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1.
J Infect Dis ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33031517

RESUMO

BACKGROUND: Cytomegalovirus (CMV) can cause congenital infection and is the leading cause of nongenetic newborn disabilities. V160, a conditionally replication-defective virus, is an investigational vaccine under evaluation for prevention of congenital CMV. The vaccine was well tolerated and induced both humoral and cellular immunity in CMV-seronegative trial participants [NCT10986010]. T-cell mediated immunity is important for immune control of CMV. Here we describe efforts to understand the quality attributes of the T-cell responses induced by vaccination. METHODS: Using multicolor flow cytometry, we analyzed vaccine-induced T-cells for memory phenotype, antigen specificity, cytokine profiles, and cytolytic potential. Moreover, antigen-specific T-cells were sorted from four participants and next generation sequencing was used to trace clonal lineage development during the course of vaccination using T-cell receptor ß-chain (TCRß) sequences as identifiers. RESULTS: The results demonstrated that vaccination elicited polyfunctional CD4 and CD8 T-cells to two dominant antigens, pp65 and IE1, with a predominantly effector phenotype. Analysis of TCR repertoires showed polyclonal expansion of pp65- and IE1-specific T-cells after vaccination. CONCLUSION: V160 induced a genetically diverse and polyfunctional T-cell response and the data support further clinical development of V160 for prevention of CMV infection and congenital transmission.

2.
Front Immunol ; 11: 2176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013914

RESUMO

Chemokine receptor cxcr4 and its ligand cxcl12 have evolved two paralogs in the teleost lineage. In this study, we have identified four duplicated cxcr4 and cxcl12 genes from hexaploid gibel carp, Carassius gibelio, respectively. Cgcxcr4bs and Cgcxcl12as were dynamically and differentially expressed in immune-related tissues, and significantly up-regulated in head kidney and spleen after crucian carp herpesvirus (CaHV) infection. Blocking Cxcr4/Cxcl12 axis by injecting AMD3100 brought more severe bleeding symptom and lower survival rate in CaHV-infected fish. AMD3100 treatment also suppressed the up-regulation of key antiviral genes in head kidney and spleen, and resulted in more acute replication of CaHV in vivo. Consistently, the similar suppression of up-regulated expression of key antiviral genes were also observed in CAB cells treated by AMD3100 after poly(I:C) stimulation. Finally, MAPK3 and JAK/STAT were identified as the possible pathways that CgCxcr4s and CgCxcl12s participate in to promote the antiviral response in vitro.

3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 4126-4129, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33018906

RESUMO

A surface electromyography (sEMG) detector, that not only removes stimulation artifacts entirely but also increases the recording time, has been developed in this paper. The sEMG detector consists of an sEMG detection circuit and a stimulation isolator. The sEMG detection circuit employs a stimulus isolate switch (SIS), a blanking (BLK) and non-linear feed-back (NFB) circuit to remove the artifacts and to increase the recording time. In the SIS, the connection between stimulator and stimulation electrodes, along with the stimulation electrodes and the ground are controlled by an opto-isolator, and the connection of instrument amplifier and the recording electrodes are controlled by CMOS-based switches. The mode switches of the BLK and the NFB circuit also employs CMOS-based switches. By an accurate timing adjustment, the voluntary EMG can be recorded during electrical stimulation. Two 6 able-bodied experiments have been performed to test the three anti-artifact sEMG detector: BLK, BLK&SIS, BLK&SIS&NFB. The results indicate that the BLK&SIS&NFB proposed in this work effectively removes stimulus artifacts and M-waves, and has a longer recording time compared with BLK and BLK&SIS circuits.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33020156

RESUMO

Alternative therapeutic options are urgently needed against multidrug-resistant E. coli infections, especially in situations of pre-existing tigecycline and colistin resistances. Here, we investigated synergistic activity of the antiretroviral drug zidovudine in combination with tigecycline or colistin against E. coli harboring tet(X) and mcr-1 in vitro and in a murine thigh infection model. Zidovudine and tigecycline/colistin combinations achieved synergistic killing and significantly decreased bacterial burdens by >2.5 log10cfu/g in thigh tissues compared to each monotherapy.

5.
Genes Genomics ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040302

RESUMO

BACKGROUND: The overexpression of TSLP and DNA methylation in asthma were both risk factors the relationship was not clear. OBJECTIVE: This study aimed to investigate the relationship between methylation status of TSLP promoter and mRNA/protein expression in asthmatic airway epithelial cells. METHODS: Human bronchial epithelial cells were cultured in vitro and divided into: Control group, treated with PBS, model group, sensitized with LPS (10 µg/mL) for 12 h (37 °C, 5% CO2). Other groups were cultured with the pCMV3 plasmid (M + NC/pCMV), pGPH1 plasmid (M + NC/pGPH), DNMT1/pCMV3 plasmid (M + DNMT1/pCMV), and DNMT1/pGPH1 plasmid (M + DNMT1/pGPH) for 48 h. The expression of DNA methyltransferase 1 and TSLP were measured using real-time PCR and western blotting. RESULTS: Compared with the control group, TSLP mRNA (1.00 ± 0.00 vs. 2.82 ± 0.81 vs. 1, P < 0.001) and protein (1.07 ± 0.04 vs. 1.46 ± 0.11, P < 0.01) were significantly greater, and the methylation of promoter was lower (92.75 ± 1.26 vs. 58.57 ± 3.34, P < 0.05) in the model group. Compared with the model group, TSLP mRNA (2.82 ± 0.81 vs. 1.17 ± 0.10, P < 0.001) decreased, but TSLP promoter methylation increased (58.57 ± 3.34 vs. 92.58 ± 7.30, P < 0.05) in M + DNMT1/pCMV. TSLP mRNA and protein were higher (2.82 ± 0.81 vs. 5.32 ± 0.21, P < 0.001; 1.46 ± 0.11 vs. 1.94 ± 0.11, respectively, P < 0.01), TSLP promoter methylation was lower (58.57 ± 3.34 vs. 33.57 ± 4.29, P < 0.05) in M + DNMT1/pGPH. CONCLUSIONS: Overexpression of TSLP in asthmatic airway epithelial cells may be regulated by DNA demethylation.

6.
Front Immunol ; 11: 565099, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042144

RESUMO

Objective: Monogenic autoinflammatory diseases (AIDs) are inborn disorders caused by innate immunity dysregulation and characterized by robust autoinflammation. We aimed to present the phenotypes and genotypes of Chinese pediatric monogenic AID patients. Methods: A total of 288 pediatric patients clinically suspected to have monogenic AIDs at the Department of Pediatrics of Peking Union Medical College Hospital between November 2008 and May 2019 were genotyped by Sanger sequencing, and/or gene panel sequencing and/or whole exome sequencing. Final definite diagnoses were made when the phenotypes and genotypes were mutually verified. Results: Of the 288 patients, 79 (27.4%) were diagnosed with 18 kinds of monogenic AIDs, including 33 patients with inflammasomopathies, 38 patients with non-inflammasome related conditions, and eight patients with type 1 interferonopathies. Main clinical features were skin disorders (76%), musculoskeletal problems (66%), fever (62%), growth retardation (33%), gastrointestinal tract abnormalities (25%), central nervous system abnormalities (15%), eye disorders (16%), ear problems (9%), and cardiopulmonary disorders (8%). The causative genes were ACP5, ADA2, ADAR1, IFIH1, LPIN2, MEFV, MVK, NLRC4, NLRP3, NLRP12, NOD2, PLCG2, PSMB8, PSTPIP1, TMEM173, TNFAIP3, TNFRSF1A, and TREX1. Conclusions: The present study summarized both clinical and genetic characteristics of 18 kinds of monogenic AIDs found in the largest pediatric AID center over the past decade, with fever, skin problems, and musculoskeletal system disorders being the most prevalent clinical features. Many of the mutations were newly discovered. This is by far the first and largest monogenic AID report in Chinese pediatric population and also a catalog of the phenotypic and genotypic features among these patients.

7.
Innovation (N Y) ; : 100046, 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-33016958

RESUMO

[This corrects the article DOI: 10.1016/j.xinn.2020.100028.].

8.
Nanotechnology ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33007763

RESUMO

The increasing demand for miniaturized, wearable, and flexible electronics has promoted the development of micro power sources such as micro-supercapacitors (MSCs). This work reports a high-performance MSC based on Ti3C2Tx-layer/MnO2-nanorod with an ionic liquid gel electrolyte, achieving a high areal capacitance of 24.7 mF cm-2 within a wide voltage window of 2.5 V. The specific layer-rod interlaced structure of Ti3C2Tx/MnO2 is designed to solve the inaccessibility of large-sized ions in ionic liquids into Ti3C2Tx layers. As a result, the structure modification provides an enhancing capacitance because the expanded interspace enables a sufficient number of large-sized ions to intercalate/de-intercalate. This work provides insightful guidance for the interlaminar modification of Ti3C2Tx MXene to accommodate for high operating voltage electrolyte with large-sized ions to obtain high-performance MSCs.

9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 1679-1682, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018319

RESUMO

Epilepsy is one of the largest neurological diseases in the world, and juvenile myoclonic epilepsy (JME) usually occurs in adolescents, giving patients tremendous burdens during growth, which really needs the early diagnosis. Advanced diffusion magnetic resonance imaging (MRI) could detect the subtle changes of the white matter, which could be a non-invasive early diagnosis biomarker for JME. Transfer learning can solve the problem of insufficient clinical samples, which could avoid overfitting and achieve a better detection effect. However, there is almost no research to detect JME combined with diffusion MRI and transfer learning. In this study, two advanced diffusion MRI methods, high angle resolved diffusion imaging (HARDI) and neurite orientation dispersion and density imaging (NODDI), were used to generate the connectivity matrix which can describe tiny changes in white matter. And three advanced convolutional neural networks (CNN) based transfer learning were applied to detect JME. A total of 30 participants (15 JME patients and 15 normal controls) were analyzed. Among the three CNN models, Inception_resnet_v2 based transfer learning is better at detecting JME than Inception_v3 and Inception_v4, indicating that the "short cut" connection can improve the ability to detect JME. Inception_resnet_v2 achieved to detect JME with the accuracy of 75.2% and the AUC of 0.839. The results support that diffusion MRI and CNN based transfer learning have the potential to improve the automated detection of JME.

10.
Medicine (Baltimore) ; 99(40): e22337, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019410

RESUMO

At present, glycated hemoglobin (HbA1c) and glycated albumin (GA) are used to evaluate glycemic control in diabetic patients, but they cannot reflect insulin deficiency and/or insulin resistance.We investigated the feasibility of using estimated average glucose to fasting plasma glucose ratio (eAG/fPG ratio) to estimate insulin resistance in young adult diabetes. A total of 387 patients with type 2 diabetes were included and were stratified into 2 groups based on median values of the glycemic index ratio: the GA/A1c ratio <2.09 (n = 91) and ≥2.09 (n = 296); the eAG/fPG ratio <1.69 (n = 155) and ≥1.69 (n = 232). HbA1c, GA, fructosamine, insulin, and C-peptide levels were measured. The ratio of GA to HbA1c was calculated, and the homeostasis model assessment of ß-cell function and insulin resistance were determined. The homeostasis model assessment of insulin resistance level was significantly associated with the eAG/fPG ratio, but not with the ratio of GA to HbA1c, GA, HbA1c, and fructosamine levels. The ratio of estimated average glucose to fasting plasma glucose level correlates with insulin resistance in young adult diabetes.

11.
Comput Biol Chem ; 89: 107397, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33035753

RESUMO

Qiang-Huo-Sheng-Shi decoction (QHSSD), a classic traditional Chinese herbal formula, which has been reported to be effective in rheumatoid arthritis (RA) and osteoarthritis (OA). However, the concurrent targeting mechanism of how the aforementioned formula is valid in the two distinct diseases OA and RA, which represents the homotherapy-for-heteropathy principle in traditional Chinese medicine (TCM), have not yet been clarified. In the present study, network pharmacology was adopted to analyze the potential molecular mechanism, and therapeutic effective components of QHSSD on both OA and RA. A total of 153 active ingredients in QHSSD were identified, 142 of which associated with 59 potential targets for the two diseases were identified. By constructing the protein-protein interaction network and the compound-target-disease network, 72 compounds and 10 proteins were obtained as the hub targets of QHSSD against OA and RA. The hub genes of ESR1, PTGS2, PPARG, IL1B, TNF, MMP2, IL6, CYP3A4, MAPK8, and ALB were mainly involved in osteoclast differentiation, the NF-κB and TNF signaling pathways. Moreover, molecular docking results showed that the screened active compounds had a high affinity for the hub genes. This study provides new insight into the molecular mechanisms behind how QHSSD presents homotherapy-for-heteropathy therapeutic efficacy in both OA and RA. For the first time, a two-disease model was linked with a TCM formula using network pharmacology to identify the key active components and understand the common mechanisms of its multi-pathway regulation. This study will inspire more innovative and important studies on the modern research of TCM formulas.

12.
Int J Pharm ; : 119971, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33059014

RESUMO

Oncolytic adenovirus (OAds) has long been considered a promising biotherapeutic agent against various types of cancer owing to selectively replicate in and lyse cancer cells, while remaining dormant in healthy cells. In the last years, multiple (pre)clinical studies using genetic engineering technologies enhanced OAds anti-tumor effects in a broad range of cancers. However, poor targeting delivery, tropism toward healthy tissues, low-level expression of Ad receptors on tumor cells, and pre-existing neutralizing antibodies are major hurdles for systemic administration of OAds. Different vehicles have been developed for addressing these obstacles, such as stem cells, nanoparticles (NPs) and shielding polymers, extracellular vesicles (EVs), hydrogels, and microparticles (MPs). These carriers can enhance the therapeutic efficacy of OVs through enhancing transfection, circulatory longevity, cellular interactions, specific targeting, and immune responses against cancer. In this paper, we reviewed adenovirus structure and biology, different types of OAds, and the efficacy of different carriers in systemic administration of OAds.

13.
BMJ Open ; 10(10): e043411, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060093

RESUMO

OBJECTIVE: To compare the epidemiological characteristics and transmission dynamics in relation to interventions against the COVID-19 and severe acute respiratory syndrome (SARS) outbreak in mainland China. DESIGN: Comparative study based on a unique data set of COVID-19 and SARS. SETTING: Outbreak in mainland China. PARTICIPANTS: The final database included 82 858 confirmed cases of COVID-19 and 5327 cases of SARS. METHODS: We brought together all existing data sources and integrated them into a comprehensive data set. Individual information on age, sex, occupation, residence location, date of illness onset, date of diagnosis and clinical outcome was extracted. Control measures deployed in mainland China were collected. We compared the epidemiological and spatial characteristics of COVID-19 and SARS. We estimated the effective reproduction number to explore differences in transmission dynamics and intervention effects. RESULTS: Compared with SARS, COVID-19 affected more extensive areas (1668 vs 230 counties) within a shorter time (101 vs 193 days) and had higher attack rate (61.8 vs 4.0 per million persons). The COVID-19 outbreak had only one epidemic peak and one epicentre (Hubei Province), while the SARS outbreak resulted in two peaks and two epicentres (Guangdong Province and Beijing). SARS-CoV-2 was more likely to infect older people (median age of 52 years), while SARS-CoV tended to infect young adults (median age of 34 years). The case fatality rate (CFR) of either disease increased with age, but the CFR of COVID-19 was significantly lower than that of SARS (5.6% vs 6.4%). The trajectory of effective reproduction number dynamically changed in relation to interventions, which fell below 1 within 2 months for COVID-19 and within 5.5 months for SARS. CONCLUSIONS: China has taken more prompt and effective responses to combat COVID-19 by learning lessons from SARS, providing us with some epidemiological clues to control the ongoing COVID-19 pandemic worldwide.

15.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(4): 364-370, 2020 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-32865352

RESUMO

OBJECTIVE: To explore the association between two single nucleotide polymorphisms (SNPs), namely, rs4691383 and rs7667857, in the platelet-derived growth factor-C (PDGF-C) gene, the genotypes, environmental exposure factors, and nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Western Chinese population. METHODS: A total of 268 case-parent trios were selected, and two SNPs (rs4691383 andrs7667857) were genotyped by using polymerase chain reaction and restriction enzyme fragment length polymorphic method and direct sequencing method. Hardy-Weinberg equilibrium, linkage disequilibrium test, transmission disequilibrium test, and haplotype analysis were conducted to analyze the data. Meanwhile, the questionnaires on the epidemiology of cleft lip and palate filled by the included samples were collected, and the interaction between the genotypes of the two SNPs and environmental exposure factors was assessed by conditional logistic regression. RESULTS: The A allele at rs4691383 and the G allele at rs7667857 of PDGF-C gene were over-transmitted for NSCL/P (P<0.05). No interaction effect was observed between the three environmental exposure factors (history of smoking/passive smoking, folic acid supplementation, and long-term inhalation of harmful environmental gases) and the PDGF-C genotypes among NSCL/P (P>0.05). CONCLUSIONS: The rs4691383 and rs7667857 at PDGF-C gene are closely related to the occurrence of NSCL/P in Western Chinese population. However, the interaction between environmental exposure factors and PDGF-C genotypes is not obvious in the occurrence of NSCL/P.


Assuntos
Fenda Labial , Fissura Palatina , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Humanos , Linfocinas , Fator de Crescimento Derivado de Plaquetas , Polimorfismo de Nucleotídeo Único
16.
Crit Rev Anal Chem ; : 1-34, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32880479

RESUMO

Food safety and quality issues are becoming increasingly important and attract much attention, requiring the development of better analytical platforms. For example, high-resolution (especially Orbitrap) mass spectrometry simultaneously offers versatile functions such as targeted/non-targeted screening while providing qualitative and quantitative information on an almost unlimited number of analytes to facilitate routine analysis and even allows for official surveillance in the food field. This review covers the current state of Orbitrap mass spectrometry (OMS) usage in food analysis based on research reported in 2012-2019, particularly highlighting the technical aspects of OMS application and the achievement of OMS-based screening and quantitative analysis in the food field. The gained insights enhance our understanding of state-of-the-art high-resolution mass spectrometry and highlight the challenges and directions of future research.

17.
Spectrochim Acta A Mol Biomol Spectrosc ; 244: 118843, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32896709

RESUMO

Mixtures of ionic liquids (ILs) and molecular solvents can overcome the drawbacks (high viscosity, high polarity, and high cost) of pure ILs and extend their practical use. The structural and interaction properties of ILs form the bases for understanding their properties. In this work, the structural properties of the mixtures of an IL, 1-(2'-hydroxylethyl)-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C2OHMIM][Tf2N]), with chloroform, a molecular solvent of weak polarity, in various concentrations were analysed using Fourier transform infrared spectroscopy and density functional theory calculations. Excess spectra were used to analyse the infrared spectra. The IL forms a stable ion cluster-CDCl3 complex with CDCl3 in the concentration range investigated. In the ion cluster-CDCl3 complex, the hydrogen atom of CDCl3 forms hydrogen-bonds with the fluorine atoms of the anion. In addition, the chlorine atom of CDCl3 forms a halogen-bond with the oxygen atom of the anion. All the hydrogen and halogen-bonds identified between the [C2OHMIM][Tf2N] ion cluster and CDCl3 exhibit low strength, closed shells, and electrostatically dominant interactions.

18.
Chin Med J (Engl) ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32925290

RESUMO

BACKGROUND: Epithelial to mesenchymal transition (EMT) is strongly linked with tumor invasion and metastasis, which performs a vital role in carcinogenesis and cancer progression. Emerging evidence suggests that microRNAs (miRNAs) expression are closely associated to EMT by regulating targeted genes. MiR542 has been found to be involved in the EMT program and bound up with various cancers. However, the functions of miR542 and its underlying mechanism in glioblastoma multiforme (GBM) remain largely unknown. In the current study, we investigated the effect of astrocyte elevated gene-1 (AEG-1) on U251 cells aggressiveness, proliferation, apoptosis, and cell cycle. METHODS: The screening of targeted miRNAs was performed, as well as the functional roles and mechanisms of miR542 were explored. RESULTS: MiR542 was selected as the target because of the most significantly differential expression and this high level of expression negatively correlated with cell migration and proliferation, which suggested that miR542 could be a novel tumor suppressor. Moreover, we confirmed that AEG-1 was a direct targeted gene of miR542 by luciferase activity assay, reverse transcription-polymerase chain reaction, and immunoblotting analysis. Furthermore, miR542 suppressed the expression of AEG-1, which upgraded the level of E-cadherin and degraded Vimentin expression contributing to retraining EMT. CONCLUSION: The in vitro findings demonstrated that miR542 inhibited the migration and proliferation of U251 cells and suppressed EMT through targeting AEG-1, indicating that miR542 may be a potential anti-cancer target for GBM.

19.
Trends Mol Med ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32928643

RESUMO

As the major feature of pancreatic ductal adenocarcinoma (PDAC), desmoplastic stroma poses a significant obstacle for treatment. Recent studies revealed that connective tissue growth factor (CTGF) aggravates the fibrotic environment and drives cancer initiation and progression, thus suggesting CTGF as a novel target for PDAC treatment.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32928734

RESUMO

We determined in vivo efficacy and target PK/PD exposures of antofloxacin against S. pneumoniae and S. aureus in the murine pneumonia model. The mean plasma fAUC/MIC targets associated with stasis, 1-log10 and 2-log10 kill effects were 8.93, 19.2 and 48.1 for S. pneumoniae; whereas they were 30.5, 55.4 and 115.8 for S. aureus The fAUC/MIC targets in murine lung epithelial lining fluids (ELF) for the same endpoints were nearly 2-fold higher than those in plasma.

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