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1.
Sci Total Environ ; 792: 148363, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34465051

RESUMO

The alpine meadow in the Qinghai-Tibet Plateau has been seriously degraded due to human activities and climate change in recent decades. Understanding the changes of the soil microbial community in response to the degradation process helps reveal the mechanism underlying the degradation process of alpine meadows. We surveyed and analyzed changes of the vegetation, soil physicochemical properties, and soil microbial community in three degradation levels, namely, non-degradation (ND), moderate degradation (MD), and severe degradation (SD), of the alpine meadows in the northeastern Qinghai-Tibet Plateau. We found that as the level of degradation increased, plant cover, plant density (PD), above-ground biomass (AGB), plant Shannon-Wiener index (PS), soil water content (SWC), soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), total potassium (TK), available nitrogen (AN), available phosphorus (AP), and available potassium (AK) decreased significantly, while the soil pH increased from 7.20 to 8.57. Alpine meadow degradation significantly changed the composition of soil bacterial and fungal communities but had no significant impact on the diversity of the microbial communities. Functional predictions indicated that meadow degradation increased the relative abundances of aerobic_chemoheterotrophy, undefined_saprotroph, and plant_pathogen, likely increasing the risk of plant diseases. Redundancy analysis revealed that in ND, the soil microbial community was mainly regulated by PS, PH, PD, SWC, and soil pH. In MD, the soil microbial community was regulated by the soil's available nutrients and SOC. In SD, the soil microbial community was not only regulated by the soil's available nutrients but also influenced by plant characteristics. These results indicate that during alpine meadow degradation, while the changes in the plants and soil environmental factors both affect the composition of the soil microbial community, the influence of soil factors is greater. The soil's available nutrients are the main driving factors regulating the change in the soil microbial community's composition alongside degradation levels.


Assuntos
Microbiota , Solo , Carbono/análise , Pradaria , Humanos , Nutrientes , Microbiologia do Solo , Tibet
2.
Materials (Basel) ; 14(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361428

RESUMO

To ensure safety and prevent failure of engineering equipment throughout its lifespan, the concept of 'Safety Design' is proposed, which covers all the cradle-to-grave phases of engineering equipment, considers at least ten essential factors of failure causes, and conducts root cause analysis at three different scales, in order to proactively control the safety risks before the occurrence of failure rather than passively conduct the remedial measures after failure. Herein, in order to demonstrate how to implement this effective and efficient concept in engineering practice, a case study of failure analysis and prevention is addressed on the extraction column in the production line for methyl methacrylate. Based on the analysis results, the causes were finally determined to be all derived from the stages before operation, including inappropriate design, limited quality inspection of fabrication and installation. Pertinent countermeasures were then proposed from the 'Safety Design' point of view, which would not only solve the failure problem for this sole equipment but also contribute to safety risk control of other engineering equipment before operation.

3.
Anal Chim Acta ; 1174: 338711, 2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34247742

RESUMO

Surface-enhanced Raman scattering (SERS) has attracted much attention with its powerful trace detection and analysis capabilities, especially biological and environmental molecules. However, building a protein SERS detection platform based on semiconductor devices is a huge challenge. Herein, through the synergy of NH3 and nickel foam, a large-sized semiconductor tungsten oxide hydrate platform (WOHP) was synthesized. The crystal plane of a single WOHP particle is larger than the excitation spot. As a SERS substrate, WOHP can make full use of the excitation light without destroying the structure during the protein molecules detection process. Through the synergy of WOHP and Au NPs, the enhancement factor is 1.5 × 104. Raman peaks of WOHP can be used as references for the detection of typical protein cytochrome C (Cyt C). As the Cyt C concentration decreases, the ICyt C/IWOHP ratio decreases, and the signal can still be obtained when the concentration is as low as 5 × 10-9 mol L-1. More importantly, the method does not affect the catalytic activity of Cyt C and can be applied to the detection of Cyt C concentration in serum.


Assuntos
Ouro , Nanopartículas Metálicas , Citocromos c , Óxidos , Análise Espectral Raman , Tungstênio
4.
Front Cell Infect Microbiol ; 11: 672221, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34222044

RESUMO

Objectives: To compare the safety, immunogenicity, and immune persistence of hepatitis A (HA) vaccines between HBs-Ag-positive and -negative participants. Method: 9000 participants were enrolled in the phase IV study of live attenuated HA (HA-L) or inactivated HA (HA-I) vaccines. The HBs-Ag-positive subjects were detected and became an independent observation group. Adverse reactions (ARs), geometric mean concentrations (GMCs) and seroconversion rates (SRs) of the vaccines were analyzed at five time points until three years after vaccination. Results: 120 HBs-Ag-positive subjects were screened out, only 1 participant had grade 1 experienced ARs after HA-L injection. Except the time point of two years, the SRs of HBs-Ag-positive group were 100% for both vaccines. The GMCs were not statistically different between HBs-Ag-positive and -negative groups after the HA-L vaccination. The logarithmically transformed GMCs for HBs-Ag-positive and -negative groups were 3.21 mIU/mL (95% CI, 2.03-4.39 mIU/mL) and 2.95 mIU/mL (95% CI, 2.88-3.02 mIU/mL) 28 days after the HA-L vaccination, respectively. Conclusions: Both HA-L and HA-I vaccines were safe for HBs-Ag-positive participants and may provide an excellent long-term protection against HAV in this study. The results indicated that people positive or negative for HBs-Ag can receive both HA-L and HA-I vaccines (ClinicalTrials.gov number, NCT02601040).


Assuntos
Vacinas contra Hepatite A , Prata , Vacinas contra Hepatite A/efeitos adversos , Anticorpos Anti-Hepatite B , Humanos , Imunização Secundária , Estudos Retrospectivos
5.
J Hypertens ; 39(10): 2122-2123, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34285151
6.
J Nat Prod ; 84(6): 1816-1822, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34043363

RESUMO

Secoisolariciresinol diglucoside (SDG) is the principal lignan of flaxseed and precursor of its aglycone, secoisolariciresinol (SECO), and the mammalian lignans enterolactone (EL) and enterodiol (ED), the putative bioactive forms of oral administration of SDG. SDG is present in the seed hull as an ester-linked polymer. Although extraction and purification of SDG monomer is costly, the use of naturally occurring SDG in polymer form may offer a more economical approach for delivery of this precursor. The extent of SDG release from the polymer and subsequent bioavailability of SDG metabolites are unknown. To understand the relative bioavailability of SDG polymer, this study examined the comparative bioavailability of enriched SDG and SDG polymer in rats after a single oral SDG equivalent dose (40 mg/kg). A validated LC-MS/MS method quantified SDG and its metabolites in rat plasma following serial blood collections. SDG remained undetectable in rat plasma samples. Unconjugated SECO was detected in plasma after 0.25 h. Unconjugated ED was observed after 8 h (3.4 ± 3.3 ng/mL) and 12 h (6.2 ± 3.3 ng/mL) for enriched SDG and SDG polymer, respectively. Total (conjugated and unconjugated) ED and EL resulting from enriched SDG and SDG polymer reached similar maximal concentrations between 11 and 12 h and demonstrated similar total body exposures (AUC values). These data suggest a similar pharmacokinetic profile between the enriched and polymer form of SDG, providing support for the use of SDG polymer as a more economical precursor for SECO, ED, and EL in applications of chronic disease management.

7.
Front Endocrinol (Lausanne) ; 12: 619586, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815278

RESUMO

Background: Hyperglycemia is associated with an increased risk of developing atrial fibrillation (AF) and atrial flutter (AFL). Sodium-glucose transporter 2 inhibitors (SGLT2i) have been reported to prevent AF/AFL in some studies, but not others. Therefore, a meta-analysis was performed to investigate whether SGLT2i use is associated with lower risks of AF/AFL. Methods: PubMed, Scopus, Web of Science, Cochrane library databases were searched for randomized placebo-controlled trials comparing SGLT2i and placebo. Results: A total of 33 trials involving 66,685 patients were included. The serious adverse events (SAEs) of AF/AFL occurrence were significantly lower in the SGLT2i group than the placebo group (0.96% vs. 1.19%; RR 0.83; 95% CI 0.71-0.96; P = 0.01; I2 25.5%). Similarly, the SAEs of AF occurrence was significantly lower in the SGLT2i group (0.82% vs. 1.06%; RR 0.81; 95% CI 0.69-0.95; P = 0.01; I2 10.2%). The subgroup analysis showed that the reduction in AF/AFL was significant only for dapagliflozin (1.02% vs. 1.49%; RR 0.73; 95% CI 0.59-0.89; P = 0.002; I2 0%), but not for canagliflozin (1.00% vs 1.08%; RR 0.83; 95% CI 0.62-1.12; P = 0.23; I2 0%), empagliflozin (0.88% vs 0.70%; RR 1.20; 95% CI 0.76-1.90; P = 0.43; I2 0%), ertugliflozin (1.01% vs 0.96%; RR 1.08; 95% CI 0.66-1.75; P = 0.76; I2 0%), and sotagliflozin (0.16% vs 0.10%; RR 1.09; 95% CI 0.13-8.86; P = 0.93; I2 0%). Conclusions: SGLT2i use is associated with a 19.33% lower SAEs of AF/AFL compared with the placebo. Dapagliflozin users had the lowest SAEs of AF/AFL incidence. Further studies are needed to determine whether canagliflozin, empagliflozin, ertugliflozin, and sotagliflozin similarly exert protective effects against AF/AFL development.

8.
J Med Internet Res ; 23(4): e24996, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33871375

RESUMO

BACKGROUND: With the prevalence of cardiovascular diseases increasing worldwide, early prediction and accurate assessment of heart failure (HF) risk are crucial to meet the clinical demand. OBJECTIVE: Our study objective was to develop machine learning (ML) models based on real-world electronic health records to predict 1-year in-hospital mortality, use of positive inotropic agents, and 1-year all-cause readmission rate. METHODS: For this single-center study, we recruited patients with newly diagnosed HF hospitalized between December 2010 and August 2018 at the First Affiliated Hospital of Dalian Medical University (Liaoning Province, China). The models were constructed for a population set (90:10 split of data set into training and test sets) using 79 variables during the first hospitalization. Logistic regression, support vector machine, artificial neural network, random forest, and extreme gradient boosting models were investigated for outcome predictions. RESULTS: Of the 13,602 patients with HF enrolled in the study, 537 (3.95%) died within 1 year and 2779 patients (20.43%) had a history of use of positive inotropic agents. ML algorithms improved the performance of predictive models for 1-year in-hospital mortality (areas under the curve [AUCs] 0.92-1.00), use of positive inotropic medication (AUCs 0.85-0.96), and 1-year readmission rates (AUCs 0.63-0.96). A decision tree of mortality risk was created and stratified by single variables at levels of high-sensitivity cardiac troponin I (<0.068 µg/L), followed by percentage of lymphocytes (<14.688%) and neutrophil count (4.870×109/L). CONCLUSIONS: ML techniques based on a large scale of clinical variables can improve outcome predictions for patients with HF. The mortality decision tree may contribute to guiding better clinical risk assessment and decision making.


Assuntos
Registros Eletrônicos de Saúde , Insuficiência Cardíaca , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Aprendizado de Máquina , Prognóstico , Estudos Retrospectivos
9.
Hum Vaccin Immunother ; 17(8): 2560-2567, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-33848232

RESUMO

The switch from using only trivalent oral polio vaccine (tOPV) to sequential schedules combining inactivated poliovirus vaccine (IPV) and bivalent oral polio vaccine (bOPV) for polio vaccination will cause changes to mucosal immunity against polio in infants, which plays an important role in preventing the poliovirus spread. Here, we analyzed mucosal immunity against poliovirus in the intestine during different sequential vaccination schedules. We conducted clinical trials in Guangxi Province, China on 1,200 2-month-old infants who were randomly assigned to one of three vaccination schedule groups: IPV-bOPV-bOPV, IPV-IPV-tOPV, and IPV-IPV-bOPV, with vaccine doses administered at 8, 12, and 16 weeks of age. Stool samples were collected from 10% of participants in each group before administration of the second vaccine doses and at 1, 2, and 4 weeks after the administrations of the second and third vaccine doses. Immunoglobulin A (IgA) in the stool samples was measured to analyze the mucosal immune response in the intestine. Because of the absence of poliovirus type 2 in bOPV, the vaccination schedule of IPV-IPV-bOPV did not sufficiently raise intestinal mucosal immunity against poliovirus type 2, although some cross-immunity was seen. The level of intestinal mucosal immunity was related to shedding status; shedders could produce intestinal mucosa IgA more quickly. The intestinal mucosal immunity level was not related to serum neutralizing antibody level. In the combined sequential vaccination schedule of IPV and bOPV, the risk of circulating vaccine-derived poliovirus type 2 (cVDPV2) may be increased owing to insufficient intestinal mucosal immunity against poliovirus type 2.


Assuntos
Poliomielite , Poliovirus , Anticorpos Antivirais , China , Humanos , Imunidade nas Mucosas , Esquemas de Imunização , Lactente , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado , Vacina Antipólio Oral
10.
Int Heart J ; 62(2): 312-319, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33678799

RESUMO

This study aims to evaluate the incidence of ischemic stroke or transient ischemic attack (TIA) based on CHA2DS2-VASc scores in non-AF Chinese patients with sinus rhythm.We used health check-up data of 101,510 participants from the Kailuan Cohort Study. Participants' risk levels were defined by their CHA2DS2-VASc scores (range 0-3): Men with scores of 0, 1, or ≥ 2 and women with scores of 1, 2, or ≥ 3 were considered at low, intermediate, or high risk, respectively. Cox proportional hazards model was used to assess the association between the CHA2DS2-VASc-determined risk and the incidence of ischemic stroke/TIA.The mean 7.5 year follow-up examination revealed 2968 ischemic strokes/TIA events. The incidence rates for ischemic stroke/TIA events in men and women were 3.8% and 1.5%, respectively. The incidence of ischemic stroke/TIA increased with elevated predicted risks based on CHA2DS2-VASc scores in men: 2.2% for low-risk, 4.1% for intermediate-risk, and 7.8% for high-risk groups (P < 0.001 for trend). The incidences of ischemic stroke/TIA also increased with elevated predicted risks in women: 0.8% for low-risk, 2.1% for intermediate-risk, and 5.0% for high-risk groups (P < 0.001 for trend). Compared with low-risk group, the crude hazard ratio (95% confidence interval) of ischemic stroke/TIA for men in moderate- and high-risk groups were 1.96 (1.79-2.14; P < 0.001) and 4.18 (3.81-4.57; P < 0.001). Similar findings were observed in women.Risks of ischemic stroke/TIA events was high, particularly among those with high CHA2DS2-VASc scores.


Assuntos
Fibrilação Atrial/complicações , Isquemia Encefálica/epidemiologia , Frequência Cardíaca/fisiologia , Ataque Isquêmico Transitório/epidemiologia , Medição de Risco/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/etiologia , China/epidemiologia , Feminino , Humanos , Incidência , Ataque Isquêmico Transitório/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
11.
Hypertension ; 76(6): 1856-1867, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33175633

RESUMO

Hypertension is a risk factor of atrial fibrillation (AF), and a certain number of patients with hypertension were found with an enlarged left atrium. Platelet activation is found in patients with hypertension or pressure overload/Ang II (angiotensin II)-induced hypertensive animal models and contribute to ventricular fibrosis. Whether hypertension-induced atrial fibrosis is mediated by platelets remains unknown. Our previous experimental data showed that platelet-derived TGF-ß1 (transforming growth factor-ß1) was reduced in patients with hypertensive AF. The present study is to investigate whether platelet-derived TGF-ß1 promotes Ang II-induced atrial fibrosis and AF. Platelet activation and atrial platelet accumulation were measured in sinus rhythm controls, normotensive AF, and patients with hypertensive AF. Ang II (1500 ng/kg per minute, 3 weeks) infused mice with pharmacological (clopidogrel) and genetic platelet inhibition (TGF-ß1 deletion in platelets) were used. Platelet activation, atrial structural remodeling, atrial electrical transmission, AF inducibility, inflammation, and fibrosis were measured in mice. We found that circulating platelets were activated in patients with hypertensive AF. A large amount of platelet was accumulated in the atriums of patients with hypertensive AF. Both clopidogrel treatment and platelet-specific deletion of TGF-ß1 attenuated Ang II-induced structural remodeling, atrial electrical transmission, AF inducibility, as well as atrial inflammation and fibrosis than mice without interventions. Furthermore, clopidogrel blocked atrial platelet accumulation and platelet-fibroblast conjugation. Platelets promoted atrial fibroblast differentiation in cell culture. Profibrotic actions of platelets are largely via activation of atrial fibroblasts by releasing TGF-ß1 and inducing platelet-fibroblast conjugation, and platelet inhibition is sufficient to inhibit atrial fibrosis and AF inducibility.


Assuntos
Fibrilação Atrial/fisiopatologia , Plaquetas/fisiologia , Fibroblastos/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Angiotensina II , Animais , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/metabolismo , Remodelamento Atrial , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Clopidogrel/administração & dosagem , Fibroblastos/efeitos dos fármacos , Humanos , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Ativação Plaquetária/fisiologia , Inibidores da Agregação Plaquetária/administração & dosagem , Fator de Crescimento Transformador beta1/genética
12.
Front Cell Dev Biol ; 8: 592048, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195259

RESUMO

Macrophage polarization and inflammation are key factors for the onset and progression of atherosclerosis. The immunoproteasome complex consists of three inducible catalytic subunits (LMP2, LMP10, and LMP7) that play a critical role in the regulation of these risk factors. We recently demonstrated that the LMP7 subunit promotes diet-induced atherosclerosis via inhibition of MERTK-mediated efferocytosis. Here, we explored the role of another subunit of LMP10 in the disease process, using ApoE knockout (ko) mice fed on an atherogenic diet (ATD) containing 0.5% cholesterol and 20% fat for 8 weeks as an in vivo atherosclerosis model. We observed that ATD significantly upregulated LMP10 expression in aortic lesions, which were primarily co-localized with plaque macrophages. Conversely, deletion of LMP10 markedly attenuated atherosclerotic lesion area, CD68+ macrophage accumulation, and necrotic core expansion in the plaques, but did not change plasma metabolic parameters, lesional SM22α+ smooth muscle cells, or collagen content. Myeloid-specific deletion of LMP10 by bone marrow transplantation resulted in similar phenotypes. Furthermore, deletion of LMP10 remarkably reduced aortic macrophage infiltration and increased M2/M1 ratio, accompanied by decreased expression of pro-inflammatory M1 cytokines (MCP-1, IL-1, and IL-6) and increased expression of anti-inflammatory M2 cytokines (IL-4 and IL-10). In addition, we confirmed in cultured macrophages that LMP10 deletion blunted macrophage polarization and inflammation during ox-LDL-induced foam cell formation in vitro, which was associated with decreased IκBα degradation and NF-κB activation. Our results show that the immunoproteasome subunit LMP10 promoted diet-induced atherosclerosis in ApoE ko mice possibly through regulation of NF-κB-mediated macrophage polarization and inflammation. Targeting LMP10 may represent a new therapeutic approach for atherosclerosis.

13.
Int J Chron Obstruct Pulmon Dis ; 15: 2561-2572, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116473

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible expiratory airflow obstruction, and its chronic course is worsened by recurrent acute exacerbations. Our previous microarray assay identified microRNA (miR)-301a-5p as being associated with progression of acute exacerbation of COPD (AE-COPD); however, the mechanism underlying COPD pathogenesis remains unknown. Methods: Samples of serum and peripheral blood mononuclear cells (PBMCs) were isolated from healthy control subjects and patients with stable COPD (R-COPD) or with an acute exacerbation of COPD (AE-COPD). Human HULEC-5a and human bronchial epithelial (HBE) cells were transfected with methyl-CpG-binding domain protein 2 (MBD2), sh-MBD2, miR-301a-5p mimics or an inhibitor, and then stimulated with cigarette smoke extract (CSE). Conditioned medium co-culture assays were performed by adding the supernatant of medium derived from HULEC-5a cells transfected with miR-301a-5p mimics or inhibitor into wells containing si-c-x-c motif chemokine receptor 4 (CXCR4)-transfected-lung fibroblasts or human leukemic THP-1 cell line macrophages. Transwell assays were performed to analyze cell migration. Results: Our analysis of clinical samples showed that decreased miR-301a-5p levels in patients with AE-COPD were positively correlated with levels of MBD2 expression, but negatively correlated with levels of chemokine ligand C-X-C motif chemokine ligand 12 (CXCL12) expression. MBD2 overexpression significantly promoted miR-301a-5p production, but suppressed CXCL12 production in HULEC-5a and HBE cells. CXCL12 was confirmed to be a direct target of miR-301a-5p. CXCR4 knockdown significantly enhanced the suppressive effect of miR-301a-5p mimics and attenuated the promotional effects of the miR-301a-5p inhibitor on the migration of circulating fibroblasts and macrophages, as well as the expression levels of phospho-mitogen-activated protein kinase (p-MEK) and phospho-protein kinase B (p-AKT). Conclusion: In summary, the MBD2/miR-301a-5p/CXCL12/CXCR4 pathway was shown to affect the migration of lung fibroblasts and monocyte-derived macrophages, which may play an important role during COPD exacerbations.


Assuntos
MicroRNAs , Doença Pulmonar Obstrutiva Crônica , Quimiocina CXCL12/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Leucócitos Mononucleares/metabolismo , Pulmão/metabolismo , MicroRNAs/genética , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/genética , Receptores CXCR4/genética , Transdução de Sinais
14.
Inorg Chem ; 59(19): 14229-14235, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32916047

RESUMO

Optical thermometry has attracted great interest owing to its noncontact and fast responsive properties in practical applications. However, some sensing errors may occur in many optical ratiometric thermometers due to the overlap of emission peaks, suggesting the necessity of developing excellent luminescent materials. Here, we report the fabrication and characterization of Bi4Ti3O12:Yb/Ho for ratiometric thermometry. Bismuth titanate was selected as the matrix due to its low phonon energy, high machinability, and satisfactory thermal stability. The temperature sensing was constructed on the intensity ratio of the two upconversion emission bands with wide separation in Bi4Ti3O12:Yb/Ho under 980 nm excitation. The wide separation endows the materials with high signal discrimination for temperature detection. The developed materials were characterized in terms of crystal structure, reflectance, and emission spectra for thermometry application. The maximum relative sensitivity was shown to be as high as 2.11% K-1. More importantly, an optical fiber thermometry was developed based on the fabricated microcrystals, which can find its potential applications in harsh environments.

15.
Expert Rev Clin Pharmacol ; 13(9): 957-975, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32746653

RESUMO

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has spread globally since it outbroke in December 2019. The urgent pandemic presents an unprecedented challenge to develop and identify effective medication therapy strategies to combat the COVID-19. AREAS COVERED: Here, we summarized and evaluated the current treatment drugs and regimens, and put forward the treatment recommendations, including using the potential repurposed or experimental drugs against COVID-19, e.g. chloroquine (CQ), hydroxychloroquine (HCQ), lopinavir/ritonavir (LPV/r), remdesivir (RDV), and favipiravir (FPV). We also analyzed the specific drugs and vaccines against SARS-CoV-2 ongoing development and formulated the comprehensive treatment regimens based on condition of patients, diseases and drugs as well as concomitant medications. EXPERT OPINION: No drugs and vaccines have been proven to be particularly effective against SARS-CoV-2 up to now. The recommended comprehensive medication therapy strategies have already displayed favorable effect in the fight against COVID-19. Research should be focused on the development of anti-SARS-CoV-2 drugs and vaccines based on high-quality clinical trial evidence, treatment guidelines and expert consensus.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Vacinas Virais , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , COVID-19 , Vacinas contra COVID-19 , Infecções por Coronavirus/epidemiologia , Saúde Global , Pneumonia Viral/epidemiologia , SARS-CoV-2
16.
Chemistry ; 26(51): 11695-11700, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32648611

RESUMO

In this work, well-defined two-dimensional metallacycles have been successfully employed for the well-controlled self-assembly of gold nanoparticles (AuNPs) into discrete clusters such as dimers, trimers, tetramers, pentamers and even hexamers at the water-oil interface for the first time. Furthermore, the modular construction of metallacycle molecules allows precise control of spacing between the gold nanoparticles. Interestingly, it was found that interparticle spacing below 5 nm created by molecular metallacycles in the resultant discrete gold nanoparticle clusters led to a strong plasmon coupling, thus inducing great field enhancement inside the gap between the NPs. More importantly, different discrete clusters with precise interparticle spacing provide a well-defined system for studying the hot-spot phenomenon in surface-enhanced Raman scattering (SERS); this revealed that the SERS effects were closely related to the interparticle spacing.

17.
Medicine (Baltimore) ; 99(28): e21013, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664106

RESUMO

Autism spectrum disorder (ASD) is a serious nervous system disease, and the cause is not known. Sialic acid (SA) is an indispensable nutrient for early brain development. In previous study, it was found that the SA level of ASD group was lower than that of control group. However, the reason for this has not well explained. A case-control study was conducted to understand the association between the SA synthase enzyme regulatory gene and ASD. The study sample included 65 ASD children and 64 healthy children. The levels of the GNE gene were measured, which encodes UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE), a key enzyme in SA biosynthesis. The symptom severity, intelligence development level, and behavioral performance of ASD children were estimated. There was a significant difference in the levels of GNE between the ASD and control groups (t = 2.028, P = .045). Moreover, the levels of GNE were negatively related to stereotypical behaviors according to the Autism Diagnostic Observation Schedule (ADOS) assessment (r = -0.386, P = .039). However, there is no the correlation between the levels of GNE and autistic severity. As evaluated through the Social Responsiveness Scale (SRS), the levels of GNE were negatively associated with autistic mannerisms scores, social cognition scores and SRS total scores in the children with ASD (r = -0.314, P = .020). These results indicate that the GNE gene may be associated with autism spectrum disorder, and it is also related to autistic behavioral performance, such as stereotypical behaviors, autistic mannerisms, and social cognition ability. Our data suggest that future studies to explore the causal relationship between GNE and the etiology of ASD may be needed.


Assuntos
Transtorno do Espectro Autista/genética , Transtornos do Comportamento Infantil/genética , Complexos Multienzimáticos/genética , Transtorno do Espectro Autista/complicações , Estudos de Casos e Controles , Transtornos do Comportamento Infantil/complicações , Pré-Escolar , Feminino , Humanos , Masculino , Fenótipo
18.
NPJ Vaccines ; 5: 47, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32566258

RESUMO

The impact of intestinal microbiota on mucosal antibody response to the polio vaccine is poorly understood. We examined changes in vaccine-induced intestinal mucosal immunity to poliovirus by measuring the immunoglobulin A (IgA) antibody levels in stool samples collected from 107 infants in China, and the samples were collected 14 days after different sequential vaccinations combining inactivated polio vaccine (IPV) with oral poliovirus vaccine (OPV). Gut microbiota were identified using 16S ribosomal RNA sequencing 28 days before, 14 days before, and at the last dose of OPV. Vaccine-induced type 2-specific mucosal IgA showed a decrease after switching from trivalent to bivalent OPV (bOPV) (positive rate of polio type 2-specific mucosal IgA, 16.7%, 11.8%, and 45.9% for IPV + 2bOPV, 2IPV + bOPV, and 2IPV + trivalent OPV groups, respectively). The composition of the gut microbiome was significantly different, a higher abundance of Firmicutes and a lower abundance of Actinobacteria were observed in IgA-negative infant (n = 66) compared with IgA-positive infants (n = 39), and the gut microbiota were more diverse in IgA-negative infants on the day of OPV inoculation. The abundance of Clostridia was concomitant with a significantly lower conversion rate of mucosal IgA responses to the polio vaccine. The composition of the gut microbiome may affect the intestinal mucosal IgA response to the polio vaccine.

19.
Am J Physiol Heart Circ Physiol ; 319(1): H133-H143, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32469636

RESUMO

In clinical studies, platelet aggregation and risk of thrombosis are increased in patients after doxorubicin treatment. However, the exact role of doxorubicin in platelet functions and thrombus formation in vivo remain unclear. The present study is to investigate the role of doxorubicin in platelet function in relation to thrombus formation and vascular toxicity, as well as the efficacy of antiplatelet therapy. Mice were treated with doxorubicin or vehicle (5 mg/kg iv, 4 wk), and the following parameters were determined: platelet count and size, platelet surface adhesive receptors by flow cytometry, density of granules by electron microscopy, platelet aggregation and degranulation at resting or agonist-stimulated state, platelet adhesion on fibrinogen or endothelial cells, and thrombus formation on collagen matrix. The efficacy of clopidogrel (15 mg·kg-1·day-1, followed by 5 mg·kg-1·day-1) on doxorubicin-induced changes in the aforementioned parameters as well as vascular injury were also determined. Whereas platelet count and size were similar between doxorubicin-treated and vehicle-treated mice, doxorubicin promoted thrombus formation evidenced by greater platelet aggregation, degranulation, and adhesion to endothelial cells evoked by agonists. Clopidogrel treatment attenuated the enhanced platelet activity and thrombus formation by doxorubicin, as well as vascular platelet infiltration and reactive oxygen species generation. Collectively, this study demonstrates that platelet functions are enhanced after long-term doxorubicin administration, which leads to thrombus formation and vascular toxicity, and that doxorubicin-induced changes in the functionality of platelets can be effectively inhibited by antiplatelet drugs.NEW & NOTEWORTHY Doxorubicin therapy in mice (antitumor dosage) markedly enhanced platelet functions measured as agonist-induced platelet aggregation, degranulation, and adhesion to endothelial cells, actions leading to thrombus formation and thrombosis-independent vascular injury. Clopidogrel treatment ameliorated thrombus formation and vascular toxicity induced by doxorubicin via inhibiting platelet activity.


Assuntos
Antineoplásicos/toxicidade , Plaquetas/efeitos dos fármacos , Doxorrubicina/toxicidade , Endotélio Vascular/efeitos dos fármacos , Trombose/etiologia , Animais , Antineoplásicos/farmacologia , Plaquetas/fisiologia , Células Cultivadas , Doxorrubicina/farmacologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Agregação Plaquetária
20.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(3): 319-323, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32385996

RESUMO

OBJECTIVE: To observe the relationship between pulmonary artery systolic pressure (PASP) and acute renal injury (AKI) and prognosis after cardiopulmonary bypass (CPB) heart surgery. METHODS: The clinical data of 9 860 patients who underwent CPB heart surgery in Beijing Anzhen Hospital from January 1st, 2015 to December 31st, 2016 were analyzed retrospectively. The patients were divided into two groups according to whether AKI occurred after operation. The clinical data were obtained from hospital information system (HIS) and DoCare including general information, types of operation, preoperative complication, ejection fraction, serum creatinine (SCr), PASP, intraoperative CPB duration, aortic occlusion duration, fluid balance, blood products and drug usage, postoperative mechanical ventilation duration, length of intensive care unit (ICU) and hospital stay, and perioperative central venous pressure (CVP). Multivariate Logistic regression analysis was used to screen the risk factors of AKI after operation. According to the preoperative PASP level, the patients were divided into ≥ 60 mmHg (1 mmHg = 0.133 kPa) group and < 60 mmHg group, and the incidence of AKI and prognosis after operation were compared between the two groups. All patients were followed up by telephone after discharge, and they were divided into survival group and death group according to the follow-up results, and the clinical data were compared between the two groups. Multivariate Cox regression analysis was used to screen the risk factors of long-term prognosis. Kaplan-Meier survival curve was used to analyze the long-term prognosis of two groups with different preoperative PASP levels. RESULTS: 6 285 patients were enrolled in the final analysis. (1) Among the 6 285 patients, 2 592 patients (41.2%) suffered from AKI after operation, of whom 1 697 (65.5%) were stage 1 according to Kidney Disease: Improving Global Outcomes (KDIGO), which was the main type of AKI. Univariate analysis showed that age, preoperative ejection fraction, SCr, PASP, coronary heart disease, hypertension, diabetes, intraoperative CPB duration, aortic occlusion duration, fluid balance, red blood cell input and norepinephrine, dopamine, epinephrine dosage, postoperative mechanical ventilation duration, the length of ICU and hospital stay, and perioperative CVP might be the risk factors of AKI after operation. Multivariate Logistic regression analysis showed that preoperative PASP was one of independent risk factors for AKI in patients undergoing CPB heart surgery [odds ratio (OR) = 4.753, 95% confidence interval (95%CI) was 1.328-8.417, P = 0.004]. The incidence of AKI after operation in PASP ≥ 60 mmHg group was significantly higher than that in < 60 mmHg group [73.8% (712/965) vs. 35.3% (1 880/5 320), P < 0.01]. (2) After a follow-up of (11±3) months, 237 patients (3.8%) died in 6 285 patients. The mortality of patients in PASP ≥ 60 mmHg group was significantly higher than that in < 60 mmHg group [9.5% (92/965) vs. 2.7% (145/5 320), P < 0.01]. Kaplan-Meier survival curve analysis showed that there was a significant difference between the two groups in cumulative survival rate (Log-Rank test: χ2 = 144.400, P < 0.001). Univariate analysis showed that male, age, preoperative hypertension, ejection fraction, PASP, intraoperative CPB duration, aortic occlusion duration, fluid balance, epinephrine dosage, postoperative mechanical ventilation duration, the length of ICU and hospital stay, and perioperative CVP might be risk factors for long-term death of patients undergoing CPB heart surgery. Multivariate Cox regression analysis showed that for every 1 mmHg increase in preoperative PASP, the long-term mortality increased by 1.126 times [hazard ratio (HR) = 1.126, 95%CI was 1.003-1.604, P = 0.021]. CONCLUSIONS: The increase of PASP is related to AKI after CPB heart surgery, which is an independent risk factor for long-term mortality.


Assuntos
Injúria Renal Aguda/diagnóstico , Pressão Sanguínea , Ponte Cardiopulmonar , Injúria Renal Aguda/sangue , Humanos , Complicações Pós-Operatórias , Prognóstico , Artéria Pulmonar , Estudos Retrospectivos , Fatores de Risco
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