good agreement with the experiments by using the restricted active space second-order perturbation theory (RASPT2) method, which facilitated reliable chemical analysis. Spectral feature interpretations were supported by computing the spin-orbit natural transition orbitals. All major features were assigned to be mainly from Cu 2p to antibonding orbitals between Cu 3d and O2 π*, Cu 3d-πO-O* (type A), and a few also to mixed antibonding/bonding orbitals between Cu 3d and O2 π, Cu 3d ± πO-O (type M). Our calculations provided a clear illustration of the interactions between Cu 3d and O2 π*/π orbitals that are carried in the metal L-edge XAS.
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Purpose: Hydrogels containing the nano-self-assembling peptide RADA16-I (Nanogels) were utilized as scaffolds to establish airway organoids and an adenovirus-infected model. The results support in vitro adenovirus studies, including isolation and culture, pathogenesis research, and antiviral drug screening. Methods: HSAEC1-KT, HuLEC-5a and HELF cells were cocultured in RADA16-I hydrogel scaffolds to construct an airway organoid model. Adenovirus was used to infect this model for adenovirus-related studies. The morphological characteristics and the proliferation and activity of airway organoids before and after adenovirus infection were evaluated. The expression of the airway organoid marker proteins CC10, KRT8, AQP5, SPC, VIM and CD31 was detected. TEM and qPCR were used to detect adenovirus proliferation in airway organoids. Results: HSAEC1-KT, HuLEC-5a and HELF cells cocultured at 10:7:2 self-assembled into airway organoids and maintained long-term proliferation in a RADA16-I hydrogel 3D culture system. The organoids stably expressed the lumen-forming protein KRT8 and the terminal airway markers AQP5 and SPC. Adenoviruses maintained long-term proliferation in this model. Conclusion: An airway-organoid model of adenovirus infection was constructed in vitro from three human lung-derived cell lines on RADA16-I hydrogels. The model has potential as a novel research tool for adenovirus isolation and culture, pathogenesis research, and antiviral drug screening.
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Infecções por Adenoviridae , Peptídeos , Humanos , Peptídeos/farmacologia , Adenoviridae/genética , Organoides , Antivirais , HidrogéisRESUMO
Truncated cluster models represent an effective way for simulating x-ray spectra of 2D materials. Here, we systematically assessed the influence of two key parameters, the cluster shape (honeycomb, rectangle, or parallelogram) and size, in x-ray photoelectron (XPS) and absorption (XAS) spectra simulations of three 2D materials at five K-edges (graphene, C 1s; C3N, C/N 1s; h-BN, B/N 1s) to pursue the accuracy limit of binding energy (BE) and spectral profile predictions. Several recent XPS experiments reported BEs with differences spanning 0.3, 1.5, 0.7, 0.3, and 0.3 eV, respectively. Our calculations favor the honeycomb model for stable accuracy and fast size convergence, and a honeycomb with â¼10 nm side length (120 atoms) is enough to predict accurate 1s BEs for all 2D sheets. Compared to all these experiments, predicted BEs show absolute deviations as follows: 0.4-0.7, 0.0-1.0, 0.4-1.1, 0.6-0.9, and 0.1-0.4 eV. A mean absolute deviation of 0.3 eV was achieved if we compare only to the closest experiment. We found that the sensitivity of computed BEs to different model shapes depends on systems: graphene, sensitive; C3N, weak; and h-BN, very weak. This can be attributed to their more or less delocalized π electrons in this series. For this reason, a larger cluster size is required for graphene than the other two to reproduce fine structures in XAS. The general profile of XAS shows weak dependence on model shape. Our calculations provide optimal parameters and accuracy estimations that are useful for x-ray spectral simulations of general graphene-like 2D materials.
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Polynitrogen molecules and ions are important building blocks of high energy density compounds (HEDCs). High energy bonds formed at the N sites can be effectively probed by X-ray photoelectron spectroscopy (XPS) at the N K-edge. In this work, with the density functional theory and the ΔKohn-Sham scheme, we simulated the N1s ionic potentials (IPs) of 72 common polynitrogen molecules [tetrazoles, pentazole (N5H), diazines, triazines, tetrazines, furazans, oxazoles and oxadiazoles], ions [pentazolate anion (cyclo-N5-), pentazenium cation (N5+), etc.], and molecular (NH3â¯N5H, H2Oâ¯N5H) and ionic (NH4+â¯N5-, H3O+â¯N5-) pairs, as well as mononitrogen relatives. These constitute a small theoretical database for absolute N1s IPs with an average accuracy of ca. 0.3 eV. To understand the structure-IP relationship within this family, effects of side substituent and bridging groups, local bonding types (amine or imine N), charge and protonation states, and vibronic coupling were analyzed based on selected systems. This study in the gas phase collects inherent chemical shifts of nitrogen in high-energy NN and NC bonds, which provides an essential reference into XPS interpretations of more complex HEDCs in the solid state. We especially highlight the evident N1s chemical shifts induced by protonation for nitrogen in the five-membered ring (N5H versus cyclo-N5-, ca. 7 eV; NH3â¯N5H versus NH4+â¯N5-, ca. 3 eV; H2Oâ¯N5H versus H3O+â¯N5-, ca. 2 eV), and suggest XPS as a sensitive tool in determining the hydrogen positions in pentanitrogen-based HEDCs.
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The purpose of this study was to explore conventional, diffusion, and dynamic contrast-enhanced MRI (DCE-MRI) characteristics for differentiating metaplastic Warthin's tumor (MWT) from other tumor types of the parotid gland, including non-metaplastic Warthin's tumor (non-MWT), pleomorphic adenoma (PA), and malignant tumor (MT). A total of 178 patients with histologically proven tumors of the parotid gland, including 21 MWTs, 49 non-MWTs, 66 PAs, and 42 MTs, were enrolled in the study. Conventional MRI was performed in all patients. One hundred and fifty patients had preoperative diffusion-weighted MR imaging (DWI), and 62 patients had preoperative DCE-MRI. The differences in the conventional, DCE-MRI, and DWI records between MWTs and the other three tumor types were statistically evaluated. Compared with non-MWTs and PAs, there was a statistically significant difference in circumscription (p < 0.01). The ill-defined circumscription was more common in MWTs than non-MWTs and PAs. Compared with PAs, there was a statistically significant difference in morphology (p < 0.05). The lobulated morphology was more common in PAs than MWTs. Compared with PAs and MTs, there was a statistically significant difference in the T2 signal of the solid component (p < 0.01). The T2 moderate intensity of solid components was more common in MWTs than PAs and MTs. The solid components of PAs mostly showed hyperintense on T2-weighted imaging. Cyst/necrosis was more common in MWTs than PAs and MTs. Hyperintense of cyst/necrosis was more common in MWTs and non-MWTs. With respect to contrast enhancement, 52.4% MWTs exhibited moderate or marked enhancement, and most non-MWTs (81.6%) exhibited mild enhancement. Most PAs (84.8%) exhibited marked enhancement. The mean ADC value of MWTs (0.94 × 10-3 ± 0.11 mm2/s) was signiï¬cantly lower than that of the PAs (1.60 × 10-3 ± 0.17 mm2/s) (p < 0.001). On DCE-MRI, six of eight MWTs demonstrated TIC of type B. Although MWT is rare, conventional MRI characteristics, DWI and DCE-MRI can provide useful information for differentiating MWT from other parotid mass.
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Adenolinfoma , Cistos , Neuroblastoma , Neoplasias Parotídeas , Adenolinfoma/diagnóstico por imagem , Adenolinfoma/patologia , Cistos/patologia , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética/métodos , Metaplasia/patologia , Necrose/patologia , Neuroblastoma/patologia , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/patologia , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Hepatoma upregulated protein (HURP) and Ki-67 have been identified as cancer-related genes involved in cell growth and proliferation. Previous experimental studies have suggested an essential role for HURP expression in liver carcinogenesis. However, data regarding HURP expression in hepatocellular carcinoma (HCC) and its correlation with patient outcomes are limited. In this study, we examined the clinicopathologic features associated with HURP expression in HCC, and compared them to the results of the Ki-67 study. METHODS: Eighty-seven resected HCC at tumor, node, metastasis (TNM) stages I (n = 28), II (n = 29), and III (n = 30) were evaluated. HURP and Ki-67 expression were assessed by immunohistochemistry. Multivariate analysis was used to examine the prognostic significance of HURP and Ki-67 expression. RESULTS: HURP expression in HCC tissue was observed in 59% of patients and associated with female sex, low white blood cell count, and low platelet count. Ki-67 expression was observed in 67% of patients and associated with younger age, higher serum α-fetoprotein (AFP) levels, and frequent microvascular invasion. Univariate analysis showed that factors related to overall survival were: age >55 years, AFP >20 ng/mL, indocyanine green retention rate at 15 minutes (ICG-15) >15%, tumor size >5 cm, multiple tumors, macrovascular invasion, microvascular invasion, Ki-67 expression, and serum vascular endothelial growth factor >170 pg/mL. HURP expression was not associated with postresection survival. Multivariate analysis indicated that macrovascular invasion, multiple tumors, ICG-15 >15%, and Ki-67 expression were independent factors for overall survival. Multiple tumors and Ki-67 expression were independent factors related to recurrence-free survival. CONCLUSION: In our study, HURP expression in HCC tissue was not associated with post-resection survival. Ki-67 expression was an independent prognostic factor for survival. Our results suggest that the effect of HURP activity on growth, invasion, and postresection outcome of HCC in actual patients is less than previously demonstrated in experimental studies.
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Carcinoma Hepatocelular/patologia , Antígeno Ki-67/análise , Proteínas de Neoplasias/análise , Proliferação de Células , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Antígeno Ki-67/genética , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Prognóstico , Estudos Prospectivos , Análise de SobrevidaRESUMO
Background: Several previous reports of anaplastic ependymomas have described their imaging features, and most of these studies were case reports. However, no studies have compared the magnetic resonance imaging (MRI) features between the infratentorial and supratentorial anaplastic ependymomas. Objective: The goal of this study was to explore MRI characteristics for intracranial anaplastic ependymomas. Material and Methods: We retrospectively reviewed the demographics of 165 patients and MRI findings of 60 patients with supratentorial (SAEs) and infratentorial anaplastic ependymomas (IAEs) before surgery. The demographics and MRI features for SAEs and IAEs were compared and evaluated. Results: Among the 60 patients, most SAEs (91.7%) were extraventricular, whereas most IAEs (91.7%) were intraventricular. Of sixty intracranial anaplastic ependymomas, most lesions were well-defined (n = 45) and round-like (n = 36). On T1-weighted imaging, compared with the gray matter, the SAEs exhibited heterogeneous signal intensity, whereas IAEs exhibited iso-hypointense signals. T2 signals exhibited greater associations with hyperintense signals in IAEs; however, SAEs showed hyperintense or hypointense-hyperintense. On diffusion-weighted imaging (DWI), almost all solid tissues of SAEs appeared as hyperintense, whereas IAEs exhibited iso-hypointense signals. Peritumoral edema and intratumoral hemorrhage occurred more frequently in SAEs. Almost all anaplastic ependymomas exhibited heterogeneous enhancement. Cysts or necrosis was associated with 56 anaplastic ependymomas; however, large cysts were more prevalent in SAEs. On magnetic resonance spectroscopy (MRS), the mean choline/creatine (Cho/Cr) and choline/N-acetyl-aspartate (Cho/NAA) ratio of anaplastic ependymomas were (6.58 ± 4.26) and (8.84 ± 6.34), respectively, representing typical high-grade tumors. Conclusion: We demonstrate the conventional and functional MRI features of intracranial anaplastic ependymomas, including DWI and MRS. MRI characteristics, such as location, cyst, diffusion restriction, and peritumoral edema, differed between supratentorial and infratentorial locations. Cho/Cr and Cho/ NAA ratios of anaplastic ependymomas are increased.
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OBJECTIVE: To investigate the effects of enterovirus 71 (EV71) on mitochondrial dynamics in human Glioma U251 cells. METHODS: The EV71 was replicated in Vero cells and the 50% tissue culture infective dose (TCID 50) was calculated based on the Reed-Muench formula. After the U251 cells were infected with EV71, the cellular morphology was assessed through the light microscope. The mitochondrial morphology was detected by MitoTracker Deep Red staining under laser confocal microscopy and the mitochondrial ultrastructure was visualized by transmission electron microscopy. The expressions of mitochondrial fission proteins Drp1, p-Drp1 and fusion protein Opa1 were examined by Western blot. The level of ATP was measured by a commercial ATP assay kit. The generation of mitochondrial superoxide was detected by MitoSOX staining. RESULTS: The TCID 50 of EV71 was 10 ï¼5.4/0.1 mL. Twenty-four or 48 h after EV71 infection, the U251 cells appeared shrunken, round and dead. The laser confocal microscopy and transmission electron microscopy images showed that the EV71 infection induced mitochondrial elongation and cristae damage. Moreover, Western blot analysis demonstrated that the protein expressions of Drp1 and Opa1 were downregulated at both 24 and 48 h after EV71 infection in U251 cells, companied with a significant increase in Drp1 phosphorylation at 48 h after infection ( P<0.05). In addition, a decreased ATP level and elevated mitochondrial superoxide generation were observed in the EV71 infected group, as compared to the control group. CONCLUSION: Our study demonstrated that infection with EV71 led to changes of mitochondrial morphology and dynamics in U251 cells, which may impair mitochondrial function and contribute to nervous system dysfunction.
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Neoplasias Encefálicas/virologia , Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Glioma/virologia , Dinâmica Mitocondrial , Animais , Chlorocebus aethiops , Enterovirus Humano A/patogenicidade , Infecções por Enterovirus/complicações , Humanos , Sistema Nervoso/fisiopatologia , Sistema Nervoso/virologia , Células Tumorais Cultivadas , Células VeroRESUMO
While the effect of increasing tidewater inundation caused by sea-level rise on carbon cycling had been well studied in saltmarshes, little is known about the effect of increasing tidewater inundation on CO2 and CH4 effluxes in the tidal freshwater marsh soils. Herein, the effects of tide inundation on porewater geochemistries (NH4+, NO3-, DOC, dissolved CH4, and DIC) and CH4 and CO2 effluxes were examined in the soils of tidal freshwater marshes in the Minjiang River Estuary, East China Sea. By applying "mesocosm" and a simulated tide pool, the tide inundation height increased by 15 cm and 30 cm over the control (CK). The CO2 effluxes decreased by 28.53% and 36.56%, and the dissolved CH4 concentrations increased by 47.83% and 73.91%, in treatments (CK+15 cm) and (CK+30 cm), respectively. The CH4 effluxes did not change significantly in the treatment (CK+15 cm), but increased by 29.27% in treatment (CK+30 cm). The increasing tidewater inundation had no significant impact on DOC concentrations, but increased NH4+ concentrations and decreased DIC and NO3- concentrations. Increasing tide inundation also reduced the temperature sensitivity of CH4 and CO2 effluxes. The study highlighted that the sea level rise-induced increase in tidewater inundation would decrease the annual global warming potential of tidal freshwater wetlands by 28% and 35% in the next 50 and 100 years, respectively.
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We performed a density functional theory (DFT) study on X-ray photoelectron (XPS) and absorption (XAS) spectra of graphitic carbon nitride (g-C3N4) nanosheets at the N and C K-edges. A combined cluster-periodic approach was employed to calculate XPS spectra, in which the core ionic potential (IP) of the solid 2D material was computed by subtracting the work function (obtained with periodic conditions) from the gas phase IP (obtained with large cluster models). With amino-terminated supermolecules of different sizes, we obtained convergent spectra and provide new assignments for 5 nitrogen [1 sp2; 4 sp3 (bridging, tertiary, and primary/secondary amino nitrogens)] and 4 carbon (all bonded with three nitrogens) local structures. A good agreement with experiments was obtained, with the N1s (C1s) main peak position differing by 0.1-0.2 eV (0.5-0.8 eV). Our simulations show that N1s XPS of pure g-C3N4 contains only two major features at 398.6 and 401.2 eV, contributed from sp2-N and sp3-N, respectively. The chemical shifts of all sp3-N are so close (deviating by 0.3-0.6 eV) that terminal amino groups -NHx (x = 1, 2) will only be distinguished in high-resolution measurements. In C1s XPS, all carbons show similar (deviation < 0.2 eV) IPs, as determined by the same nearest neighbors. We further excluded the effect of shake-up satellites that may change our XPS interpretations by equivalent core hole time-dependent DFT (ECH-TDDFT) simulations. The effect of vibronic coupling is small (redistribution is only 0.1-0.3 eV to the higher-energy region) in the N1s edge as estimated from the asymmetric main peak shape, and negligible in the C1s edge. Quicker size convergence was found in XAS than XPS. In N1s XAS, we identified a weak π* spectral feature at 400-401 eV for both -NHx and tertiary nitrogens. Our study provides a clear theoretical reference for X-ray spectral fingerprints of different local structures, which is useful for analysis of g-C3N4 based materials with various designed or unavoidable structural modifications. We also highlight our combined cluster-periodic approach in calculating the K-edge XPS spectra of general 2D materials which predicts accurate absolute values.
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Previous studies have revealed that exosomes influence tumour metastasis, diagnosis and treatment. In addition, exosomal microRNAs (miRNAs/miRs) are closely associated with the metastatic microenvironment; however, the regulatory role of exosomal miRNAs from prostate cancer cells on bone metastasis remains poorly understood. In the present study, a series of experiments were performed to determine whether exosomal miR-375 from LNCaP cells promote osteoblast activity. Exosomes were isolated and purified by ultracentrifugation, total RNA from cells and total miRNA from exosomes were then extracted, and miR-375 levels were detected by reverse transcription-quantitative polymerase chain reaction. Exosome libraries from LNCaP and RWPE-1 cells were sequenced and selected using an Illumina HiSeq™ 2500 system. The effects of exosomes on osteoblasts were determined and osteoblast activity was evaluated by measuring the activity of alkaline phosphatase, the extent of extracellular matrix mineralisation and the expression of osteoblast activity-associated marker genes. Morphological observations, particle size analysis and molecular phenotyping confirmed that cell supernatants contained exosomes. Differential expression analysis confirmed high miR-375 expression levels in LNCaP cell-derived exosomes. The ability of exosomes to enter osteoblasts and increase their levels of miR-375 was further analysed. The results demonstrated that exosomal miR-375 significantly promoted osteoblast activity. In conclusion, the present study may lead to further investigation of the function role of exosomal miR-375 in the activation and differentiation of osteoblasts in PCa.
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BACKGROUND: Neuropilins (Nrps) are a new type of broad-spectrum tumor marker. Currently, a method for accurate simultaneous quantification of Nrps is not available. We aimed to develop a bead-based and duplexed flow cytometric assay that could be used for accurate and simultaneous quantification of Nrp1 and Nrp2 for scientific research or clinical diagnosis. METHODS: We coupled anti-human Nrp1-11# mAb and anti-human Nrp2-C3 mAb to magnetic beads 18# and 25#, respectively. Capturing antibodies and detecting antibodies were then combined to detect Nrps by a bead-based Luminex assay, which was subsequently applied to quantify Nrps in clinical serum samples. RESULTS: The results showed that the detection value of Nrps ranged from 10 to 100 000 pg/mL for Nrp1 and from 25 to 100 000 pg/mL for Nrp2. The detection sensitivity reached 10 pg/mL for Nrp1 and 24.8 pg/mL for Nrp2. Intra-assay variances ranged from 1.0% to 2.6% for Nrp1 and from 2.9% to 4.0% for Nrp2, and interassay variances ranged from 1.5% to 6.4% for Nrp1 and from 4.2% to 8.1% for Nrp2. The Nrp1 and Nrp2 recoveries were 96.6%-103.6% and 95.6%-102.3%, respectively. Irrelevant antigens had no interference in the paired-detection system, and the mean fluorescence intensity (MFI) values were stable for months. CONCLUSION: A bead-based, duplexed flow cytometric assay (xMAP® technology) was developed to detect Nrp1 and Nrp2. The assay provided rapid, high-throughput results and was much more sensitive, specific, reproducible, and stable than existing assays. In addition, this assay could be applied in early-stage cancer screening, tumor malignancy analysis, and prognosis assessment.
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Imunoensaio/métodos , Neuropilina-1/sangue , Neuropilina-2/sangue , Anticorpos Monoclonais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Biotinilação , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoensaio/instrumentação , Neoplasias/sangue , Neuropilina-1/imunologia , Neuropilina-2/imunologia , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
In this paper, the six C32 isomers which were of crucial importance in the manufacture of new electronic components were identified by X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS). For the discernment, geometry optimizations of the six isomers have been carried out, and the C1s XPS and NEXAFS spectra have been simulated in the frame of density functional theory (DFT). XPS spectra, as accurately reflection of different chemical environments where a particular element was located, provided an effective way to identify the six isomers of C32. The NEXAFS spectra, which were commonly used in the electronic structure detection, captured information of unoccupied orbital and showed many recognizable characteristics. To further investigate the source of spectral features, the spectral components calculated from different types of carbon atoms in each C32 isomer also have been well explored and discussed.
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AIMS: C-reactive protein (CRP) and matrix metalloproteinase (MMP)-9 are involved in the inflammation of atherosclerosis lesions. Genistein (Gen) has been demonstrated to exert beneficial effect on the cardiovascular system. However, it remains unclear whether Gen produces anti-inflammatory effect in vascular smooth muscle cells (VSMCs). Therefore, we investigated the effects of Gen on CRP and MMP-9 expressions induced by angiotensin (Ang) II in VSMCs and the related molecular mechanism. MAIN METHODS: Rat VSMCs were cultured, and Ang II was used as a stimulant for CRP and MMP-9 expressions. CRP level was measured by ELISA. The mRNA and protein expressions of related indexes were identified by reverse transcription-polymerase chain reaction and western blot, respectively. KEY FINDINGS: Gen inhibited Ang II-stimulated CRP and MMP-9 mRNA and protein expressions in concentration- and time-dependent manners. Additionally, Gen ameliorated Ang II-induced p-ERK1/2, p-p38 and NF-κB expressions, antagonized Ang II-downregulated peroxisome proliferation-activated receptor (PPAR) γ and estrogen receptor (ER) ß expressions. After treating the VSMCs with GW9662 or ICI182780 in Gen treated groups, inhibitory effect of Gen on CRP and MMP-9 expressions were antagonized in Ang II-stimulated VSMCs. The treatment of VSMCs with ICI182780 abolished downregulations of p-p38/p-ERK1/2, and antagonized upregulation of PPARγ by Gen in Ang II-stimulated VSMCs. Moreover, the inhibitory effect of Gen on Ang II-stimulated NF-κB expression was abolished after preincubation of VSMCs with GW9662 in Gen treated groups. SIGNIFICANCE: Gen exerts anti-inflammatory property via the ER-p38/ERK1/2-PPARγ-NF-κB-CRP/MMP-9 signal pathway in Ang II-stimulated VSMCs.
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Anti-Inflamatórios/farmacologia , Proteína C-Reativa/metabolismo , Genisteína/farmacologia , Inflamação/tratamento farmacológico , Miócitos de Músculo Liso/efeitos dos fármacos , Angiotensina II/administração & dosagem , Animais , Anti-Inflamatórios/administração & dosagem , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Células Cultivadas , Relação Dose-Resposta a Droga , Genisteína/administração & dosagem , Inflamação/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , NF-kappa B/metabolismo , PPAR gama/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
BACKGROUND: Several studies have shown that B7-H4 expression is significantly increased in ovarian cancer. However, the role of B7-H4 expression in ovarian cancer remains unclear, and some studies reporting conflicting results. A systematic review of the literature and meta-analysis were conducted to assess the clinicopathologic characteristics and prognostic significance of B7-H4 in ovarian cancer. METHODS: Eligible studies were searched in the PubMed, MEDLINE, Cochrane Library, and the China National Knowledge Infrastructure databases. The included studies assessed the relationship between B7-H4 expression and clinicopathologic features or prognosis in patients with ovarian cancer through September 2017. A total of 1045 patients in 10 studies were included in the meta-analysis. Stata software version 12.0 was used to analyze the data. We used an odds ratio (OR) or hazard ratio (HR) with a 95% confidence interval (CI) to assess the risk or hazard association. RESULTS: B7-H4 expression in ovarian cancer patients was significantly increased (OR: 4.20, 95% CI: 2.85-6.18, Zâ=â6.91, Pâ<â.05), and heterogeneity was low between studies (Iâ=â8.2%, Pâ=â.366). With respect to the clinicopathologic features, no relation was detected between B7-H4 expression and International Federation of Gynaecology and Obstetricsstages stages (OR: 0.81, 95% CI: 0.64-1.03, Zâ=â1.70, Pâ=â.09), pathologic grade (OR: 0.91, 95% CI: 0.72-1.16, Zâ=â0.76, Pâ=â.45), tumor metastasis (OR: 1.25, 95% CI: 0.90-1.74, Zâ=â1.34, Pâ=â.18), or histologic type (OR: 1.17, 95% CI: 0.85-1.60, Zâ=â0.96, Pâ=â.34) in ovarian cancer. Furthermore, B7-H4 expression was significantly associated with a worse progression-free survival (PFS) (HR: 1.30, 95% CI: 1.17-1.45, Zâ=â4.79, Pâ<â.05). CONCLUSION: B7-H4 expression was related to ovarian cancer, but not to patients' clinicopathologic characteristics. High B7-H4 expression was negatively correlated with survival outcome, suggesting that B7-H4 plays an essential role in poor prognosis in ovarian cancer patients.
Assuntos
Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Inibidor 1 da Ativação de Células T com Domínio V-Set/biossíntese , Biomarcadores Tumorais , China , Intervalo Livre de Doença , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico , Linfócitos T/metabolismoRESUMO
PURPOSE: Prostate cancer (PCa) causes a common male urinary system malignant tumour, and the molecular mechanisms of PCa are related to the abnormal regulation of various signalling pathways. An increasing number of studies have suggested that mRNAs, miRNAs, lncRNAs, and TFs could play important roles in various biological processes that are associated with cancer pathogenesis. This study aims to reveal functional genes and investigate the underlying molecular mechanisms of PCa with bioinformatics. METHODS: Original gene expression profiles were obtained from the GSE64318 and GSE46602 datasets in the Gene Expression Omnibus (GEO). We conducted differential screens of the expression of genes (DEGs) between two groups using the online tool GEO2R based on the R software limma package. Interactions between differentially expressed miRNAs, mRNAs and lncRNAs were predicted and merged with the target genes. Co-expression of miRNAs, lncRNAs and mRNAs was selected to construct mRNA-miRNA-lncRNA interaction networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for the DEGs. Protein-protein interaction (PPI) networks were constructed, and transcription factors were annotated. Expression of hub genes in the TCGA datasets was verified to improve the reliability of our analysis. RESULTS: The results demonstrate that 60 miRNAs, 1578 mRNAs and 61 lncRNAs were differentially expressed in PCa. The mRNA-miRNA-lncRNA networks were composed of 5 miRNA nodes, 13 lncRNA nodes, and 45 mRNA nodes. The DEGs were mainly enriched in the nuclei and cytoplasm and were involved in the regulation of transcription, related to sequence-specific DNA binding, and participated in the regulation of the PI3K-Akt signalling pathway. These pathways are related to cancer and focal adhesion signalling pathways. Furthermore, we found that 5 miRNAs, 6 lncRNAs, 6 mRNAs and 2 TFs play important regulatory roles in the interaction network. The expression levels of EGFR, VEGFA, PIK3R1, DLG4, TGFBR1 and KIT were significantly different between PCa and normal prostate tissue. CONCLUSION: Based on the current study, large-scale effects of interrelated mRNAs, miRNAs, lncRNAs, and TFs established a new prostate cancer network. In addition, we conducted functional module analysis within the network. In conclusion, this study provides new insight for exploration of the molecular mechanisms of PCa and valuable clues for further research into the process of tumourigenesis and its development in PCa.