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1.
Artigo em Inglês | MEDLINE | ID: mdl-31584315

RESUMO

Epicardial adipose tissue (EAT) is associated with the pathogenesis of atrial fibrillation (AF). The role of local inflammation in persistent AF is unclear. The purpose of this study was to assess the relationship between regional interleukin-1ß (IL-1ß) and persistent AF. Thirty-seven persistent AF patients underwent coronary artery bypass grafting surgery were enrolled. Patients without a history of AF (n = 37), but received the same surgery matched by age, gender, and body mass index, were enrolled in the control group. EAT thickness was measured by echocardiography. We obtained blood and EAT samples at open-heart surgery. In each patient, serum and EAT levels of IL-1ß and adiponectin were measured. The EAT thickness in patients with persistent AF was significantly greater than that in the control group (5.6 ± 1.1 versus 5.0 ± 1.3 mm, P = 0.02). The mRNA level of IL-1ß was higher in persistent AF group than the control group (4.94 ± 1.69 versus 2.93 ± 0.91, P < 0.01). Adiponectin expression decreased in persistent AF patients (7.04 ± 2.21 versus 8.63 ± 2.95, P = 0.01). There were no significant differences in plasma levels of IL-1ß and adiponectin between the 2 groups. Multiple logistic regression analysis showed that IL-1ß was an independent risk factor of persistent AF. These findings suggested that regional IL-1ß in EAT was an independent risk factor of persistent AF, which may promote the persistence of AF.

2.
Am J Hematol ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591739

RESUMO

We conducted a prospective, multicenter study to evaluate the efficacy and safety of low-dose decitabine in adult patients with refractory immune thrombocytopenia. Adult patients who did not respond to, did not tolerate, or were unwilling to undergo splenectomy, with either a baseline platelet count less than 30 × 109 per L or the presence of bleeding symptoms and further need of ITP-specific treatments, were enrolled. Patients received decitabine at 3.5 mg/m2 intravenously for three consecutive days per cycle for three cycles with a 4-week interval between cycles. All patients were assessed every week during the first 12 weeks and at 4-week intervals thereafter. We screened 49 patients for eligibility. Four patients were excluded and 45 received decitabine. At the end of decitabine treatment, complete response was achieved in eight patients (17.78%) and partial response was achieved in 15 patients (33.33%). The median time to initial response was 28 days (range, 14-70 days). Furthermore, seven relapsed patients received decitabine retreatment and all showed platelet response, including one complete response and six partial response. Sustained response rates at 6, 12 and 18 months were 44.44% (20/45), 31.11% (14/45) and 20.0% (9/45), respectively. For responders, immune thrombocytopenia-related symptoms, fatigue, psychological health, fear, and overall quality of life were significantly improved. Adverse events were observed in 13 (28.89%) patients. No serious adverse events were recorded. In conclusion, low-dose decitabine is potentially effective and safe in the management of adults with refractory immune thrombocytopenia. This trial is registered with clinicaltrials.gov identifier: NCT01568333. This article is protected by copyright. All rights reserved.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31568595

RESUMO

BACKGROUND: In previous epidemiological study, the prevalence of atopic dermatitis (AD) was 12.94% among children aged 1-7ys by clinical diagnosis, whereas that was 4.76% and 3.51% using U.K., and Hanifin and Rajka diagnostic criteria. OBJECTIVE: We aimed to propose new diagnostic criteria for children, and evaluate its efficiency in different populations. METHODS: We screened atopic features and analyzed their correlation with AD using data from a previous study. A new set of diagnostic criteria for children in China were proposed and validated in 1,031 children in outpatient clinics, and 538 children in a birth cohort survey. Clinical diagnosis and atopic feature evaluation was performed face-to-face by dermatologists specialized in AD. Three criteria were compared for diagnostic efficiency using the clinical diagnosis as the reference. RESULTS: The new diagnostic criteria for children were based on (i) pruritus; (ii) "typical morphology and distribution" or "atypical morphology and distribution with xerosis"; and (iii) a chronic or chronically relapsing course. Compared to classical diagnostic criteria, the sensitivity of the new diagnostic criteria was significantly higher in the epidemiological survey and the clinical setting, especially obvious among mild and moderate AD. In the birth cohort, the new criteria showed similar sensitivity and specificity. CONCLUSION: The new criteria for children yielded higher sensitivity for the diagnosis of AD in the epidemiological survey and clinical setting, particularly for mild and moderate AD. Among the birth cohort with a complete medical history, three criteria showed similar sensitivity and specificity.

4.
Nat Biotechnol ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570897

RESUMO

The near-infrared-IIb (NIR-IIb) (1,500-1,700 nm) window is ideal for deep-tissue optical imaging in mammals, but lacks bright and biocompatible probes. Here, we developed biocompatible cubic-phase (α-phase) erbium-based rare-earth nanoparticles (ErNPs) exhibiting bright downconversion luminescence at ~1,600 nm for dynamic imaging of cancer immunotherapy in mice. We used ErNPs functionalized with cross-linked hydrophilic polymer layers attached to anti-PD-L1 (programmed cell death-1 ligand-1) antibody for molecular imaging of PD-L1 in a mouse model of colon cancer and achieved tumor-to-normal tissue signal ratios of ~40. The long luminescence lifetime of ErNPs (~4.6 ms) enabled simultaneous imaging of ErNPs and lead sulfide quantum dots emitting in the same ~1,600 nm window. In vivo NIR-IIb molecular imaging of PD-L1 and CD8 revealed cytotoxic T lymphocytes in the tumor microenvironment in response to immunotherapy, and altered CD8 signals in tumor and spleen due to immune activation. The cross-linked functionalization layer facilitated 90% ErNP excretion within 2 weeks without detectable toxicity in mice.

5.
J Cell Biochem ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31571264

RESUMO

Acute coronary syndrome (ACS) is characterized by atherosclerotic plaque rupture with a high incidence of recurrent ischemic events. Several microRNAs are found to be aberrantly expressed in atherosclerotic plaques. This study aims to investigate the effects of microRNA-9 (miR-9) on vulnerable atherosclerotic plaque and vascular remodeling in ACS and underlying mechanisms. Microarray-based gene expression profiling was used to identify differentially expressed genes related to ACS and regulatory miRNAs. Oxidized low-density lipoprotein (lectin-like) receptor 1 (OLR1) was identified to be aberrantly activated in ACS and regulated by miR-9. OLR1 was verified as a target gene of miR-9 by bioinformatics prediction and dual luciferase reporter gene assay. The atherosclerotic models were induced in ApoE-/- mice, in which the agomir or antagomir of miR-9, or small interfering RNA (siRNA) against OLR1 were separately introduced. Serum lipid levels and expression of vascular remodeling and inflammatory response-related factors were determined, respectively. On the basis of the obtained results, in the atherosclerosis mice treated with the agomir of miR-9 and siRNA against OLR1, the p38-mitogen-activated protein kinase (p38MAPK) pathway was inhibited; levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, tumor necrosis factor-α, interleukin-6, and vascular endothelial growth factor were reduced, but the high-density lipoprotein cholesterol level was increased, along with decreased vulnerable atherosclerotic plaque area and enhanced vascular remodeling. Taken together, these findings suggested an inhibitory role miR-9 acts in the formation of vulnerable atherosclerotic plaques in ACS mice, along with a promoted vascular remodeling, via a negative feedback regulation of OLR1-mediated p38MAPK pathway.

6.
EBioMedicine ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31590928

RESUMO

BACKGROUND: Oxidative stress and their effectors play critical roles in carcinogenesis and chemoresistance. However, the role of oxidative stress-related genes variants in biliary tract cancer (BTC) chemoresistance remains unknown. In this work, we aim to investigate oxidative stress-dependent molecular mechanisms underlying chemoresistance, and find potential biomarkers to predict chemotherapy response for BTC. METHODS: Sixty-six SNPs in 21 oxidative stress-related genes were genotyped and analyzed in 367 BTC patients. Immunoblot, immunohistochemical, immunofluorescent, quantitative PCR, chromatin immunoprecipitation analysis and study of animal xenograft models were performed to discover oxidative stress-related susceptibility genes underlying chemoresistance mechanism of BTC. FINDINGS: We found that 3 functional polymorphisms (CAT_rs769217, GPX4_rs4807542, and GSR_rs3779647), which were shown to affect their respective gene expression levels, modified the effect of chemotherapy on overall survival (OS). We then demonstrated that knockdown of GPX4, CAT, or GSR induced chemoresistance through elevation of ROS level and activation of Nrf2-ABCG2 pathway in BTC cell lines. Moreover, the association between Nrf2 expression and BTC prognosis is only found in patients who received chemotherapy. Knockdown of Nrf2 enhanced chemosensitivity or even eliminated postoperative recurrence in BTC xenograft mouse models. Importantly, upon chemotherapy treatment patients harboring high oxidative stress-related score received higher survival benefit from adjuvant chemotherapy compared with patients with low oxidative stress-related score. INTERPRETATION: The result of our study suggests, for the first time, that the oxidative stress-related score calculated by combining variations in CAT, GPX4, and GSR or Nrf2 expression could be used for predicting the chemosensitivity of BTC patients. FUND: This work was supported by the National Science Foundation of China, Foundation of Shanghai Shen Kang Hospital Development Center, and Shanghai Outstanding Academic Leaders Plan.

7.
Phys Rev E ; 100(2-1): 022317, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31574702

RESUMO

Although non-Markovian processes are considerably more complicated to analyze, real-world epidemics are likely non-Markovian, because the infection time is not always exponentially distributed. Here, we present analytic expressions of the epidemic threshold in a Weibull and a Gamma SIS epidemic on any network, where the infection time is Weibull, respectively, Gamma, but the recovery time is exponential. The theory is compared with precise simulations. The mean-field non-Markovian epidemic thresholds, both for a Weibull and Gamma infection time, are physically similar and interpreted via the occurrence time of an infection during a healthy period of each node in the graph. Our theory couples the type of a viral item, specified by a shape parameter of the Weibull or Gamma distribution, to its corresponding network-wide endemic spreading power, which is specified by the mean-field non-Markovian epidemic threshold in any network.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31585734

RESUMO

Hepatitis C virus (HCV) non-structural (NS) 5A protein is a multifunctional phosphoprotein. NS5A exists as hypo- and hyper-phosphorylated forms and the dynamic transitions between these two states are involved in the functions of NS5A. Hyperphosphorylation occurs primarily at six serine residues within the low complexity sequence I of NS5A. We previously showed that NS5A downregulates viral translation. In this study, we investigated the role of NS5A hyperphosphorylation in translation modulation. By analyzing the effects of phospho-ablative and phospho-mimetic mutants of the six serine residues on translation, we showed that NS5A hyperphospho-ablative mutation at all six serine residues can no longer downregulate viral translation. We then studied the effects of phospho-mutations at each of the six serine residues on translation. We found that phosphorylation of S222, S225, S235 is not involved in translation downregulation by NS5A. In contrast, NS5A with alanine mutations at S229 or S238 can no longer downregulate translation, whereas S229D or S238D mutations have no effect. Interestingly, S232D NS5A, but not S232A, abrogates translation downregulation by NS5A. Since dimerization of NS5A plays an important role in its functions, we also studied the effects of phospho-mutants of S229, S232, and S238 on dimerization in a protein-protein interaction assay. We showed that phopho-mimetic S229D or S238D mutations enhances NS5A dimerization, whereas the phospho-ablative mutations of these two residues have no effect. Neither phospho-ablative nor phopho-mimetic mutations of S232 affect dimerization. These results indicate that phosphorylation of NS5A at S229, S232, and S238 is involved in viral translation regulation and NS5A dimerization.

9.
Neurochem Res ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31531752

RESUMO

The hippocampus is critical for memory and emotion and both N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl- 4-isoxazolepropionic acid (AMPA) receptors are known to contribute for those processes. However, the underlying molecular mechanisms remain poorly understood. We have previously found that mice undergo memory decline upon dcf1 deletion through ES gene knockout. In the present study, a nervous system-specific dcf1 knockout (NKO) mouse was constructed, which was found to present severely damaged neuronal morphology. The damaged neurons caused structural abnormalities in dendritic spines and decreased synaptic density. Decreases in hippocampal NMDA and AMPA receptors of NKO mice lead to abnormal long term potentiation (LTP) at DG, with significantly decreased performance in the water maze, elevated- plus maze, open field and light and dark test. Investigation into the underlying molecular mechanisms revealed that dendritic cell factor 1 (Dcf1) contributes for memory and emotion by regulating NMDA and AMPA receptors. Our results broaden the understanding of synaptic plasticity's role in cognitive function, thereby expanding its known list of functions.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31471987

RESUMO

A 70-year-old man with recurrent symptomatic supraventricular tachycardia was referred for catheter ablation. Atrial activation was earliest at the His bundle region with HA longer than AH.

12.
Appl Opt ; 58(25): 6848-6853, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31503655

RESUMO

A sensing device composed of an eccentric core photonic quasi-crystal fiber based on surface plasmon resonance is designed using indium tin oxide (ITO) as the sensitive materials. The ITO film is deposited on the outside surface of the fiber to excite plasmonic interactions and facilitate refractive index (RI) detection. This eccentric core structure makes the evanescent field coupled effectively with analyte to achieve higher sensitivity. The influence of RI and structural parameters of different analytes on sensor performance was calculated by the finite-element method. In the analyte RI range between 1.33 and 1.39, the wavelength sensitivity reaches 21,100 nm/RIU, and the average sensitivity of 8750 nm/RIU is achieved at a resolution of 4.739×10-6 RIU. The sensor has large potential in the detection of unknown RI analytes in the near-infrared region.

13.
Appl Opt ; 58(23): 6308-6314, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503775

RESUMO

A bimetal-coated single-polarization photonic crystal fiber (PCF) filter based on surface plasmon resonance (SPR) with a liquid-filled structure is designed and calculated by the finite element method (FEM). The filter has many excellent properties. The y-polarized and x-polarized modes can simultaneously filter at 1310 nm and 1560 nm with unwanted losses 544.3 dB/cm and 147.3 dB/cm, respectively, corresponding to polarized losses as low as 12.3 dB/cm and 24.0 dB/cm. The filtering range can be tuned by adjusting the diameter of the outer air holes (d1), the diameter of the inner air holes (d2), and liquid refractive index n. The filtering ranges of x-polarization and y-polarization are 1550-1990 nm and 1310-1830 nm, respectively. The crosstalk (CT) values are 462.0 dB and -107.1 dB and corresponding available bandwidths are 224 nm and 504 nm at 1310 nm and 1560 nm, respectively.

14.
Appl Opt ; 58(18): 5082-5089, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31503829

RESUMO

A silicon trimer is explored to tailor unidirectional forward scattering at multiple wavelengths in the near-infrared region with low loss using theoretical calculations and numerical simulations, which leads to the dramatic enhancement in unidirectional forward scattering and suppression of backward scattering. The higher moments in the trimer can be properly excited and balanced by breaking the symmetry of the trimer. The generalized Kerker conditions at two different wavelengths can be achieved in the trimer to further improve the scattering directivity. Our results provide insights into future development of all-dielectric low-loss nanoantennas in the near-infrared region.

15.
Arch Toxicol ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501917

RESUMO

N,N-Dimethylformamide (DMF) is a widespread contaminant of leather factories and their surrounding environment. There is a lack of direct in vivo evidence supporting CYP2E1 as a primary enzyme responsible for DMF metabolism and hepatotoxicity. In this study, a novel Cyp2e1 knockout (KO) mouse model was generated and used to assess whether DMF metabolism and hepatotoxicity is CYP2E1 dependent using an acute toxicity protocol with a single dose of 1500 mg DMF/kg. An epidemiological study in 698 DMF-exposed workers and 188 non-DMF-exposed controls was conducted to investigate the associations between functional polymorphisms of CYP2E1 (rs6413432/rs2031920) and DMF metabolite (N-methylcarbmoylated-hemoglobin [NMHb]). We successfully established Cyp2e1 KO mice with evidence from DNA sequence analysis, which showed 1-bp insertion at 65 bp (C) site of Cyp2e1 Exon 1. In addition, western blot and in vivo pharmacokinetic study also showed a complete absence of CYP2E1 protein and a 92% and 88% reduction in CYP2E1 activity among males and females, respectively. DMF metabolism as evidenced by increased blood NMHb, and hepatotoxicity as evidenced by elevated liver/body weight ratio, activity of liver enzymes and massive liver necrosis were detected in wild-type (WT) mice but were completely abrogated in KO mice, strongly supporting a CYP2E1-dependent pattern of DMF metabolism and hepatotoxicity. Moreover, variant allele of CYP2E1-rs6413432 was also significantly associated with higher NMHb levels in DMF-exposed workers (P = 0.045). The increase of glucose-regulated protein 94 detected in WT mice but not in KO mice suggested CYP2E1-dependent endoplasmic reticulum stress may be a key mechanism underlying DMF-induced hepatotoxicity.

16.
Neuroreport ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31503203

RESUMO

Dendritic spines are divided into four subtypes, namely, Mushroom, Stubby, Thin, and Branched. The mushroom-shaped spines are related to learning and memory. Previous studies have shown that the dendritic cell factor 1 (Dcf1, a transmembrane protein) affects the memory process and regulates the development of dendritic spines by inhibiting the expression of lipocalin 2 (Lcn2, a member of the family containing over 20 small secreted proteins). However, the exact subtype of dendritic spines that are specifically affected by Dcf1 remains unknown. Here, we identified that deletion of Dcf1 leads to developmental defects in mushroom-shaped spines. We provide evidence for memory defects caused by Dcf1-knockout in mice. We discovered and report for the first time that Dcf1 affects the development of mushroom-shaped spines by inhibiting the expression of Lcn2. Further, we demonstrated that environmental enrichment can effectively stimulate Dcf1-knockout mice and rescue development defects in mushroom-shaped spines caused by Dcf1 deletion. Our results provide a novel direction for further studies on dendritic spine development and mechanisms associated with learning and memory.

17.
J Emerg Med ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31514988

RESUMO

BACKGROUND: Acute pain is the most common complaint in Emergency Department (ED) admissions, and options for analgesia are limited. Nitrous oxide/oxygen possesses many properties showing it may be an ideal analgesic in the ED. OBJECTIVES: The aim of this study is to evaluate the safety and analgesic effect of the fixed nitrous oxide/oxygen mixture for trauma patients in the ED. METHODS: We enrolled 60 patients in this double-blind, randomized study. The treatment group received conventional pain treatment plus a mixture of 65% nitrous oxide/oxygen. The control group received the conventional pain treatment plus oxygen. Primary outcome was the reduction in pain intensity at 5 and 15 min after the start of intervention. Secondary outcomes include adverse events, physiological parameters, and satisfaction from both patients and health care professionals. RESULTS: Initial pain scores for the nitrous oxide/oxygen group (6.0 [5.0-8.0]) and the oxygen group (6.75 [5.0-9.0]) were comparable (p = 0.57). The mean numerical rating scale scores at 5 min were 3.4 ± 1.8 and 7.0 ± 1.8 for nitrous oxide/oxygen and oxygen, respectively (p < 0.01). The mean pain intensity at 15 min in the treatment group was 3.0 ± 1.9, compared with 6.3 ± 2.2 in the control group (p < 0.01). Both patients' (8.0 [7.0-9.0] vs. 4.0 [2.0-6.0], p < 0.01) and physicians' (8.5 [8.0-9.0] vs. 4.0 [3.0-6.0], p < 0.01) satisfaction scores in the treatment group were significantly higher than the oxygen group. No serious adverse events were observed. CONCLUSIONS: This study gives supporting evidence for the safety and effectiveness of using self-administered nitrous oxide/oxygen mixture in the ED for moderate-to-severe traumatic pain.

18.
Am J Chin Med ; 47(6): 1193-1221, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31488038

RESUMO

Veronica is the largest genus in the flowering plant family Plantaginaceae and comprises approximately 500 species. The genus was formerly placed in the Scrophulariaceae family, some species of which have been used in traditional medicine for the treatment of influenza, respiratory diseases, hemoptysis, laryngopharyngitis, cough, hernia, cancer, edema, and wounds. This review comprehensively summarizes the current information on the traditional uses, phytochemistry, and pharmacology of the genus Veronica on the basis of articles published from 1970 to 2018. More than 260 compounds have been isolated, and chemotaxonomic investigations of Veronica have revealed that iridoid glucosides - including aucubin, catalpol, and 6-O-catalpol derivatives - are characteristic of this genus. Modern pharmacological studies and clinical practice have demonstrated that extracts or monomeric compounds from Veronica have several pharmacological actions, such as anti-inflammatory, anti-oxidative, anticancer, antibacterial, anti-angiogenic, antineurodegenerative, neuroprotective, and hepatoprotective effects both in vivo and in vitro.

19.
Cytokine ; 125: 154853, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31557634

RESUMO

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet count with heterogeneous bleeding manifestations. Severe bleeding in ITP is not completely related with low platelet count. Fcγ receptor (FcγR)-mediated platelet destruction is one of the major mechanisms of ITP. Interleukin-37 (IL-37) is a fundamental natural suppressor of innate immunity and inflammatory responses in several autoimmune diseases. However, the role of IL-37 in the pathogenesis of ITP is unknown. In the present study, we identified that IL-37 expression was elevated in ITP patients, which was correlated with platelet count and the severity of bleeding in ITP, indicating that IL-37 could be a candidate in evaluating disease severity of ITP. In the in vitro study, IL-37 initiated an anti-inflammatory effect on monocytes/macrophages from ITP patients by down-regulating the phosphorylation of MAPK, AKT, and NF-κB signaling pathways. Moreover, IL-37 restored the balance of activating and inhibitory FcγRs and decreased antibody-mediated platelet phagocytosis by monocytes/macrophages. Our findings suggest that IL-37 may be a promising indicator of the disease severity and supplementation of IL-37 may be therapeutically beneficial for ITP patients.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31557892

RESUMO

In this study, water levels observed at tide stations in the Bohai Sea, Yellow Sea, and East China Sea during Typhoons 7203 and 8509 were assimilated into a numerical assimilation storm surge model combined with regularization technique to study the wind-stress drag coefficient. The Tikhonov regularization technique with different regularization parameters was tested during the assimilation. Using the regularization technique, the storm surge elevations were successfully simulated in the whole sea areas during Typhoons 7203 and 8509. The storm surge elevations calculated with the regularization technique and the elevations calculated with independent point method were separately compared with the observed data. Comparison results demonstrated that the former was closer to the observed data. The regularization technique had the best performance when the regularization parameter was 100. The spatial distribution of the inverted drag coefficient, storm surge elevations, and the wind fields during both typhoons were presented. Simulated results indicated that the change of drag coefficient is more significant in the coastal regions of the Bohai Sea and north of the Yellow Sea. Further analysis showed that the rising water elevation in the Bohai Sea is mostly attributed to the influence of onshore winds, and the negative storm surge in the South Yellow Sea is mainly caused by offshore winds.

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