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1.
Sci Total Environ ; 751: 141726, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32889464

RESUMO

Ultrafine particles (UFPs) are of concern because of their high pulmonary deposition efficiency. However, present control measures are generally targeted at fine particles (PM2.5), with little effect on UFPs. The health effects of UFPs at different PM2.5 concentrations may provide a basic for controlling UFPs but remain unclear in polluted areas. School children spend the majority of their time in the classrooms. This study investigated the different short-term effects of indoor UFPs on school children in Beijing, China when indoor PM2.5 concentrations exceeded or satisfied the recently published Chinese standard for indoor PM2.5. Cardiopulmonary functions of 48 school children, of whom 46 completed, were measured three times. Indoor PM2.5 and UFPs were monitored in classrooms on weekdays. Measurements were separated into two groups according to the abovementioned standard. Mixed-effect models were used to explore the health effects of the air pollutants. Generally, UFP-associated effects on children's cardiopulmonary function persisted even at relatively low PM2.5 concentrations, especially on heart rate variability indices. The risks associated with high PM2.5 concentrations are well-known, but the effects of UFPs on children's cardiopulmonary function deserve more attention even when PM2.5 has been controlled. UFP control and standard setting should therefore be considered.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Pequim , Criança , China , Monitoramento Ambiental , Humanos , Tamanho da Partícula , Material Particulado/efeitos adversos , Material Particulado/análise
2.
Int J Mol Sci ; 21(21)2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33142808

RESUMO

Polyethylene glycol (PEG) coating of gold nanoparticles (AuNPs) improves AuNP distribution via blood circulation. The use of PEG-coated AuNPs was shown to result in acute injuries to the liver, kidney, and spleen, but long-term toxicity has not been well studied. In this study, we investigated reporter induction for up to 90 days in NF-κB transgenic reporter mice following intravenous injection of PEG-coated AuNPs. The results of different doses (1 and 4 µg AuNPs per gram of body weight), particle sizes (13 nm and 30 nm), and PEG surfaces (methoxyl- or carboxymethyl-PEG 5 kDa) were compared. The data showed up to 7-fold NF-κB reporter induction in mouse liver from 3 h to 7 d post PEG-AuNP injection compared to saline-injected control mice, and gradual reduction to a level similar to control by 90 days. Agglomerates of PEG-AuNPs were detected in liver Kupffer cells, but neither gross pathological abnormality in liver sections nor increased activity of liver enzymes were found at 90 days. Injection of PEG-AuNPs led to an increase in collagen in liver sections and elevated total serum cholesterol, although still within the normal range, suggesting that inflammation resulted in mild fibrosis and affected hepatic function. Administrating PEG-AuNPs inevitably results in nanoparticles entrapped in the liver; thus, further investigation is required to fully assess the long-term impacts by PEG-AuNPs on liver health.

3.
J Agric Food Chem ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226223

RESUMO

Nowadays consumers are increasingly demanding food with fewer synthetic preservatives, which makes antimicrobial essential oils (EOs) from plants promising alternatives. In this work, surfactant-free emulsions were successfully fabricated from Cinnamon cassia oil (C. cassia oil) with partially deacetylated chitin nanofiber (ChNF) adopted as a Pickering stabilizer. The storage stability and microstructures of the emulsions with different concentrations of ChNF were studied in detail. As ChNF concentration increased, the emulsion droplet size decreased while the emulsion stability increased with stable periods as long as 90 days. This could be attributed to the Pickering stabilization realized by irreversible adsorption of the ChNF at the oil-water interface (revealed by fluorescent microscopy) and subsequent formation of an interdroplet ChNF network in the continuous phase, which was further strengthened in the presence of the aldehyde moiety in the C. cassia oil (verified by FTIR spectra). The rheological data and SEM images provided further evidence for network formation in the emulsions with increased ChNF concentration. Furthermore, the antimicrobial activity of the emulsion against Escherichia coli and the release patterns of EOs from emulsions were also investigated. The emulsions showed prolonged antibacterial activities but enhanced diffusion efficiency with the introduction of ChNF, which turned out to be a good encapsulation system for the controlled release of EOs. This work evidences the promising advantages of ChNF-stabilized Pickering emulsions as a facile EOs delivery system for application in food preservation and related fields.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33206602

RESUMO

In this paper, a recurrent neural network is designed for video saliency prediction considering spatial-temporal features. In our work, video frames are routed through the static network for spatial features and the dynamic network for temporal features. For the spatial-temporal feature integration, a novel select and re-weight fusion model is proposed which can learn and adjust the fusion weights based on the spatial and temporal features in different scenes automatically. Finally, an attention-aware convolutional long short term memory (ConvLSTM) network is developed to predict salient regions based on the features extracted from consecutive frames and generate the ultimate saliency map for each video frame. The proposed method is compared with state-of-the-art saliency models on five public video saliency benchmark datasets. The experimental results demonstrate that our model can achieve advanced performance on video saliency prediction.

5.
Eur J Neurol ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175469

RESUMO

BACKGROUND AND PURPOSE: The aim of this meta-analysis study was to assess the predictive effects of RNF213 p.R4810K on phenotype in MMD. METHODS: Electronic databases (Pubmed, EMBASE, etc) were searched and the relevant articles (published till August 2020) were retrieved. Review Manage 5.3 and Stata 12.0 were applied to complete all statistical analyses. Pooled odds ratios (ORs), 95% confidence intervals (CIs), and three comparison models were evaluated to analyze the association using a fixed-effect model. RESULTS: A total of 2798 patients with MMD were selected and the effects of heterozygous or homozygous RNF213 p.R4810K on 18 clinical features were identified. The patients of under 15 years were more common in GA and AA groups (AA vs GA: P = 0.009; AA vs GG: P = 0.003; GA vs GG: P = 0.001). Of homozygotes, the most affected MMD before age 4 (AA vs GA: P < 0.00001; AA vs GG: P < 0.00001). The frequency of infarctions and transient ischemic attack was significantly higher in homozygotes or heterozygotes. However, the frequency of intracerebral/intraventricular hemorrhage was lower in patients with the GA than GG genotype. More patients with MMD having a family history of the disease with AA and GA genotypes (P = 0.003, P < 0.00001, respectively). Posterior cerebral artery involvement was more common in GA patients (P < 0.00001). CONCLUSION: The homozygous or heterozygous RNF213 may be an efficient biomarker to classify different clinical phenotypes of MMD.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33170305

RESUMO

Atmospheric particulate matters in nine size fractions were sampled at Huangshi city, Hubei province. Elemental concentrations occurred unimodal size distribution for Zn, Pb and Ni, dimodal distribution for Ca, S, Fe and Ti, and trimodal distribution for Cl, K, Mn, Cu and Cr. Enrichment factor and principal component analysis identified the main sources from crustal material, biomass burning, waste incineration, vehicular and industrial emission. As for the non-carcinogenic health risk through inhalation, there were certain potential risks for Mn and Sb for children, and Pb for children and adults in PM2.5. It showed certain potential risks for Mn, Sb and Pb for children and adults in PM10. As for the carcinogenic health risk through inhalation, Cr in PM2.5 and Ni, Co and Cr in PM10 indicated unacceptable risk for children and adults. Meanwhile, Co and Ni in PM2.5 represented acceptable risk for children.

8.
Biomed Res Int ; 2020: 9708324, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224986

RESUMO

OVATE family proteins (OFPs) are plant-specific transcription factors that play important roles in plant development. Although common wheat (Triticum aestivum L.) is a major staple food worldwide, OFPs have not been systematically analyzed in this important crop. Here, we performed a genome-wide survey of OFP genes in wheat and identified 100 genes belonging to 34 homoeologous groups. Arabidopsis thaliana, rice (Oryza sativa), and wheat OFP genes were divided into four subgroups based on their phylogenetic relationships. Structural analysis indicated that only four TaOFPs contain introns. We mapped the TaOFP genes onto the wheat chromosomes and determined that TaOFP17 was duplicated in this crop. A survey of cis-acting elements along the promoter regions of TaOFP genes suggested that subfunctionalization of homoeologous genes might have occurred during evolution. The TaOFPs were highly expressed in wheat, with tissue- or organ-specific expression patterns. In addition, these genes were induced by various hormone and stress treatments. For instance, TaOPF29a-A was highly expressed in roots in response to drought stress. Wheat plants overexpressing TaOPF29a-A had longer roots and higher dry weights than nontransgenic plants under drought conditions, suggesting that this gene improves drought tolerance. Our findings provide a starting point for further functional analysis of this important transcription factor family and highlight the potential of using TaOPF29a-A to genetically engineer drought-tolerant crops.

9.
J Chemother ; : 1-11, 2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33164721

RESUMO

Abnormal expression of ADAM29 has been frequently reported in several cancers, however, its role in clear cell renal cell carcinoma (ccRCC) has not evaluated in detail. Herein, we attempt to determine the biological role and the action mechanism of ADAM29 in ccRCC. Bioinformatics analysis based on the ccRCC RNA-Seq dataset from TCGA database revealed that ADAM29 was up-expressed in ccRCC tissues by comparison with normal tissues. And a significant increase of ADAM29 expression was also observed in 3 ccRCC cell lines (UT33A, Caki-1, and786-O) in comparison with normal cell line. Besides, high level of ADAM29 was found to be connected with the poor prognosis and could be considered as an independent prognosticator for patients with ccRCC. Furthermore, functional experiments in vitro demonstrated that ADAM29 promoted the growth, invasion and migration of ccRCC cells. Moreover, Western blot assays indicated that ADAM29 was positively correlated with the level of proliferation-related proteins Cyclin D1 and PCNA and motion-related proteins MMP9 and Snail. Our data indicate that ADAM29 acts as an oncogene that increases tumour cells proliferation, invasion and migration partly by regulating the expression of Cyclin D1/PCNA/MMP9/Snail, suggesting that ADAM29 may become a prognosticator and therapeutic candidate for ccRCC.

10.
J Exp Clin Cancer Res ; 39(1): 229, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33121524

RESUMO

BACKGROUND: Dysregulation of long non-coding RNAs (lncRNAs) is responsible for cancer initiation and development, positioning lncRNAs as not only biomarkers but also promising therapeutic targets for cancer treatment. A growing number of lncRNAs have been reported in hepatocellular carcinoma (HCC), but their functional and mechanistic roles remain unclear. METHODS: Gene Set Enrichment Analysis was used to investigate the molecular mechanism of UPK1A antisense RNA 1 (UPK1A-AS1). Cell Counting Kit-8 assays, EdU assays, flow cytometry, western blotting, and xenograft assays were used to confirm the role of UPK1A-AS1 in the proliferation of HCC cells in vitro and in vivo. Bioinformatics analyses and quantitative polymerase chain reaction (qRT-PCR) were performed to explore the interplay between UPK1A-AS1 and enhancer of zeste homologue 2 (EZH2). RNA immunoprecipitation (RIP), RNA pull-down assays, western blotting, and qRT-PCR were conducted to confirm the interaction between UPK1A-AS1 and EZH2. The interaction between UPK1A-AS1 and miR-138-5p was examined by luciferase reporter and RIP assays. Finally, the expression level and prognosis value of UPK1A-AS1 in HCC were analyzed using RNA sequencing data from The Cancer Genome Atlas datasets. RESULTS: We showed that UPK1A-AS1, a newly identified lncRNA, promoted cellular proliferation and tumor growth by accelerating cell cycle progression. Cell cycle-related genes, including CCND1, CDK2, CDK4, CCNB1, and CCNB2, were significantly upregulated in HCC cells overexpressing UPK1A-AS1. Furthermore, overexpression of UPK1A-AS1 could protect HCC cells from cis-platinum toxicity. Mechanistically, UPK1A-AS1 interacted with EZH2 to mediate its nuclear translocation and reinforce its binding to SUZ12, leading to increased H27K3 trimethylation. Targeting EZH2 with specific small interfering RNA impaired the UPK1A-AS1-mediated upregulation of proliferation and cell cycle progression-related genes. Moreover, miR-138-5p was identified as a direct target of UPK1A-AS1. Additionally, UPK1A-AS1 was significantly upregulated in HCC, and the upregulation of UPK1A-AS1 predicted poor prognosis for patients with HCC. CONCLUSIONS: Our study revealed that UPK1A-AS1 promotes HCC development by accelerating cell cycle progression through interaction with EZH2 and sponging of miR-138-5p, suggesting that UPK1A-AS1 possesses substantial potential as a novel biomarker for HCC prognosis and therapy.

11.
Ann Emerg Med ; 76(6): 730-738, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33010956

RESUMO

STUDY OBJECTIVE: Falls are a major cause of mortality and morbidity in adults aged 65 years and older and a common chief complaint in the emergency department (ED). However, the rate of missed opportunities to diagnose and intervene in modifiable fall-risk factors in the ED is unknown. We hypothesize that although ED providers (defined as ED attendings, residents, and advanced care providers) excel at assessing and ruling out injury, they miss the opportunity to identify a large portion of the modifiable risk factors that contribute to a patient's fall. Our objective is to quantify the number of missed opportunities to identify and reduce fall-risk factors in older adult ED patients presenting after a fall. METHODS: This secondary analysis used data from a prospective cohort study of older patients at a single academic urban ED. The original study investigated the standard ED evaluation after a fall in older adults. All patients in the original study had a falls evaluation conducted at their ED visit by trained research assistants; this served as the standard fall evaluation. We reviewed the charts of study patients and identified modifiable fall-risk factors. We then determined the number of missed opportunities to intervene in these risk factors during the ED encounter; the primary outcome was the percentage of missed opportunities to identify risk factors in older ED patients who fell. RESULTS: We found that of the 400 patient charts reviewed, 349 patients had a modifiable risk factor for falling. Of those patients with known modifiable risk factors, the ED team missed identifying the factors in 335 patients (96%). The most commonly missed fall-risk factors were visual acuity (147/154; 96%) and the use of high-risk medications (245/259;95%). Gait abnormalities had the lowest rates of missed modifiable risk factors, at 56% of patients (109/196). When a modifiable risk factor was identified and intervened in, it was most commonly done in the ED observation unit by a physician or physical therapist, and often consisted of an outpatient referral or primary care physician follow-up. CONCLUSION: Providers frequently fail to identify and intervene in modifiable fall-risk factors in older adult patients presenting to the ED after a fall; this is a missed opportunity. Addressing the risk factors that contributed to the fall during a fall-related ED visit may minimize fall risk and promote safer mobility.

12.
JCI Insight ; 5(22)2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33035201

RESUMO

Rapid and specific antibody testing is crucial for improved understanding, control, and treatment of COVID-19 pathogenesis. Herein, we describe and apply a rapid, sensitive, and accurate virus neutralization assay for SARS-CoV-2 antibodies. The assay is based on an HIV-1 lentiviral vector that contains a secreted intron Gaussia luciferase (Gluc) or secreted nano-luciferase reporter cassette, pseudotyped with the SARS-CoV-2 spike (S) glycoprotein, and is validated with a plaque-reduction assay using an authentic, infectious SARS-CoV-2 strain. The assay was used to evaluate SARS-CoV-2 antibodies in serum from individuals with a broad range of COVID-19 symptoms; patients included those in the intensive care unit (ICU), health care workers (HCWs), and convalescent plasma donors. The highest neutralizing antibody titers were observed among ICU patients, followed by general hospitalized patients, HCWs, and convalescent plasma donors. Our study highlights a wide phenotypic variation in human antibody responses against SARS-CoV-2 and demonstrates the efficacy of a potentially novel lentivirus pseudotype assay for high-throughput serological surveys of neutralizing antibody titers in large cohorts.

13.
J Environ Manage ; 278(Pt 1): 111479, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33126192

RESUMO

In last two decades, the number of detected activated pharmaceutical ingredients (APIs) in the natural environment worldwide has increased due to their widespread use in daily life. However, given the large number of APIs that are currently in use (approximate 850 are on the market in China), it is impractical to investigate the occurrence, ecotoxicological effects, and perform environmental risk assessment for all drugs. Therefore, it is crucial to rank and prioritize APIs in the environment to identify the compounds of high concern. In China, since information on API usage is not available, an attempt was made to use the number of products per API (the number of pharmaceutical commodities that contain a particular API) on the market multiplied by its daily dose (average daily dose of medication for adults used for the primary therapeutic purpose) to replace the usage in the exposure modeling. Coupled with the hazard assessment, including acute and chronic toxicity of aquatic ecological effects and potential effects related to the therapeutic mode of action, risk scores were estimated and used for ranking. Application of the approach was illustrated for 259 APIs with product number no less than 4. A list of 20 APIs was finally identified as a potential priority, including drugs of cardiovascular, nervous system, respiratory system, musculoskeletal system and antibiotics. In the future, this approach could be applied to prioritize APIs in other countries/regions where information on API usage are limited or non-existent.

14.
Environ Toxicol ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33107671

RESUMO

Prostate cancer osteoblastic bone metastases are incurable and associated with chronic bone pain and a high mortality rate. Osteoclast-targeting drugs intended to prevent skeletal-related events associated with prostate cancer bone metastases do not prolong overall survival. Improved understanding of the bone-derived factors that contribute to prostate cancer osteoblastic bone metastases is required to design treatments that will improve morbidities and overall survival. Activated osteoblasts stimulate prostate cancer growth in bone. In this study, we report that prostate cancer conditioned medium (CM) promoted bone morphogenetic protein (BMP)-2, -4 and -7 production and the expression of osteogenic transcription factors Runx2 and osterix in osteoblasts. Treating the prostate cancer CM with antibody against CCN3 (nephroblastoma-overexpressed), a cysteine-rich protein that belongs to the CCN family, reduced all of these increases. Incubation of osteoblasts with CCN3 facilitated phosphorylation of GSK3ß and ß-catenin. GSK3ß and ß-catenin inhibitors or siRNAs all abolished CCN3-induced promotion of BMPs, Runx2 and osterix expression in osteoblasts. Our results indicate that prostate cancer-secreted CCN3 enhances BMP, Runx2 and osterix expression in osteoblasts via the GSK3ß and ß-catenin signaling pathways. This understanding of the role played by CCN3 in osteoblastic prostate bone metastasis may lead to more efficient targeted therapies.

15.
Am J Emerg Med ; 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-33041131

RESUMO

INTRODUCTION: The importance of this study is to devise an efficient tool for assessing frailty in the ED. The goals of this study are 1) to correlate ultrasonographic (US) measurements of muscle thickness in older ED patients with frailty and 2) to correlate US-measured sarcopenia with falls, subsequent hospitalizations and ED revisits. METHODS: Participants were conveniently sampled from a single ED in this prospective cohort pilot study of patients aged 65 or older. Participants completed a Fatigue, Resistance, Ambulation, Illness and Loss of Weight (FRAIL) scale assessment and US measurements of their upper arm muscles, quadricep muscles, and abdominal wall muscles thickness. We conducted one-month follow-up phone calls to assess for falls, ED revisits, and subsequent hospital visits. RESULTS: We enrolled 43 patients (mean age of 78.5). Ultrasound measurements of the three muscle groups were not significantly different between frail and non-frail groups. Frail participants had greater bicep asymmetry (a difference of 0.47 cm vs 0.24 cm, p < .01). A predictive logistic regression model using average quadriceps thickness and biceps asymmetry was found to identify frail patients (AUC of 0.816). Participants with subsequent falls had smaller quadriceps (1.18 cm smaller, p < .01). Subsequently hospitalized patients were found to have smaller quadriceps muscles (0.54 cm smaller, p = .03) and abdominal wall muscles (0.25 cm smaller, p = .01). CONCLUSION: US measurements of sarcopenia in older patients had mild to moderate associations with frailty, falls and subsequent hospitalizations. Further investigation is needed to confirm these findings.

16.
Neurosci Lett ; 738: 135339, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32882317

RESUMO

Our previous study showed that PI3Kγ inhibition with AS605240 plus a standard rat-dose tPA (10 mg/kg) combination attenuates delayed tPA-induced brain hemorrhage and ameliorates acute stroke injury 3 days after ischemic stroke in rats. The purpose of this study was to investigate whether combining AS605240 with tPA can enhance thrombolytic efficacy, so that lower doses of tPA can be applied to improve long-term outcome after ischemic stroke. The results showed that AS605240 plus low-dose tPA (5 mg/kg) combination therapy at 4 h after stroke onset significantly reduced infarct volume and neurological deficits at 24 h after stroke compared with saline, AS605240 or low-dose tPA alone group. Importantly, the combination therapy significantly reduced the delayed tPA-associated brain hemorrhage. Moreover, the combination therapy significantly decreased the size of the residual embolus within the middle cerebral artery, which was associated with a decrease in plasma plasminogen activator inhibitor-1 (PAI-1) activity compared with saline and tPA alone. Finally, AS605240 plus low-dose tPA combination improved long-term outcome for at least 35 days after stroke compared with the saline-treated group. Taken together, these findings suggest that PI3Kγ inhibition with AS605240 might act as an adjunct approach for enhancing tPA thrombolytic efficacy in acute ischemic stroke.

17.
Aging (Albany NY) ; 12(18): 18635-18648, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32991325

RESUMO

Pathophysiological events that modulate the progression of structural changes in osteoarthritis (OA) include monocyte adhesion and infiltration, and synovial inflammation. In particular, the adhesion protein intercellular adhesion molecule type 1 (ICAM-1) promotes monocyte recruitment into the synovial tissue. Visfatin is an adipocyte hormone that promotes the release of inflammatory cytokines during OA progression. We report that visfatin enhances ICAM-1 expression in human OA synovial fibroblasts (OASFs) and facilitates the adhesion of monocytes with OASFs. AMPK and p38 inhibitors, as well as their respective siRNAs, attenuated the effects of visfatin upon ICAM-1 synthesis and monocyte adhesion. We also describe how miR-320a negatively regulates visfatin-induced promotion of ICAM-1 expression and monocyte adhesion. We detail how visfatin affects ICAM-1 expression and monocyte adhesion with OASFs by inhibiting miR-320a synthesis via the AMPK and p38 signaling pathways.

18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(10): 1084-1086, 2020 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-32924106

RESUMO

OBJECTIVE: To carry out prenatal diagnosis on a fetus with abnormal findings by ultrasonography and non-invasive prenatal testing. METHODS: The fetus and both parents were subjected to chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) analysis. RESULTS: The karyotypes of both parents were normal. The fetus carried a 46,N,der(X;16)(q28;q22) unbalanced translocation. SNP-array analysis confirmed that the derived chromosomal fragment of the fetus has originated from 16q. The fetus was diagnosed with 16q partial trisomy syndrome. CONCLUSION: Combined chromosomal karyotyping analysis and SNP-array can detect chromosomal aberrations at submicroscopic level and enable accurate diagnosis of the fetus.


Assuntos
Transtornos Cromossômicos , Diagnóstico Pré-Natal/métodos , Trissomia , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 16 , Feminino , Feto , Humanos , Cariotipagem , Gravidez , Trissomia/diagnóstico , Trissomia/genética , Ultrassonografia
19.
Toxicol Appl Pharmacol ; 407: 115252, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32987027

RESUMO

Acute lung injury (ALI) is a severe disease for which effective drugs are still lacking at present. Forsythia suspensa is a traditional Chinese medicine commonly used to relieve respiratory symptoms in China, but its functional mechanisms remain unclear. Therefore, forsythoside A (FA), the active constituent of F. suspensa, was studied in the present study. Inflammation models of type II alveolar epithelial MLE-12 cells and BALB/c mice stimulated by lipopolysaccharide (LPS) were established to explore the effects of FA on ALI and the underlying mechanisms. We found that FA inhibited the production of monocyte chemoattractant protein-1 (MCP-1/CCL2) in LPS-stimulated MLE-12 cells in a dose-dependent manner. Moreover, FA decreased the adhesion and migration of monocytes to MLE-12 cells. Furthermore, miR-124 expression was upregulated after FA treatment. The luciferase report assay showed that miR-124 mimic reduced the activity of CCL2 in MLE-12 cells. However, the inhibitory effects of FA on CCL2 expression and monocyte adhesion and migration to MLE-12 cells were counteracted by treatment with a miR-124 inhibitor. Critically, FA ameliorated LPS-induced pathological damage, decreased the serum levels of tumor necrosis factor-α and interleukin-6, and inhibited CCL2 secretion and macrophage infiltration in lungs in ALI mice. Meanwhile, administration of miR-124 inhibitor attenuated the protective effects of FA. The present study suggests that FA attenuates LPS-induced adhesion and migration of monocytes to type II alveolar epithelial cells though upregulating miR-124, thereby inhibiting the expression of CCL2. These findings indicate that the potential application of FA is promising and that miR-124 mimics could also be used in the treatment of ALI.

20.
J Fluoresc ; 30(6): 1357-1364, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32870455

RESUMO

Cysteine (Cys) is an important endogenous amino acid and plays critical physiological roles in living systems. Herein, an endoplasmic reticulum (ER)-targeting fluorescent probe (FER-Cys) was designed and prepared for imaging of Cys in living cells. The probe FER-Cys consists of a fluorescein framework as the fluorescent platform, acrylate group as the response site for the selective recognition of Cys, and ER-specific p-toluenesulfonamide fragment. After the response of probe FER-Cys to Cys, a turn-on fluorescence signal at 546 nm could be detected obviously. The probe FER-Cys further shows desirable selectivity to Cys. Finally, the probe FER-Cys was proven to selectively detect Cys in live cells and successfully image the changes of Cys level in the cell models of H2O2-induced redox imbalance.

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