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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 56-62, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027253

RESUMO

OBJECTIVE: To investigate the expression and significance of B and T lymphocyte weakening factor (BTLA) in patients with chronic myelomonocytic leukemia (CMML). METHODS: Real-time PCR was used to detect the expression of BTLA and its ligand HVEM mRNA in 11 patients with chronic myelomonocytic leukemia and 11 normal donors. Flow cytometry was used to detect expression of BTLA and its HVEM on the cell surface of peripheral blood T lymphocytes and γδ T cells. RESULTS: The median values of BTLA and its ligand HVEM mRNA expression in peripheral blood of patients with CMML were 0.009% and 559.4%, respectively, which were significantly lower than those of normal controls (0.053% and 1031%)(P<0.001). The expression level of BTLA and HVEM on cell surface of peripheral lymphocytes was not significantly different from that in normal controls (P=0.3031 and 0.2576), however, the proportion of peripheral blood T lymphocytes in patients with CMML (median: 37.73%) was significantly lower than that in controls (median 69.23%)(P=0.0005). The expression of BTLA on the surface of γδ T cells in peripheral blood of patients with CMML (median: 23.26%) was significantly lower than that of the controls (median: 52.64%) (P<0.05), and there was no significant abnormality in HVEM expression (P=0.2791). CONCLUSION: The expression of BTLA and its ligand HVEM, the proportion of T lymphocytes and the expression of BTLA on the surface of γδ T cells in patients with CMML are reduced. The effects of these abnormalities on T cell function and prognosis and efficacy of patients need to be further observed.


Assuntos
Leucemia Mielomonocítica Crônica , Receptores Imunológicos/genética , Membro 14 de Receptores do Fator de Necrose Tumoral/genética , Humanos , Leucemia Mielomonocítica Crônica/genética , Ligantes , Linfócitos T
2.
World Neurosurg ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31927122

RESUMO

OBJECTIVE: Meningiomas are among the most common primary intracranial tumors. Up to 20% of cases will show increased malignancy at histological examination (World Health Organization grade II or III). Effective pharmacotherapy, except for radiotherapy, is lacking. Therefore, it is necessary to study the pathogenesis of malignant meningioma to provide more treatment strategies. METHODS: RNA sequencing and micro-RNA (miRNA) microarray detection were applied to identify differentially expressed messenger RNAs (mRNAs) and miRNAs in benign and malignant meningioma. The miRDB and TargetScan databases were used to predict the potential interaction between miRNAs and mRNAs. A proliferation assay was used to evaluate the cell growth. A wound healing assay and Transwell assay were performed to assess the cell migration and invasion abilities, respectively. The interaction between miRNA and mRNA was identified using a luciferase reporter assay. RESULTS: We found fatty acid synthase (FASN) was significantly upregulated in malignant meningioma compared with benign meningioma. Knockdown of FASN significantly inhibited proliferation, migration, and invasion of IOMM-Lee cells. Moreover, miR-195 was verified to directly target FASN using a luciferase reporter assay. Upregulation of miR-195 also significantly inhibited proliferation, migration, and invasion of IOMM-Lee cells. Furthermore, we performed bioinformatics analysis to predict the competing endogenous RNAs (ceRNAs) and found that NUP210, SPIRE2, SLC7A1, and DMTN might function as ceRNAs of FASN by sponging miR-195 in meningioma. CONCLUSIONS: Our results have suggested a tumor suppressive role for miR-195 in the tumorigenesis and progression of malignant meningioma by targeting FASN. In addition, NUP210, SPIRE2, SLC7A1, and DMTN might act as ceRNAs to regulate FASN expression by sponging miR-195.

3.
Neuroimage ; 206: 116334, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31704295

RESUMO

Executive function (EF) refers as to a set of high-level cognitive abilities that are critical to many aspects of daily life. Despite its importance in human daily life, the neural networks responsible for the development of EF in childhood are not well understood. The present study thus aimed to examine the development of task-dependent brain network organization and its relationship to age-related improvements in EF. To address this issue, we recruited eighty-eight Chinese children ranging in age from 7 to 12 years old, and collected their functional magnetic resonance imaging (fMRI) data when they performed an EF task. By utilizing graph theory, we found that the task-dependent brain network modules became increasingly segregated with age. Specifically, the intra-module connections within the default-mode network (DMN), frontal-parietal network (FPN) and sensorimotor network (SMN) increased significantly with age. In contrast, the inter-module connections of the visual network to both the FPN/SMN decreased significantly with age. Most importantly, modular segregation of the FPN significantly mediated the relationship between age and EF performance. These findings add to our growing understanding of how development changes in task-dependent brain network organization support vast behavioral improvements in EF observed during childhood.

4.
J Infect Public Health ; 13(1): 34-39, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31235340

RESUMO

BACKGROUND: Norovirus (NoV) is recognized as a leading global cause of viral acute gastroenteritis (AGE). To better understand the prevalence and genotypic patterns of NoV infection in Southeast China, we conducted a retrospective study of diarrheal syndrome surveillance of NoV and analyzed the epidemiological characteristics of AGE cases and phylogenetic evolution of NoV strains. METHODS: 1464 AGE patients in two diarrhea surveillance sentinel hospitals were sampled during 2016 and 2017. NoV Positive samples were genotyped by ORF1/ORF2 overlapping regional gene sequencing. Sequences analyses of the NoV genotypes were confirmed by online NoV Genotyping Tool and the phylogenetic analysis was constructed by MEGA 7.0. RESULTS: 139 (9.49%) of the AGE specimens were NoV positive. The GII strain was the main geno-group in NoV infected patients. At least 12 NoV genotypes and seven recombinant strains were detected. Major NoV genotypic transformations were GII.Pe/GII.4, GII.P17/GII.17 and GII.Pe/GII.17 in 2016 to GII.P16/GII.2, GII.P17/GII.17 and GII.Pe/GII.4 in 2017. Phylogenetic analysis showed that GII.P16/GII.2 recombinant strains clustered with those detected in the USA, Russia and Japan in 2016. CONCLUSION: We characterized the molecular epidemiology of NoV infection in AGE patients during 2016-2017. The main three NoV GII genotypes circulating in the population of Taizhou were GII.P17/GII.17, GII.Pe/GII.4 and GII.P16/GII.2.The GII.P16/GII.2 genotype has become the predominant strain since first quarter 2017. Monitoring of the NoV genotypic shift is important for the prevention and control of AGE.

5.
J Neurooncol ; 146(1): 207-217, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31853837

RESUMO

PURPOSE: Diffuse low-grade and intermediate-grade gliomas, also known as lower-grade gliomas (LGGs), are a class of central nervous system tumors. Overall survival varies greatly between patients, highlighting the importance of evaluating exact outcomes to facilitate individualized clinical management. We aimed to identify an mRNA-based prognostic signature to predict the survival of patients with LGGs. METHODS: A total of 874 LGGs from two public datasets were included. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select the most prognostic mRNAs and build a risk score. A nomogram incorporating the risk score and clinical factors was established for individualized survival prediction. The performance of the nomogram was assessed in the training set (329 patients), internal validation set (140 patients), and external validation set (405 patients). RESULTS: 21 most prognostic mRNAs remained following the LASSO Cox regression. The 21-mRNA signature successfully stratified patients into high- and low-risk groups (P < 0.001 for all datasets in Kaplan-Meier analysis). Subsequent gene set enrichment analysis identified 19 essential biological processes in high-risk LGGs. Furthermore, a nomogram incorporating the risk score, age, grade, and 1p/19q status was developed with favorable calibration and high predictive accuracy in the training set and validation sets (C-index: 0.877, 0.878, and 0.812, respectively). CONCLUSION: The 21-mRNA signature has reliable prognostic value for LGGs and might facilitate the effective stratification and individualized management of patients.

6.
Adv Sci (Weinh) ; 6(23): 1901152, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31832311

RESUMO

Identifying the mechanisms underlying cognitive development in early life is a critical objective. The expression of insulin-like growth factor binding protein 2 (IGFBP2) in the hippocampus increases during neonatal development and is associated with learning and memory, but a causal connection has not been established. Here, it is reported that neurons and astrocytes expressing IGFBP2 are distributed throughout the hippocampus. IGFBP2 enhances excitatory inputs onto CA1 pyramidal neurons, facilitating intrinsic excitability and spike transmission, and regulates plasticity at excitatory synapses in a cell-type specific manner. It facilitates long-term potentiation (LTP) by enhancing N-methyl-d-aspartate (NMDA) receptor-dependent excitatory postsynaptic current (EPSC), and enhances neurite proliferation and elongation. Knockout of igfbp2 reduces the numbers of pyramidal cells and interneurons, impairs LTP and cognitive performance, and reduces tonic excitation of pyramidal neurons that are all rescued by IGFBP2. The results provide insight into the requirement for IGFBP2 in cognition in early life.

7.
Adv Sci (Weinh) ; 6(23): 1901991, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31832324

RESUMO

Few-layer black phosphorus (FL-BP) has been intensively studied due to its attractive properties and great potential in electronic and optoelectronic applications. However, the intrinsic instability of FL-BP greatly limits its practical application. In this study, the amphiphobic FL-BP is achieved by functionalization of 1H,1H,2H,2H-perfluorooctyltrichlorosilane (PFDTS) on the surface of FL-BP. The obtained PFDTS coated FL-BP (FL-BP/PFDTS) demonstrates enhanced stability, which is not observed during significant degradation for 2 months in high moisture content environment (95% humidity). Particularly, attributing to the surface amphiphobicity, FL-BP/PFDTS exhibits strong surface water repellency in the presence of oleic acid (as the contaminant), while other passivation coating layers (such as hydrophilic or hydrophobic coating) become hydrophilicity under such conditions. Owing to this advantage, the obtained FL-BP/PFDTS demonstrates enhanced stability in high moisture content environment for 2 months, even though the surface is contaminated by oil liquid or other organic solvents (such as oleic acid, CH2Cl2, and N-methyl-2-pyrrolidone). The passivation of FL-BP by amphiphobic coating provides an effective approach for FL-BP stabilization toward future applications.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31725399

RESUMO

Sample balancing includes sample selection and sample reweighting. Sample selection aims to remove some bad samples that may lead to bad local optima. Sample reweighting aims to assign optimal weights to samples to improve performance. In this article, we integrate a sample selection method based on self-paced learning into deep learning frameworks and study the influence of different sample selection strategies on training deep networks. In addition, most of the existing sample reweighting methods mainly take per-class sample number as a metric, which does not fully consider sample qualities. To improve the performance, we propose a novel metric based on the multiview semantic encoders to reweight the samples more appropriately. Then, we propose an optimization mechanism to embed sample weights into loss functions of deep networks, which can be trained in end-to-end manners. We conduct experiments on the CIFAR data set and the ImageNet data set. The experimental results demonstrate that our proposed sample balancing method can improve the performances of deep learning methods in several visual recognition tasks.

9.
J Orthop Surg Res ; 14(1): 343, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694690

RESUMO

OBJECTIVES: The purpose of this study is to identify the factors that influence the length of stay (LOS) in total knee arthroplasty (TKA) patients with an enhanced recovery after surgery (ERAS) program. METHODS: Information from 167 patients (31 males and 136 females, range from 43 years to 88 years old) who underwent the unilateral elective primary TKA from January 2017 to January 2019 were reviewed retrospectively. Factors were analyzed by single-factor variance and multi-factor linear regression. RESULTS: By single-factor variance analysis, American Society of Anesthesiologists (ASA) physical status classification system, pre-operation albumin, pre-operation erythrocyte sedimentation rate (ESR), primary and merge diseases, hidden blood loss, and length of operation were correlated with LOS (P < 0.05). Multi-factor linear regression results suggested that gender, ASA class, pre-operation Alb, and pre-operation ESR were associated with LOS (P < 0.05). Moreover, ASA class 3 (B value 4.84), pre-operation Alb < 30 g/L (B value 18.33), and pre-operation ESR > 15 mmol/h (B value 2.21) could increase the LOS, while males (B value - 3.56) had a shortened LOS. CONCLUSIONS: Overall, our research found that female, ASA class 3, pre-operation Alb < 30 g/L, and pre-operation ESR > 15 mmol/h could extend LOS in TKA patients with ERAS.

10.
ACS Omega ; 4(6): 11285-11292, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31460231

RESUMO

The K2S2O8-mediated hydroxyalkylation of 2H-benzothiazoles with aliphatic alcohols in aqueous solution was described. The mild and convenient protocol generated a series of hydroxyalkylated benzothiazoles in moderate to good yields. Besides, benzimidazole and ethers were also compatible in this reaction, leading to corresponding C2 ether-substituted heteroarenes.

11.
Biosens Bioelectron ; 142: 111520, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31330418

RESUMO

The excellent conductivity matching of two-dimensional (2D) semiconductor nanomaterials (e.g. MoS2) with cancer cell plays an important role in ultrasensitive label-free impedimetric detection of circulating tumor cells (CTC) (<1 cell/mL). Firstly, 2D semiconductor materials (e.g. 2D MoS2) exfoliated by folic acid (FA) is used to construct MoS2/FA-modified gold electrode (AuE/MoS2/FA). Then, the fabricated electrode is applied for HeLa cell detection in a linear range from 1 to 105 cell/mL with a detection limit of 0.43 cell/mL (S/N = 3). The detection mechanism of high sensitivity might be owing to the electric conductivity matching of MoS2 (0.14 S/m) to cancer cell (0.13-0.23 S/m). A negligible conductivity change induced by cancer cell will produce a large impedance change of semiconductor electrode. Furthermore, HeLa cells dispersed in healthy blood samples are detected by suggested cytosensor in a linear range from 50 to 105 cell/mL with a detection limit of 52.24 cell/mL (S/N = 2). Finally, we demonstrate that the cytosensor is capable of differentiating patients of cervical and liver cancers by the real CTC analysis from healthy control.

12.
Clin Chim Acta ; 497: 6-12, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31279693

RESUMO

BACKGROUND: Interleukin-33 is recently identified as a brain injury biomarker. We determined whether serum interlerukin-33 concentrations are associated with inflammation, severity and prognosis after traumatic brain injury (TBI). METHODS: We detected serum interlerukin-33 concentrations of 102 healthy controls and 102 severe TBI patients, as well as serum concentrations of 3 inflammatory biomarkers (interleukin-6, tumor necrosis factor-alpha and C-reactive protein) and 7 cell-specific proteins (myelin basic protein, glial fibrillary astrocyte protein, S100B, neuron-specific enolase, phosphorylated axonal neurofilament subunit H, Tau and ubiquitin carboxyl-terminal hydrolase L1) in 102 severe TBI patients. The recorded poor prognosis variables included acute lung injury, acute traumatic coagulopathy, progressive hemorrhagic injury, posttraumatic cerebral infarction and six-month mortality and poor outcome (Glasgow score of 1-3). RESULTS: Median interlerukin-33 concentration of patients (692 pg/mL) was substantially raised, as compared to controls. Interlerukin-33 concentrations were significantly correlated with Glasgow coma scale (GCS) score and the preceding biomarkers concentrations. Interlerukin-33 concentration > 692 pg/mL emerged as an independent prognostic predictor and its discriminatory capability exceeded those of the above-mentioned inflammatory biomarkers concentrations and was in the range of GCS scores and the aforementioned cell-specific proteins concentrations. CONCLUSION: Ascending serum interlerukin-33 concentrations could reflect inflammation, severity and worse prognosis following TBI.

13.
Pest Manag Sci ; 75(11): 2892-2900, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31050111

RESUMO

BACKGROUND: In recent years, carboxamide fungicides, targeting succinate dehydrogenase (SDH), have shown highly efficient and broad spectrum fungicidal activity. Structure-activity relationship (SAR) results for these commercial fungicides show that the carboxamide group was a key active group. This is useful information for the discovery of new pyrazole carboxamide derivatives with fungicidal activity. RESULTS: Twenty-seven novel pyrazole carboxamides were designed and synthesized. Their fungicidal activities against Gibberella zeae, Phytophthora infestans, Phytophthora capsici, Rhizoctonia solani, Alternaria solani, Botrytis cinerea, Fusarium oxysporum, Cercospora arachidicola, Sclerotinia sclerotiorum and Physalospora piricola were tested; derivatives possessed excellent inhibitory at 50 mg L-1 in particular. Furthermore, some pyrazole carboxamides exhibited remarkably high activities against Sclerotinia sclerotiorum in vitro with EC50 values of 2.04 to 15.2 µg mL-1 . In addition, some compounds also exhibited high activities against Physalospora piricola, Cercospora arachidicola and Phytophthora capsici. Inhibition activities against SDH proved that the designed analogues were effective at the enzyme level. The SAR of these pyrazole carboxamides was studied by using the docking method. CONCLUSION: It is possible that pyrazole carboxamides, which exhibit good activity against Sclerotinia sclerotiorum, can be further optimized as a lead compounds of carboxamide fungicides. © 2019 Society of Chemical Industry.


Assuntos
Ascomicetos/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Fungos Mitospóricos/efeitos dos fármacos , Phytophthora infestans/efeitos dos fármacos , Pirazóis/farmacologia , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Pirazóis/síntese química , Pirazóis/química , Relação Estrutura-Atividade
14.
Neurosurgery ; 2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31081882

RESUMO

BACKGROUND: Limited data existed to guide the management of intraspinal neurenteric cysts (ISNECs). OBJECTIVE: To evaluate the risk factors for progression-free survival (PFS), elucidate the radiological features of ISNECs, and propose a treatment protocol. METHODS: From 2003 to 2015, 121 patients with pathologically confirmed ISNECs treated at our institute were included in this study. Pertinent risk factors were evaluated. RESULTS: Gross total resection (GTR) was achieved in 55 (44.6%) patients; 106 (87.6%), 12 (9.9%), and 3 (2.5%) ISNECs were classified as Wilkins A, B, and C, respectively. After a median follow-up duration of 64.2 mo, recurrence occurred in 25 (22.7%) patients, with a median PFS time of 43.1 mo. The actuarial PFS rates at 5 and 10 yr were 73.2% and 66.2%, respectively. The actuarial overall survival rates at 5 and 10 yr were 100% and 97.6%, respectively. Non-GTR (hazard ratio [HR], 5.836; 95% confidence interval [CI], 1.698-20.058; P = .005), Wilkins B/C (HR, 3.129; 95% CI, 1.009-9.702; P = .048), and a history of surgical resection (HR, 3.690; 95% CI, 1.536-8.864; P = .004) were adverse factors. CONCLUSION: GTR and Wilkins A were favorable factors for PFS. If tolerable, GTR alone was advocated as an optimal treatment. Because of the benign nature and favorable prognosis, non-GTR was an alternative if GTR failed. Close follow-up was needed because of the recurrent tendency of ISNEC. Future study with a large cohort is necessary to verify our findings.

15.
Ticks Tick Borne Dis ; 10(3): 647-650, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30826250

RESUMO

Severe fever with thrombocytopenia syndrome virus (SFTSV) has been emerging and has caused many human cases in China, Japan and Korea. Some studies speculated that SFTSV was transmitted with bird migration among these countries. Notably, SFTS cases have been identified in a Chinese island named Dachen which is situated southwest of Japan and Korea. In this study, we conducted a serum survey of SFTSV antibodies among inhabitants of the island. A total of 439 serum specimens were collected in June 2018. All serum samples were tested for total antibodies and IgM antibody with double-antigen sandwich ELISA method. The rates of seropositivity for SFTSV total antibodies and IgM antibody were 3.0% (95% CI 1.4-4.6) and 0.5% (2/439), respectively. The median age of all participants was 61 years and all seropositive samples were all from inhabitants aged >50 years. The differences of seroprevalence between different gender groups and different age groups were not significant. However, seroprevalence varied significantly among different villages (P = 0.033). Our results showed that some inhabitants of Dachen Island had been infected with SFTSV, and some ticks and host animals of the island carry SFTSV. Comprehensive measures should be conducted to prevent the occurrence of SFTS cases in the island.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Bunyaviridae/epidemiologia , Infecções por Bunyaviridae/imunologia , Estudos Soroepidemiológicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , China/epidemiologia , Feminino , Geografia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Ilhas , Masculino , Pessoa de Meia-Idade , Phlebovirus , Carrapatos/virologia , Adulto Jovem
16.
J Neurosurg ; : 1-12, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30835686

RESUMO

OBJECTIVE: The overall survival and pertinent adverse factors for primary intracranial malignant melanoma (PIMM) have not been previously determined. This aim of this study was to determine the rates of progression-free survival (PFS) and overall survival (OS) and identify the adverse factors for PIMM. METHODS: This study included 15 cases from the authors' own series and 100 cases with detailed clinical data that were obtained from the literature from 1914 to 2018 using the Ovid Medline, EMBASE, PubMed, Cochrane, and EBSCO databases. Patient demographics, treatment (surgery, chemotherapy, and radiotherapy [RT]), PFS, and OS were reviewed. Data from prior publications were processed and used according to PRISMA guidelines. RESULTS: Diffuse lesions were identified in 24 (20.9%) patients, who had a younger age (p < 0.001). The mean follow-up time was 16.6 months, and 76 (66.1%) deaths occurred. The 6-month, 1-year, 3-year, and 5-year OS rates of the whole cohort were 62.8%, 49.9%, 28.9%, and 17.2%, respectively, with an estimated median survival time (EMST) of 12.0 months. The multivariate analysis revealed that gross-total resection (GTR) (HR 0.299, 95% CI 0.180-0.497, p < 0.001), radiotherapy (HR 0.577, 95% CI 0.359-0.929, p = 0.024), and chemotherapy (HR 0.420, 95% CI 0.240-0.735, p = 0.002) predicted a better OS. The EMST was 5.0 months in patients with diffuse-type PIMM and 13.0 months in patients with the solitary type. Patients receiving GTR with adjuvant RT and/or chemotherapy (GTR + [RT and/or chemo]) had significantly higher 1-year and 5-year OS rates (73.0% and 40.1%, respectively) and a longer EMST (53 months) than patients who underwent GTR alone (20.5 months) or RT and/or chemotherapy without GTR (13.0 months). CONCLUSIONS: Optimal outcomes could be achieved by radical resection plus postoperative radiotherapy and/or chemotherapy. Patients with diffuse PIMM have a more severe clinical spectrum and poorer survival than patients with solitary PIMM. Immunotherapy and targeted therapy show promise as treatment options for PIMM based on results in patients with brain metastases from extracranial melanoma.

17.
Chin Med J (Engl) ; 132(5): 569-576, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30741829

RESUMO

BACKGROUND: Glucocorticoids have been widely used to treat patients with chronic obstructive pulmonary disease (COPD). Nevertheless, corticosteroid insensitivity is a major barrier to the effective treatment of COPD and its mechanism remains unclear. This study aimed to evaluate the effect of cathelicidin LL-37 on corticosteroid insensitivity in COPD rat model, and to explore the involved mechanisms. METHODS: COPD model was established by exposing male Wistar rats to cigarette smoke combined with intratracheal instillation of lipopolysaccharide (LPS). Inhaled budesonide and LL-37 were consequently applied to COPD models separately or collectively to confirm the effects on inflammatory cytokines (tumor necrosis factor [TNF]-α and transforming growth factor [TGF]-ß) by enzyme-linked immunosorbent assay (ELISA) and lung tissue histopathological morphology. Expression of histone deacetylase-2 (HDAC2) and phosphorylation of Akt (p-AKT) in lung were also measured. RESULTS: Briefly, COPD model rats showed an increased basal release of inflammatory cytokines (lung TNF-α: 45.7 ±â€Š6.1 vs. 20.1 ±â€Š3.8 pg/mL, P < 0.01; serum TNF-α: 8.9 ±â€Š1.2 vs. 6.7 ±â€Š0.5 pg/mL, P = 0.01; lung TGF-ß: 122.4 ±â€Š20.8 vs. 81.9 ±â€Š10.8 pg/mL, P < 0.01; serum TGF-ß: 38.9 ±â€Š8.5 vs. 20.6 ±â€Š2.3 pg/mL, P < 0.01) and COPD related lung tissue histopathological changes, as well as corticosteroid resistance molecular profile characterized by an increase in phosphoinositide 3-kinase (PI3K)/Akt (0.5 ±â€Š0.1 fold of control vs. 0.2 ±â€Š0.1 fold of control, P = 0.04) and a decrease in HDAC2 expression and activity (expression: 13.1 ±â€Š0.4 µmol/µg vs. 17.4 ±â€Š1.1 µmol/µg, P < 0.01; activity: 1.1 ±â€Š0.1 unit vs. 1.4 ±â€Š0.1 unit, P < 0.01), compared with control group. In addition, LL-37 enhanced the anti-inflammatory effect of budesonide in an additive manner. Treatment with combination of inhaled corticosteroids (ICS) and LL-37 led to a significant increase of HDAC2 expression and activity (expression: 15.7 ±â€Š0.4 µmol/µg vs. 14.1 ±â€Š0.9 µmol/µg, P < 0.01; activity: 1.3 ±â€Š0.1 unit vs. 1.0 ±â€Š0.1 unit, P < 0.01), along with decrease of p-AKT compared to budesonide monotherapy (0.1 ±â€Š0.0 fold of control vs. 0.3 ±â€Š0.1 fold of control, P < 0.01). CONCLUSIONS: This study suggested that LL-37 could improve the anti-inflammatory activity of budesonide in cigarette smoke and LPS-induced COPD rat model by enhancing the expression and activity of HDAC2. The mechanism of this function of LL-37 might involve the inhibition of PI3K/Akt pathway.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Glucocorticoides/metabolismo , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Fumar/efeitos adversos , Animais , Histona Desacetilase 2/metabolismo , Humanos , Inflamação/induzido quimicamente , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(1): 221-226, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30738474

RESUMO

OBJECTIVE: To investigate the effects of exosomes from human umbilical cord mesenchymal stem cells on the development of Treg and TH17 cells. METHODS: Exosomes from the serum-free-culture supernatants of hUC-MSC were harvested by ultracentrifugation. The electron microscopy, nanoparticle tracking analysis and western blot were used to identify the hUC-MSC-exosomes, such as the morphology, the paticle chameter, and the protein content. The PBMC stimulated with anti-CD3/CD28 were incubated with the exosomes for five days, and then the percentage changes of Treg and TH17 cells were analyzed by using flow cytometry. RESULTS: The hUC MSC-derived exosomes were saucer-like in morphology the averge diameter was approximately 142 nm. They were identified as positive for CD9 and CD63. Flow cytometry showed that the proportion of CD4+CD25+Foxp3+ Treg cells in the PBMC were significantly higher, but the proportion of CD4+IL17A+ T cells in the hUC-MSC-exosome group was obviously lower than that in the group without the hUC-MSC-exosom (control group) (P<0.05). CONCLUSION: The hUC-MSC-exosomes have an immunomodulatory effect on T cells in vitro by increasing the ratio of Treg and reducing the ratio of TH17 cells, expecting the hUC-MSC-exosom as a novel cell-free target for immunotherapy.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Humanos , Leucócitos Mononucleares , Linfócitos T Reguladores , Células Th17 , Cordão Umbilical
19.
Inj Prev ; 25(6): 507-513, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30337353

RESUMO

OBJECTIVES: Injury prevention should be informed by timely surveillance data. Unfortunately, most injury surveillance only captures patients with severe injuries and is not available in real time, hampering prevention efforts. We aimed to develop and pilot a simple injury surveillance strategy that can be integrated into routine emergency department (ED) workflow to collect more robust mechanism of injury information at time of visit for all injured ED patients with minimal impact on workflow. METHODS: We reviewed ED injury surveillance systems and considered ED workflow. Forms were developed to collect injury-related information on ED patients and refined to address workload concerns raised by key stakeholders. Research assistants observed ED staff as they registered injured patients and noted the time required to collect data and any ambiguities or concerns encountered. Interobserver agreement was recorded. RESULTS: Injury surveillance questions were based on a modification of the International Classification of External Causes of Injury. Research assistants observed 222 injured patients being admitted by registration clerks. The mean time required to complete the surveillance form was 64.9 s (95% CI 59.9 s to 69.9 s) for paper-based forms (120 cases) and 44.5 s (95% CI 41.7s to 47.4s) with direct electronic data entry (102 cases). Interobserver agreement (26 cases) was 100% for intent (kappa=1.0) of injury and 96% for mechanism of injury (kappa=0.74). CONCLUSIONS: We report a simple injury surveillance strategy that ED staff can use to collect meaningful injury data in real time with minimal impact on workflow. This strategy can be adapted to enhance regional injury surveillance efforts.

20.
Clin Chim Acta ; 488: 25-30, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30385279

RESUMO

BACKGROUND: Translocator protein (TP) is related to inflammation and is involved in brain injury. The objective of this study was to ascertain whether serum TP concentrations are associated with the severity and prognosis of traumatic brain injury (TBI). METHODS: We quantified the serum concentrations of TP in 106 healthy controls and 106 patients with severe TBI. Recorded prognostic variables included acute lung injury, acute traumatic coagulopathy, progressive hemorrhagic injury, posttraumatic cerebral infarction, 6-month mortality and 6-month poor outcome (Glasgow Outcome Scale score of 1-3). Trauma severity was assessed by Glasgow coma scale (GCS) score. Extent of inflammatory response was indicated by serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and C-reactive protein (CRP) concentrations. RESULTS: Patients had significantly higher serum TP concentrations than controls. Among patients, serum TP concentrations strongly and independently correlated with GCS score and serum IL-6, TNF-a and CRP concentrations. Serum TP was identified as an independent predictor for the preceding prognostic variables, its prognostic predictive ability was similar to that of GCS score and it also significantly improved prognostic predictive ability of GCS score. CONCLUSION: Serum TP may be intimately linked with in inflammation, disease progression and poor prognosis in TBI patients.


Assuntos
Lesões Encefálicas Traumáticas/sangue , Receptores de GABA/sangue , Adolescente , Adulto , Idoso , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
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